<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT01709305</url>
  </required_header>
  <id_info>
    <org_study_id>0431-313</org_study_id>
    <nct_id>NCT01709305</nct_id>
  </id_info>
  <brief_title>A Study of the Safety and Efficacy of Glimepiride, Gliclazide, Repaglinide or Acarbose When Added to Sitagliptin + Metformin Combination Therapy in Chinese Participants With Diabetes (MK-0431-313)</brief_title>
  <official_title>A Multicenter, Randomized, Active-Controlled, Open-label Clinical Trial to Evaluate the Safety and Efficacy of Glimepiride, Gliclazide, Repaglinide or Acarbose as a Third OAHA on Top of Sitagliptin+Metformin Combination Therapy in Chinese Patients With Type 2 Diabetes Mellitus</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Merck Sharp &amp; Dohme LLC</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Merck Sharp &amp; Dohme LLC</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      To assess the effect of adding acarbose or repaglinide or gliclazide to sitagliptin plus&#xD;
      metformin, compared to adding glimepiride, on glycemic improvements in Type 2 Diabetes&#xD;
      Mellitus (T2DM) participants who require the addition of a third oral anti-hyperglycemic&#xD;
      agent (OAHA) according to China Guideline for Type 2 Diabetes. The three co-primary&#xD;
      hypotheses are that after 24 weeks of treatment in phase 2, the mean change from baseline in&#xD;
      hemoglobin A1c (A1c) in participants receiving either (1)acarbose or (2)repaglinide or&#xD;
      (3)gliclazide added to sitagliptin and metformin combination is non-inferior to that of&#xD;
      participants receiving glimepiride added to sitagliptin and metformin combination. The study&#xD;
      would be declared successful if at least one of the three primary hypotheses was met.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Participants coming on study will be stabilized to a standardized metformin dose: this may&#xD;
      take about 10 weeks, and then combination therapy with metformin + sitagliptin will begin&#xD;
      during Phase 1 (Week 0 through Week 20). If a participant has already been on a stabilized&#xD;
      metformin dose, they will start immediately on combination therapy with metformin +&#xD;
      sitagliptin for 20 weeks (Phase 1).&#xD;
&#xD;
      In Phase 2, participants who have failed to achieve adequate glycemic control (A1c ≥ 7% and ≤&#xD;
      10% at Week 16 and fasting finger stick glucose ≥130 mg/dL and ≤280 mg/dL at Week 20) will be&#xD;
      randomized to receive add-on therapy with glimepiride, repaglinide, acarbose, or gliclazide&#xD;
      for 24 weeks (Week 20 through Week 44).&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">November 8, 2012</start_date>
  <completion_date type="Actual">April 17, 2015</completion_date>
  <primary_completion_date type="Actual">April 17, 2015</primary_completion_date>
  <phase>Phase 4</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change From Phase 2 Baseline to Week 44 in Hemoglobin A1c (HbA1c) Levels (Phase 2)</measure>
    <time_frame>Phase 2 Baseline (Week 20) and Week 44</time_frame>
    <description>HbA1c is blood marker used to report average blood glucose levels over prolonged periods of time and is reported as a percentage (%). Change from baseline reflects the Week 44 A1C minus baseline A1C. Baseline is defined as Visit 6/Week 20. If this measurement was unavailable, the Week 16 value was used. Change from baseline was based on the constrained longitudinal data analysis (cLDA) model including all available measurements from baseline through the last visit. The terms in the cLDA model include treatment, time in weeks (categorical), regions, and treatment-by-time interaction.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change From Phase 2 Baseline to Week 44 in Participant Body Weight (Phase 2)</measure>
    <time_frame>Phase 2 Baseline (Week 20), Week 44</time_frame>
    <description>Change from baseline in body weight in Phase 2 was reported. Change from baseline reflects the Week 44 body weight minus baseline body weight. Baseline is defined as Visit 6/Week 20. If this measurement was unavailable, the Week 16 value was used.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Participants With Hypoglycemia Events (Phase 2)</measure>
    <time_frame>From Week 20 through Week 44</time_frame>
    <description>Hypoglycemia events represent epidsodes symptomatic of hypoglycemia (e.g., weakness, dizziness, shakiness, increased sweating, palpitations, or confusion) and/or finger stick glucose values of ≤70 mg/dL (3.9 mmol/L). The percentage of participants with hypoglycemia events was reported.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Participants With a Gastrointestinal (GI) AE of Nausea (Phase 2)</measure>
    <time_frame>From Week 20 through Week 44</time_frame>
    <description>The percentage of participants with a GI AE of &quot;nausea&quot; was reported.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Participants With a GI AE of Vomiting (Phase 2)</measure>
    <time_frame>From Week 20 through Week 44</time_frame>
    <description>The percentage of participants with a GI AE of &quot;vomiting&quot; was reported.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Participants With a GI AE of Diarrhea (Phase 2)</measure>
    <time_frame>From Week 20 through Week 44</time_frame>
    <description>The percentage of participants with a GI AE of &quot;diarrhea&quot; was reported.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Percentage of Participants With a GI AE of Abdominal Pain (Phase 2)</measure>
    <time_frame>From Week 20 through Week 44</time_frame>
    <description>The percentage of participants with a GI AE of &quot;abdominal pain&quot; was reported.</description>
  </secondary_outcome>
  <number_of_arms>4</number_of_arms>
  <enrollment type="Actual">5570</enrollment>
  <condition>Type 2 Diabetes Mellitus</condition>
  <arm_group>
    <arm_group_label>Metformin + Sitagliptin + Glimepiride</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>During Phase 2, participants receive up to 6 mg glimepiride daily as an add-on to metformin + sitagliptin combination therapy for 24 weeks (Week 20 through Week 44).</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Metformin + Sitagliptin + Repaglinide</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>During Phase 2, participants receive up to 16 mg repaglinide daily as an add-on to metformin + sitagliptin combination therapy for 24 weeks (Week 20 through Week 44).</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Metformin + Sitagliptin + Acarbose</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>During Phase 2, participants receive 50-100 mg acarbose three times daily as an add-on to metformin + sitagliptin combination therapy for 24 weeks (Week 20 through Week 44).</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Metformin + Sitagliptin + Gliclazide</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>During Phase 2, participants receive 30-120 mg gliclazide daily as an add-on to metformin + sitagliptin combination therapy for 24 weeks (Week 20 through Week 44).</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Metformin</intervention_name>
    <description>Metformin, 500 mg or 850 mg oral tablets, twice or three times a day (BID or TID) for a total dose of at least 1500 mg daily; administered with food.</description>
    <arm_group_label>Metformin + Sitagliptin + Acarbose</arm_group_label>
    <arm_group_label>Metformin + Sitagliptin + Gliclazide</arm_group_label>
    <arm_group_label>Metformin + Sitagliptin + Glimepiride</arm_group_label>
    <arm_group_label>Metformin + Sitagliptin + Repaglinide</arm_group_label>
    <other_name>Fortamet®</other_name>
    <other_name>Glucophage®</other_name>
    <other_name>Glucophage® XR</other_name>
    <other_name>Glumetza®</other_name>
    <other_name>Riomet®</other_name>
    <other_name>Metgluco®</other_name>
    <other_name>Glycoran®</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Sitagliptin</intervention_name>
    <description>Sitagliptin, 100 mg oral tablet, once daily (QD); administered with or without food</description>
    <arm_group_label>Metformin + Sitagliptin + Acarbose</arm_group_label>
    <arm_group_label>Metformin + Sitagliptin + Gliclazide</arm_group_label>
    <arm_group_label>Metformin + Sitagliptin + Glimepiride</arm_group_label>
    <arm_group_label>Metformin + Sitagliptin + Repaglinide</arm_group_label>
    <other_name>Januvia®</other_name>
    <other_name>Tesavel®</other_name>
    <other_name>Xelevia®</other_name>
    <other_name>Ristaben®</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Acarbose</intervention_name>
    <description>Acarbose, 50 mg oral tablets, TID (150 mg total daily dose); administered with the first bite of each main meal.</description>
    <arm_group_label>Metformin + Sitagliptin + Acarbose</arm_group_label>
    <other_name>Precose®</other_name>
    <other_name>Glucobay™</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Repaglinide</intervention_name>
    <description>Repaglinide, 0.5 mg and/or 1 mg oral tablets, TID (up to 16 mg daily); administered within 30 minutes of each meal.</description>
    <arm_group_label>Metformin + Sitagliptin + Repaglinide</arm_group_label>
    <other_name>Prandin®</other_name>
    <other_name>Fulaidi™</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Glimepiride</intervention_name>
    <description>Glimepiride, 1 mg and/or 2 mg oral tablets, QD (up to 6 mg daily); administered before the first main meal of the day</description>
    <arm_group_label>Metformin + Sitagliptin + Glimepiride</arm_group_label>
    <other_name>Amaryl®</other_name>
    <other_name>Glimy</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Gliclazide</intervention_name>
    <description>Gliclazide, 30 mg oral tablets, QD or BID (30 mg to 120 mg total daily dose); administered with meal.</description>
    <arm_group_label>Metformin + Sitagliptin + Gliclazide</arm_group_label>
    <other_name>Diamicron MR™</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Has Type 2 Diabetes Mellitus;&#xD;
&#xD;
          -  Agrees to use an effective method of contraception or must not otherwise be at risk of&#xD;
             becoming pregnant (female participants).&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Has a history of type 1 diabetes mellitus or a history of ketoacidosis;&#xD;
&#xD;
          -  Has been treated with insulin, a dipeptidyl peptidase 4 (DPP-4) inhibitor, a&#xD;
             Glucagon-like peptide-1 (GLP-1) mimetic or analogue before;&#xD;
&#xD;
          -  Is on a weight loss program (not in maintenance phase), has started a weight loss&#xD;
             medication, or has undergone bariatric surgery within 12 months;&#xD;
&#xD;
          -  Has undergone a surgical procedure within 4 weeks;&#xD;
&#xD;
          -  Has had new or worsening signs or symptoms of coronary heart disease or congestive&#xD;
             heart failure within past 3 months, or has acute coronary syndrome, coronary artery&#xD;
             intervention, or stroke or transient ischemic neurological disorder;&#xD;
&#xD;
          -  Has a medical history of active liver disease, including chronic active hepatitis B or&#xD;
             C, primary biliary cirrhosis, or symptomatic gallbladder disease;&#xD;
&#xD;
          -  Has poorly controlled hypertension;&#xD;
&#xD;
          -  Has severe peripheral vascular disease;&#xD;
&#xD;
          -  Has human immunodeficiency virus (HIV);&#xD;
&#xD;
          -  Has had a clinically important hematological disorder;&#xD;
&#xD;
          -  Routinely consumes &gt;2 alcoholic drinks per day or &gt;14 alcoholic drinks per week, or&#xD;
             engages in binge drinking;&#xD;
&#xD;
          -  Has a history of intolerance or hypersensitivity or any contraindication to study&#xD;
             medications (including sitagliptin, metformin, glimepiride, repaglinide, acarbose or&#xD;
             gliclazide) based upon the Chinese label;&#xD;
&#xD;
          -  Is on or likely to require treatment with ≥2 consecutive weeks or repeated courses of&#xD;
             pharmacologic doses of corticosteroids (other than inhaled, nasal, or topical&#xD;
             corticosteroids);&#xD;
&#xD;
          -  Is pregnant or breast feeding or is expecting to conceive or donate eggs during the&#xD;
             study, including 14 days following the last dose of study drug (female participants).&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>75 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Medical Director</last_name>
    <role>Study Director</role>
    <affiliation>Merck Sharp &amp; Dohme LLC</affiliation>
  </overall_official>
  <removed_countries>
    <country>China</country>
  </removed_countries>
  <results_reference>
    <citation>Xu W, Mu Y, Zhao J, Zhu D, Ji Q, Zhou Z, Yao B, Mao A, Engel SS, Zhao B, Bi Y, Zeng L, Ran X, Lu J, Ji L, Yang W, Jia W, Weng J. Efficacy and safety of metformin and sitagliptin based triple antihyperglycemic therapy (STRATEGY): a multicenter, randomized, controlled, non-inferiority clinical trial. Sci China Life Sci. 2017 Mar;60(3):225-238. doi: 10.1007/s11427-016-0409-7. Epub 2017 Feb 7.</citation>
    <PMID>28271251</PMID>
  </results_reference>
  <verification_date>July 2018</verification_date>
  <study_first_submitted>October 16, 2012</study_first_submitted>
  <study_first_submitted_qc>October 16, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 18, 2012</study_first_posted>
  <results_first_submitted>April 6, 2016</results_first_submitted>
  <results_first_submitted_qc>April 6, 2016</results_first_submitted_qc>
  <results_first_posted type="Estimate">May 11, 2016</results_first_posted>
  <last_update_submitted>July 23, 2018</last_update_submitted>
  <last_update_submitted_qc>July 23, 2018</last_update_submitted_qc>
  <last_update_posted type="Actual">August 21, 2018</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Diabetes Mellitus</mesh_term>
    <mesh_term>Diabetes Mellitus, Type 2</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Metformin</mesh_term>
    <mesh_term>Sitagliptin Phosphate</mesh_term>
    <mesh_term>Glimepiride</mesh_term>
    <mesh_term>Acarbose</mesh_term>
    <mesh_term>Repaglinide</mesh_term>
    <mesh_term>Gliclazide</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>https://www.merck.com/clinical-trials/pdf/ProcedureAccessClinicalTrialData.pdf</ipd_description>
    <ipd_url>http://engagezone.msd.com/ds_documentation.php</ipd_url>
  </patient_data>

  <clinical_results>

    <participant_flow>
      <recruitment_details>Adult Chinese participants (≥18 and ≤75 years of age) with a diagnosis of Type 2 Diabetes Mellitus (T2DM) and inadequate glycemic control were selected to participate in this study.</recruitment_details>
      <pre_assignment_details>There were 2344 participants who achieved A1C&lt;7% in Phase 1; they completed Phase 1 and did not enter Phase 2. Of the remaining 2589 participants, 377 participants did not meet randomization criteria to enter Phase 2.</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>Phase 1: Sitagliptin + Metformin</title>
          <description>During Phase 1, participants received sitagliptin 100 mg + metformin (Week 0 through Week 20). There were 5570 participants enrolled in Phase 1.</description>
        </group>
        <group group_id="P2">
          <title>Phase 2: Metformin + Sitagliptin + Glimepiride</title>
          <description>During Phase 2, participants received up to 6 mg glimepiride daily as an add-on to metformin + sitagliptin combination therapy for 24 weeks (Week 20 through Week 44). There were 552 participants randomized to this arm in Phase 2.</description>
        </group>
        <group group_id="P3">
          <title>Phase 2: Metformin + Sitagliptin + Repaglinide</title>
          <description>During Phase 2, participants received up to 16 mg repaglinide daily as an add-on to metformin + sitagliptin combination therapy for 24 weeks (Week 20 through Week 44). There were 550 participants randomized to this arm in Phase 2.</description>
        </group>
        <group group_id="P4">
          <title>Phase 2: Metformin + Sitagliptin + Acarbose</title>
          <description>During Phase 2, participants received 50-100 mg acarbose three times daily as an add-on to metformin + sitagliptin combination therapy for 24 weeks (Week 20 through Week 44). There were 556 participants randomized to this arm in Phase 2.</description>
        </group>
        <group group_id="P5">
          <title>Phase 2: Metformin + Sitagliptin + Gliclazide</title>
          <description>During Phase 2, participants received 30-120 mg gliclazide daily as an add-on to metformin + sitagliptin combinatino therapy for 24 weeks (Week 20 through Week 44). There were 554 participants randomized to this arm in Phase 2.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Phase 1</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="5570"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="0"/>
                <participants group_id="P5" count="0"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="4933"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="0"/>
                <participants group_id="P5" count="0"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="637"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="0"/>
                <participants group_id="P5" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Clinical Adverse Event</title>
              <participants_list>
                <participants group_id="P1" count="80"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="0"/>
                <participants group_id="P5" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Death</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="0"/>
                <participants group_id="P5" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Hyperglycemia (lack of efficacy)</title>
              <participants_list>
                <participants group_id="P1" count="13"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="0"/>
                <participants group_id="P5" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Laboratory Adverse Event</title>
              <participants_list>
                <participants group_id="P1" count="16"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="0"/>
                <participants group_id="P5" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Lost to Follow-up</title>
              <participants_list>
                <participants group_id="P1" count="147"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="0"/>
                <participants group_id="P5" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Travel, moving, etc.</title>
              <participants_list>
                <participants group_id="P1" count="30"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="0"/>
                <participants group_id="P5" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Physician Decision</title>
              <participants_list>
                <participants group_id="P1" count="13"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="0"/>
                <participants group_id="P5" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Protocol Violation</title>
              <participants_list>
                <participants group_id="P1" count="118"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="0"/>
                <participants group_id="P5" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="218"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="0"/>
                <participants group_id="P5" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
        <period>
          <title>Phase 2</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="552"/>
                <participants group_id="P3" count="550"/>
                <participants group_id="P4" count="556"/>
                <participants group_id="P5" count="554"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="500"/>
                <participants group_id="P3" count="505"/>
                <participants group_id="P4" count="508"/>
                <participants group_id="P5" count="507"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="52"/>
                <participants group_id="P3" count="45"/>
                <participants group_id="P4" count="48"/>
                <participants group_id="P5" count="47"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Clinical Adverse Event</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="10"/>
                <participants group_id="P3" count="10"/>
                <participants group_id="P4" count="6"/>
                <participants group_id="P5" count="11"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Death</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="1"/>
                <participants group_id="P4" count="0"/>
                <participants group_id="P5" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Hyperglycemia (lack of efficacy)</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="0"/>
                <participants group_id="P5" count="2"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Laboratory Adverse Event</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="1"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="1"/>
                <participants group_id="P5" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Lost to Follow-up</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="10"/>
                <participants group_id="P3" count="6"/>
                <participants group_id="P4" count="9"/>
                <participants group_id="P5" count="5"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Travel, moving, etc.</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="2"/>
                <participants group_id="P3" count="3"/>
                <participants group_id="P4" count="3"/>
                <participants group_id="P5" count="5"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Physician Decision</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="2"/>
                <participants group_id="P3" count="0"/>
                <participants group_id="P4" count="1"/>
                <participants group_id="P5" count="2"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Protocol Violation</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="19"/>
                <participants group_id="P3" count="19"/>
                <participants group_id="P4" count="13"/>
                <participants group_id="P5" count="9"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="8"/>
                <participants group_id="P3" count="6"/>
                <participants group_id="P4" count="15"/>
                <participants group_id="P5" count="12"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>This population includes all participants who enrolled in Phase 1 and were GCP compliant.</population>
      <group_list>
        <group group_id="B1">
          <title>Overall Study</title>
          <description>During Phase 1, participants received sitagliptin 100 mg + metformin (Week 0 through Week 20).</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="5535"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>Years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="53.1" spread="9.9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2240"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="3295"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Change From Phase 2 Baseline to Week 44 in Hemoglobin A1c (HbA1c) Levels (Phase 2)</title>
        <description>HbA1c is blood marker used to report average blood glucose levels over prolonged periods of time and is reported as a percentage (%). Change from baseline reflects the Week 44 A1C minus baseline A1C. Baseline is defined as Visit 6/Week 20. If this measurement was unavailable, the Week 16 value was used. Change from baseline was based on the constrained longitudinal data analysis (cLDA) model including all available measurements from baseline through the last visit. The terms in the cLDA model include treatment, time in weeks (categorical), regions, and treatment-by-time interaction.</description>
        <time_frame>Phase 2 Baseline (Week 20) and Week 44</time_frame>
        <population>Per-Protocol (PP) population - excluded those participants who were identified as protocol violators and those who were non-compliant with Good Clinical Practice (GCP) requirements.</population>
        <group_list>
          <group group_id="O1">
            <title>Phase 2: Metformin + Sitagliptin + Glimepiride</title>
            <description>During Phase 2, participants received up to 6 mg glimepiride daily as an add-on to metformin + sitagliptin combination therapy for 24 weeks (Week 20 through Week 44).</description>
          </group>
          <group group_id="O2">
            <title>Phase 2: Metformin + Sitagliptin + Repaglinide</title>
            <description>During Phase 2, participants received up to 16 mg repaglinide daily as an add-on to metfomin + sitagliptin combination therapy for 24 weeks (Week 20 through Week 44).</description>
          </group>
          <group group_id="O3">
            <title>Phase 2: Metformin + Sitagliptin + Acarbose</title>
            <description>During Phase 2, participants received 50-100 mg acarbose three times daily as an add-on to metformin + sitagliptin combination therapy for 24 weeks (Week 20 through Week 44).</description>
          </group>
          <group group_id="O4">
            <title>Phase 2: Metformin + Sitagliptin + Gliclazide</title>
            <description>During Phase 2, participants received 30-120 mg gliclazide daily as an add-on to metformin + sitagliptin combination therapy for 24 weeks (Week 20 through Week 44).</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Phase 2 Baseline to Week 44 in Hemoglobin A1c (HbA1c) Levels (Phase 2)</title>
          <description>HbA1c is blood marker used to report average blood glucose levels over prolonged periods of time and is reported as a percentage (%). Change from baseline reflects the Week 44 A1C minus baseline A1C. Baseline is defined as Visit 6/Week 20. If this measurement was unavailable, the Week 16 value was used. Change from baseline was based on the constrained longitudinal data analysis (cLDA) model including all available measurements from baseline through the last visit. The terms in the cLDA model include treatment, time in weeks (categorical), regions, and treatment-by-time interaction.</description>
          <population>Per-Protocol (PP) population - excluded those participants who were identified as protocol violators and those who were non-compliant with Good Clinical Practice (GCP) requirements.</population>
          <units>Percent</units>
          <param>Least Squares Mean</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="414"/>
                <count group_id="O2" value="418"/>
                <count group_id="O3" value="472"/>
                <count group_id="O4" value="418"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.65" spread="0.84" lower_limit="-0.73" upper_limit="-0.57"/>
                    <measurement group_id="O2" value="-0.62" spread="0.84" lower_limit="-0.69" upper_limit="-0.54"/>
                    <measurement group_id="O3" value="-0.46" spread="0.83" lower_limit="-0.53" upper_limit="-0.38"/>
                    <measurement group_id="O4" value="-0.69" spread="0.90" lower_limit="-0.77" upper_limit="-0.61"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O3</group_id>
            </group_id_list>
            <groups_desc>Pairwise Comparison</groups_desc>
            <non_inferiority_type>Non-Inferiority or Equivalence</non_inferiority_type>
            <non_inferiority_desc>Non-inferiority criterion are met when the upper limit of the two-sided 98.34% CI for the difference in LS means is less than or equal to the pre-specified non-inferiority margin of 0.3%.</non_inferiority_desc>
            <param_type>Difference in LS Means</param_type>
            <param_value>0.19</param_value>
            <ci_percent>98.34</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>0.02</ci_lower_limit>
            <ci_upper_limit>0.36</ci_upper_limit>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Pairwise Comparison</groups_desc>
            <non_inferiority_type>Non-Inferiority or Equivalence</non_inferiority_type>
            <non_inferiority_desc>Non-inferiority criterion are met when the upper limit of the two-sided 98.34% CI for the difference in LS means is less than or equal to the pre-specified non-inferiority margin of 0.3%.</non_inferiority_desc>
            <param_type>Difference in LS Means</param_type>
            <param_value>0.03</param_value>
            <ci_percent>98.34</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-0.15</ci_lower_limit>
            <ci_upper_limit>0.21</ci_upper_limit>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <groups_desc>Pairwise Comparison</groups_desc>
            <non_inferiority_type>Non-Inferiority or Equivalence</non_inferiority_type>
            <non_inferiority_desc>Non-inferiority criterion are met when the upper limit of the two-sided 98.34% CI for the difference in LS means is less than or equal to the pre-specified non-inferiority margin of 0.3%.</non_inferiority_desc>
            <param_type>Difference in LS Means</param_type>
            <param_value>-0.05</param_value>
            <ci_percent>98.34</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-0.23</ci_lower_limit>
            <ci_upper_limit>0.14</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change From Phase 2 Baseline to Week 44 in Participant Body Weight (Phase 2)</title>
        <description>Change from baseline in body weight in Phase 2 was reported. Change from baseline reflects the Week 44 body weight minus baseline body weight. Baseline is defined as Visit 6/Week 20. If this measurement was unavailable, the Week 16 value was used.</description>
        <time_frame>Phase 2 Baseline (Week 20), Week 44</time_frame>
        <population>All Participants as Treated (APaT) - all randomized participants who received at least one (1) dose of study treatment and were compliant with GCP requirements.</population>
        <group_list>
          <group group_id="O1">
            <title>Phase 2: Metformin + Sitagliptin + Glimepiride</title>
            <description>During Phase 2, participants received up to 6 mg glimepiride daily as an add-on to metformin + sitagliptin combination therapy for 24 weeks (Week 20 through Week 44). There were 501 participants that contributed to the week 44 analysis.</description>
          </group>
          <group group_id="O2">
            <title>Phase 2: Metformin + Sitagliptin + Repaglinide</title>
            <description>During Phase 2, participants received up to 16 mg repaglinide daily as an add-on to metfomin + sitagliptin combination therapy for 24 weeks (Week 20 through Week 44). There were 502 participants that contributed to the week 44 analysis.</description>
          </group>
          <group group_id="O3">
            <title>Phase 2: Metformin + Sitagliptin + Acarbose</title>
            <description>During Phase 2, participants received 50-100 mg acarbose three times daily as an add-on to metformin + sitagliptin combination therapy for 24 weeks (Week 20 through Week 44). There were 551 participants that contributed to the week 44 analysis.</description>
          </group>
          <group group_id="O4">
            <title>Phase 2: Metformin + Sitagliptin + Gliclazide</title>
            <description>During Phase 2, participants received 30-120 mg gliclazide daily as an add-on to metformin + sitagliptin combination therapy for 24 weeks (Week 20 through Week 44). There were 550 participants that contributed to the week 44 analysis.</description>
          </group>
        </group_list>
        <measure>
          <title>Change From Phase 2 Baseline to Week 44 in Participant Body Weight (Phase 2)</title>
          <description>Change from baseline in body weight in Phase 2 was reported. Change from baseline reflects the Week 44 body weight minus baseline body weight. Baseline is defined as Visit 6/Week 20. If this measurement was unavailable, the Week 16 value was used.</description>
          <population>All Participants as Treated (APaT) - all randomized participants who received at least one (1) dose of study treatment and were compliant with GCP requirements.</population>
          <units>kg</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="501"/>
                <count group_id="O2" value="502"/>
                <count group_id="O3" value="509"/>
                <count group_id="O4" value="506"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.4" spread="2.6"/>
                    <measurement group_id="O2" value="0.2" spread="2.5"/>
                    <measurement group_id="O3" value="-0.9" spread="2.5"/>
                    <measurement group_id="O4" value="0.2" spread="2.4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percentage of Participants With Hypoglycemia Events (Phase 2)</title>
        <description>Hypoglycemia events represent epidsodes symptomatic of hypoglycemia (e.g., weakness, dizziness, shakiness, increased sweating, palpitations, or confusion) and/or finger stick glucose values of ≤70 mg/dL (3.9 mmol/L). The percentage of participants with hypoglycemia events was reported.</description>
        <time_frame>From Week 20 through Week 44</time_frame>
        <population>All Participants as Treated (APaT) - all randomized participants who received at least one (1) dose of study treatment and were compliant with GCP requirements.</population>
        <group_list>
          <group group_id="O1">
            <title>Phase 2: Metformin + Sitagliptin + Glimepiride</title>
            <description>During Phase 2, participants received up to 6 mg glimepiride daily as an add-on to metformin + sitagliptin combination therapy for 24 weeks (Week 20 through Week 44).</description>
          </group>
          <group group_id="O2">
            <title>Phase 2: Metformin + Sitagliptin + Repaglinide</title>
            <description>During Phase 2, participants received up to 16 mg repaglinide daily as an add-on to metfomin + sitagliptin combination therapy for 24 weeks (Week 20 through Week 44).</description>
          </group>
          <group group_id="O3">
            <title>Phase 2: Metformin + Sitagliptin + Acarbose</title>
            <description>During Phase 2, participants received 50-100 mg acarbose three times daily as an add-on to metformin + sitagliptin combination therapy for 24 weeks (Week 20 through Week 44).</description>
          </group>
          <group group_id="O4">
            <title>Phase 2: Metformin + Sitagliptin + Gliclazide</title>
            <description>During Phase 2, participants received 30-120 mg gliclazide daily as an add-on to metformin + sitagliptin combination therapy for 24 weeks (Week 20 through Week 44).</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Participants With Hypoglycemia Events (Phase 2)</title>
          <description>Hypoglycemia events represent epidsodes symptomatic of hypoglycemia (e.g., weakness, dizziness, shakiness, increased sweating, palpitations, or confusion) and/or finger stick glucose values of ≤70 mg/dL (3.9 mmol/L). The percentage of participants with hypoglycemia events was reported.</description>
          <population>All Participants as Treated (APaT) - all randomized participants who received at least one (1) dose of study treatment and were compliant with GCP requirements.</population>
          <units>Percentage of Participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="549"/>
                <count group_id="O2" value="545"/>
                <count group_id="O3" value="551"/>
                <count group_id="O4" value="550"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="8.9"/>
                    <measurement group_id="O2" value="6.1"/>
                    <measurement group_id="O3" value="0.5"/>
                    <measurement group_id="O4" value="3.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O3</group_id>
            </group_id_list>
            <groups_desc>Difference in % vs. Glimepiride</groups_desc>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>&lt;0.001</p_value>
            <method>Miettinen &amp; Nurminen</method>
            <param_type>Estimate</param_type>
            <param_value>-8.4</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-11.1</ci_lower_limit>
            <ci_upper_limit>-6.1</ci_upper_limit>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Difference in % vs. Glimepiride</groups_desc>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>0.072</p_value>
            <method>Miettinen &amp; Nurminen</method>
            <param_type>Estimate</param_type>
            <param_value>-2.9</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-6.1</ci_lower_limit>
            <ci_upper_limit>0.3</ci_upper_limit>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <groups_desc>Difference in % vs. Glimepiride</groups_desc>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>&lt;0.001</p_value>
            <method>Miettinen &amp; Nurminen</method>
            <param_type>Estimate</param_type>
            <param_value>-5.3</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-8.3</ci_lower_limit>
            <ci_upper_limit>-2.5</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percentage of Participants With a Gastrointestinal (GI) AE of Nausea (Phase 2)</title>
        <description>The percentage of participants with a GI AE of &quot;nausea&quot; was reported.</description>
        <time_frame>From Week 20 through Week 44</time_frame>
        <population>All Participants as Treated (APaT) - all randomized participants who received at least one (1) dose of study treatment and were compliant with GCP requirements.</population>
        <group_list>
          <group group_id="O1">
            <title>Phase 2: Metformin + Sitagliptin + Glimepiride</title>
            <description>During Phase 2, participants received up to 6 mg glimepiride daily as an add-on to metformin + sitagliptin combination therapy for 24 weeks (Week 20 through Week 44).</description>
          </group>
          <group group_id="O2">
            <title>Phase 2: Metformin + Sitagliptin + Repaglinide</title>
            <description>During Phase 2, participants received up to 16 mg repaglinide daily as an add-on to metfomin + sitagliptin combination therapy for 24 weeks (Week 20 through Week 44).</description>
          </group>
          <group group_id="O3">
            <title>Phase 2: Metformin + Sitagliptin + Acarbose</title>
            <description>During Phase 2, participants received 50-100 mg acarbose three times daily as an add-on to metformin + sitagliptin combination therapy for 24 weeks (Week 20 through Week 44).</description>
          </group>
          <group group_id="O4">
            <title>Phase 2: Metformin + Sitagliptin + Gliclazide</title>
            <description>During Phase 2, participants received 30-120 mg gliclazide daily as an add-on to metformin + sitagliptin combination therapy for 24 weeks (Week 20 through Week 44).</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Participants With a Gastrointestinal (GI) AE of Nausea (Phase 2)</title>
          <description>The percentage of participants with a GI AE of &quot;nausea&quot; was reported.</description>
          <population>All Participants as Treated (APaT) - all randomized participants who received at least one (1) dose of study treatment and were compliant with GCP requirements.</population>
          <units>Percentage of Participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="549"/>
                <count group_id="O2" value="545"/>
                <count group_id="O3" value="551"/>
                <count group_id="O4" value="550"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="0.4"/>
                    <measurement group_id="O4" value="0.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O3</group_id>
            </group_id_list>
            <groups_desc>Difference in % vs. Glimepiride</groups_desc>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>0.158</p_value>
            <method>Miettinen &amp; Nurminen</method>
            <param_type>Estimate</param_type>
            <param_value>0.4</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-0.3</ci_lower_limit>
            <ci_upper_limit>1.3</ci_upper_limit>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Difference in % vs. Glimepiride</groups_desc>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>&gt;0.999</p_value>
            <method>Miettinen &amp; Nurminen</method>
            <param_type>Estimate</param_type>
            <param_value>0.0</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-0.7</ci_lower_limit>
            <ci_upper_limit>0.7</ci_upper_limit>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <groups_desc>Difference in % vs. Glimepiride</groups_desc>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>0.318</p_value>
            <method>Miettinen &amp; Nurminen</method>
            <param_type>Estimate</param_type>
            <param_value>0.2</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-0.5</ci_lower_limit>
            <ci_upper_limit>1.0</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percentage of Participants With a GI AE of Vomiting (Phase 2)</title>
        <description>The percentage of participants with a GI AE of &quot;vomiting&quot; was reported.</description>
        <time_frame>From Week 20 through Week 44</time_frame>
        <population>All Participants as Treated (APaT) - all randomized participants who received at least one (1) dose of study treatment and were compliant with GCP requirements.</population>
        <group_list>
          <group group_id="O1">
            <title>Phase 2: Metformin + Sitagliptin + Glimepiride</title>
            <description>During Phase 2, participants received up to 6 mg glimepiride daily as an add-on to metformin + sitagliptin combination therapy for 24 weeks (Week 20 through Week 44).</description>
          </group>
          <group group_id="O2">
            <title>Phase 2: Metformin + Sitagliptin + Repaglinide</title>
            <description>During Phase 2, participants received up to 16 mg repaglinide daily as an add-on to metfomin + sitagliptin combination therapy for 24 weeks (Week 20 through Week 44).</description>
          </group>
          <group group_id="O3">
            <title>Phase 2: Metformin + Sitagliptin + Acarbose</title>
            <description>During Phase 2, participants received 50-100 mg acarbose three times daily as an add-on to metformin + sitagliptin combination therapy for 24 weeks (Week 20 through Week 44).</description>
          </group>
          <group group_id="O4">
            <title>Phase 2: Metformin + Sitagliptin + Gliclazide</title>
            <description>During Phase 2, participants received 30-120 mg gliclazide daily as an add-on to metformin + sitagliptin combination therapy for 24 weeks (Week 20 through Week 44).</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Participants With a GI AE of Vomiting (Phase 2)</title>
          <description>The percentage of participants with a GI AE of &quot;vomiting&quot; was reported.</description>
          <population>All Participants as Treated (APaT) - all randomized participants who received at least one (1) dose of study treatment and were compliant with GCP requirements.</population>
          <units>Percentage of Participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="549"/>
                <count group_id="O2" value="545"/>
                <count group_id="O3" value="551"/>
                <count group_id="O4" value="550"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.2"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="0.2"/>
                    <measurement group_id="O4" value="0.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O3</group_id>
            </group_id_list>
            <groups_desc>Difference in % vs. Glimepiride</groups_desc>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>0.998</p_value>
            <method>Miettinen &amp; Nurminen</method>
            <param_type>Estimate</param_type>
            <param_value>-0.0</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-0.9</ci_lower_limit>
            <ci_upper_limit>0.9</ci_upper_limit>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Difference in % vs. Glimepiride</groups_desc>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>0.319</p_value>
            <method>Miettinen &amp; Nurminen</method>
            <param_type>Estimate</param_type>
            <param_value>-0.2</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-1.0</ci_lower_limit>
            <ci_upper_limit>0.5</ci_upper_limit>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <groups_desc>Difference in % vs. Glimepiride</groups_desc>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>0.999</p_value>
            <method>Miettinen &amp; Nurminen</method>
            <param_type>Estimate</param_type>
            <param_value>-0.0</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-0.9</ci_lower_limit>
            <ci_upper_limit>0.9</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percentage of Participants With a GI AE of Diarrhea (Phase 2)</title>
        <description>The percentage of participants with a GI AE of &quot;diarrhea&quot; was reported.</description>
        <time_frame>From Week 20 through Week 44</time_frame>
        <population>All Participants as Treated (APaT) - all randomized participants who received at least one (1) dose of study treatment and were compliant with GCP requirements.</population>
        <group_list>
          <group group_id="O1">
            <title>Phase 2: Metformin + Sitagliptin + Glimepiride</title>
            <description>During Phase 2, participants received up to 6 mg glimepiride daily as an add-on to metformin + sitagliptin combination therapy for 24 weeks (Week 20 through Week 44).</description>
          </group>
          <group group_id="O2">
            <title>Phase 2: Metformin + Sitagliptin + Repaglinide</title>
            <description>During Phase 2, participants received up to 16 mg repaglinide daily as an add-on to metfomin + sitagliptin combination therapy for 24 weeks (Week 20 through Week 44).</description>
          </group>
          <group group_id="O3">
            <title>Phase 2: Metformin + Sitagliptin + Acarbose</title>
            <description>During Phase 2, participants received 50-100 mg acarbose three times daily as an add-on to metformin + sitagliptin combination therapy for 24 weeks (Week 20 through Week 44).</description>
          </group>
          <group group_id="O4">
            <title>Phase 2: Metformin + Sitagliptin + Gliclazide</title>
            <description>During Phase 2, participants received 30-120 mg gliclazide daily as an add-on to metformin + sitagliptin combination therapy for 24 weeks (Week 20 through Week 44).</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Participants With a GI AE of Diarrhea (Phase 2)</title>
          <description>The percentage of participants with a GI AE of &quot;diarrhea&quot; was reported.</description>
          <population>All Participants as Treated (APaT) - all randomized participants who received at least one (1) dose of study treatment and were compliant with GCP requirements.</population>
          <units>Percentage of Participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="549"/>
                <count group_id="O2" value="545"/>
                <count group_id="O3" value="551"/>
                <count group_id="O4" value="550"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.5"/>
                    <measurement group_id="O2" value="0.4"/>
                    <measurement group_id="O3" value="0.4"/>
                    <measurement group_id="O4" value="0.9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O3</group_id>
            </group_id_list>
            <groups_desc>Difference in % vs. Glimepiride</groups_desc>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>0.651</p_value>
            <method>Miettinen &amp; Nurminen</method>
            <param_type>Estimate</param_type>
            <param_value>-0.2</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-1.3</ci_lower_limit>
            <ci_upper_limit>0.8</ci_upper_limit>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Difference in % vs. Glimepiride</groups_desc>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>0.660</p_value>
            <method>Miettinen &amp; Nurminen</method>
            <param_type>Estimate</param_type>
            <param_value>-0.2</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-1.3</ci_lower_limit>
            <ci_upper_limit>0.8</ci_upper_limit>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <groups_desc>Difference in % vs. Glimepiride</groups_desc>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>0.480</p_value>
            <method>Miettinen &amp; Nurminen</method>
            <param_type>Estimate</param_type>
            <param_value>0.4</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-0.8</ci_lower_limit>
            <ci_upper_limit>1.6</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Percentage of Participants With a GI AE of Abdominal Pain (Phase 2)</title>
        <description>The percentage of participants with a GI AE of &quot;abdominal pain&quot; was reported.</description>
        <time_frame>From Week 20 through Week 44</time_frame>
        <population>All Participants as Treated (APaT) - all randomized participants who received at least one (1) dose of study treatment and were compliant with GCP requirements.</population>
        <group_list>
          <group group_id="O1">
            <title>Phase 2: Metformin + Sitagliptin + Glimepiride</title>
            <description>During Phase 2, participants received up to 6 mg glimepiride daily as an add-on to metformin + sitagliptin combination therapy for 24 weeks (Week 20 through Week 44).</description>
          </group>
          <group group_id="O2">
            <title>Phase 2: Metformin + Sitagliptin + Repaglinide</title>
            <description>During Phase 2, participants received up to 16 mg repaglinide daily as an add-on to metfomin + sitagliptin combination therapy for 24 weeks (Week 20 through Week 44).</description>
          </group>
          <group group_id="O3">
            <title>Phase 2: Metformin + Sitagliptin + Acarbose</title>
            <description>During Phase 2, participants received 50-100 mg acarbose three times daily as an add-on to metformin + sitagliptin combination therapy for 24 weeks (Week 20 through Week 44).</description>
          </group>
          <group group_id="O4">
            <title>Phase 2: Metformin + Sitagliptin + Gliclazide</title>
            <description>During Phase 2, participants received 30-120 mg gliclazide daily as an add-on to metformin + sitagliptin combination therapy for 24 weeks (Week 20 through Week 44).</description>
          </group>
        </group_list>
        <measure>
          <title>Percentage of Participants With a GI AE of Abdominal Pain (Phase 2)</title>
          <description>The percentage of participants with a GI AE of &quot;abdominal pain&quot; was reported.</description>
          <population>All Participants as Treated (APaT) - all randomized participants who received at least one (1) dose of study treatment and were compliant with GCP requirements.</population>
          <units>Percentage of Participants</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="549"/>
                <count group_id="O2" value="545"/>
                <count group_id="O3" value="551"/>
                <count group_id="O4" value="550"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="0.4"/>
                    <measurement group_id="O4" value="0.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O3</group_id>
            </group_id_list>
            <groups_desc>Difference in % vs. Glimepiride</groups_desc>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>0.158</p_value>
            <method>Miettinen &amp; Nurminen</method>
            <param_type>Estimate</param_type>
            <param_value>0.4</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-0.3</ci_lower_limit>
            <ci_upper_limit>1.3</ci_upper_limit>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <groups_desc>Difference in % vs. Glimepiride</groups_desc>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>&gt;0.999</p_value>
            <method>Miettinen &amp; Nurminen</method>
            <param_type>Estimate</param_type>
            <param_value>0.0</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-0.7</ci_lower_limit>
            <ci_upper_limit>0.7</ci_upper_limit>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O4</group_id>
            </group_id_list>
            <groups_desc>Difference in % vs. Glimepiride</groups_desc>
            <non_inferiority_type>Superiority or Other</non_inferiority_type>
            <p_value>0.318</p_value>
            <method>Miettinen &amp; Nurminen</method>
            <param_type>Estimate</param_type>
            <param_value>0.2</param_value>
            <ci_percent>95</ci_percent>
            <ci_n_sides>2-Sided</ci_n_sides>
            <ci_lower_limit>-0.5</ci_lower_limit>
            <ci_upper_limit>1.0</ci_upper_limit>
          </analysis>
        </analysis_list>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Up to 46 Weeks</time_frame>
      <desc>All Participants as Treated (APaT) - all participants enrolled (Phase 1) or randomized (Phase 2) who received at least one dose of study treatment and complied with GCP requirements. Participants were included in the treatment group corresponding to the study treatment they actually received.</desc>
      <group_list>
        <group group_id="E1">
          <title>Phase 1: Sitagliptin + Metformin</title>
          <description>During Phase 1, participants received sitagliptin 100 mg + metformin for 20 weeks (Week 0 through Week 20).</description>
        </group>
        <group group_id="E2">
          <title>Phase 2: Metformin + Sitagliptin + Acarbose</title>
          <description>During Phase 2, participants received 50-100 mg acarbose three times daily as an add-on to metformin + sitagliptin combination therapy for 24 weeks (Week 20 through Week 44).</description>
        </group>
        <group group_id="E3">
          <title>Phase 2: Metformin + Sitagliptin + Repaglinide</title>
          <description>During Phase 2, participants received up to 16 mg repaglinide daily as an add-on to metformin + sitagliptin combination therapy for 24 weeks (Week 20 through Week 44).</description>
        </group>
        <group group_id="E4">
          <title>Phase 2: Metformin + Sitagliptin + Gliclazide</title>
          <description>During Phase 2, participants received 30-120 mg gliclazide daily as an add-on to metformin + sitagliptin combination therapy for 24 weeks (Week 20 through Week 44).</description>
        </group>
        <group group_id="E5">
          <title>Phase 2: Metformin + Sitagliptin + Glimepiride</title>
          <description>During Phase 2, participants received up to 6 mg glimepiride daily as an add-on to metformin + sitagliptin combination therapy for 24 weeks (Week 20 through Week 44).</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>MedDRA 18.0</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="63" subjects_at_risk="5527"/>
                <counts group_id="E2" subjects_affected="11" subjects_at_risk="551"/>
                <counts group_id="E3" subjects_affected="9" subjects_at_risk="545"/>
                <counts group_id="E4" subjects_affected="10" subjects_at_risk="550"/>
                <counts group_id="E5" subjects_affected="8" subjects_at_risk="549"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Angina Pectoris</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="5527"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="551"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="545"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="550"/>
                <counts group_id="E5" events="1" subjects_affected="1" subjects_at_risk="549"/>
              </event>
              <event>
                <sub_title>Angina Unstable</sub_title>
                <counts group_id="E1" events="5" subjects_affected="5" subjects_at_risk="5527"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="551"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="545"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="550"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="549"/>
              </event>
              <event>
                <sub_title>Arteriosclerosis Coronary Artery</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="5527"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="551"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="545"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="550"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="549"/>
              </event>
              <event>
                <sub_title>Coronary Artery Disease</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="5527"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="551"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="545"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="550"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="549"/>
              </event>
              <event>
                <sub_title>Acute Myocardial Infarction</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="5527"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="551"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="545"/>
                <counts group_id="E4" events="2" subjects_affected="2" subjects_at_risk="550"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="549"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Eye disorders</title>
            <event_list>
              <event>
                <sub_title>Cataract</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="5527"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="551"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="545"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="550"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="549"/>
              </event>
              <event>
                <sub_title>Diabetic Retinopathy</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="5527"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="551"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="545"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="550"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="549"/>
              </event>
              <event>
                <sub_title>Entropion</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="5527"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="551"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="545"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="550"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="549"/>
              </event>
              <event>
                <sub_title>Optic Ischaemic Neuropathy</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="5527"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="551"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="545"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="550"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="549"/>
              </event>
              <event>
                <sub_title>Pterygium</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="5527"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="551"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="545"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="550"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="549"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Gastric Polyps</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="5527"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="551"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="545"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="550"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="549"/>
              </event>
              <event>
                <sub_title>Gastrointestinal Perforation</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="5527"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="551"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="545"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="550"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="549"/>
              </event>
              <event>
                <sub_title>Large Intestine Polyp</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="5527"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="551"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="545"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="550"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="549"/>
              </event>
              <event>
                <sub_title>Duodenal Ulcer Haemorrhage</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="5527"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="551"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="545"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="550"/>
                <counts group_id="E5" events="1" subjects_affected="1" subjects_at_risk="549"/>
              </event>
              <event>
                <sub_title>Intestinal Obstruction</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="5527"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="551"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="545"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="550"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="549"/>
              </event>
              <event>
                <sub_title>Pancreatitis Acute</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="5527"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="551"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="545"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="550"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="549"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Sudden Death</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="5527"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="551"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="545"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="550"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="549"/>
              </event>
              <event>
                <sub_title>Vascular Stent Occlusion</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="5527"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="551"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="545"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="550"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="549"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Hepatobiliary disorders</title>
            <event_list>
              <event>
                <sub_title>Cholelithiasis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="5527"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="551"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="545"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="550"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="549"/>
              </event>
              <event>
                <sub_title>Diabetic Hepatopathy</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="5527"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="551"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="545"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="550"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="549"/>
              </event>
              <event>
                <sub_title>Hepatic Function Abnormal</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="5527"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="551"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="545"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="550"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="549"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Anal Abscess</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="5527"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="551"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="545"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="550"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="549"/>
              </event>
              <event>
                <sub_title>Appendicitis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="5527"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="551"/>
                <counts group_id="E3" events="2" subjects_affected="2" subjects_at_risk="545"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="550"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="549"/>
              </event>
              <event>
                <sub_title>Epididymitis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="5527"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="551"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="545"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="550"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="549"/>
              </event>
              <event>
                <sub_title>Otitis Media</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="5527"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="551"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="545"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="550"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="549"/>
              </event>
              <event>
                <sub_title>Pneumonia</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="5527"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="551"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="545"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="550"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="549"/>
              </event>
              <event>
                <sub_title>Pulmonary Tuberculosis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="5527"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="551"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="545"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="550"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="549"/>
              </event>
              <event>
                <sub_title>Spermatic Cord Funiculitis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="5527"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="551"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="545"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="550"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="549"/>
              </event>
              <event>
                <sub_title>Vestibular Neuronitis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="5527"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="551"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="545"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="550"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="549"/>
              </event>
              <event>
                <sub_title>Bronchitis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="5527"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="551"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="545"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="550"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="549"/>
              </event>
              <event>
                <sub_title>Liver Abscess</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="5527"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="551"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="545"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="550"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="549"/>
              </event>
              <event>
                <sub_title>Parotitis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="5527"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="551"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="545"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="550"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="549"/>
              </event>
              <event>
                <sub_title>Urinary Tract Infection</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="5527"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="551"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="545"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="550"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="549"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Abdominal Injury</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="5527"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="551"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="545"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="550"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="549"/>
              </event>
              <event>
                <sub_title>Fracture</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="5527"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="551"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="545"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="550"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="549"/>
              </event>
              <event>
                <sub_title>Lumbar Vertebral Fracture</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="5527"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="551"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="545"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="550"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="549"/>
              </event>
              <event>
                <sub_title>Meniscus Injury</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="5527"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="551"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="545"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="550"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="549"/>
              </event>
              <event>
                <sub_title>Road Traffic Accident</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="5527"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="551"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="545"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="550"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="549"/>
              </event>
              <event>
                <sub_title>Spinal Compression Fracture</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="5527"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="551"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="545"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="550"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="549"/>
              </event>
              <event>
                <sub_title>Fall</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="5527"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="551"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="545"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="550"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="549"/>
              </event>
              <event>
                <sub_title>Hand Fracture</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="5527"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="551"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="545"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="550"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="549"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Diabetes Mellitus Inadequate Control</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="5527"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="551"/>
                <counts group_id="E3" events="3" subjects_affected="3" subjects_at_risk="545"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="550"/>
                <counts group_id="E5" events="1" subjects_affected="1" subjects_at_risk="549"/>
              </event>
              <event>
                <sub_title>Diabetic Ketoacidosis</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="5527"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="551"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="545"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="550"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="549"/>
              </event>
              <event>
                <sub_title>Gout</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="5527"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="551"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="545"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="550"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="549"/>
              </event>
              <event>
                <sub_title>Hypoglycaemia</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="5527"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="551"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="545"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="550"/>
                <counts group_id="E5" events="1" subjects_affected="1" subjects_at_risk="549"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Gouty Arthritis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="5527"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="551"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="545"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="550"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="549"/>
              </event>
              <event>
                <sub_title>Osteoarthritis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="5527"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="551"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="545"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="550"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="549"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Neoplasms benign, malignant and unspecified (incl cysts and polyps)</title>
            <event_list>
              <event>
                <sub_title>Brain Neoplasm</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="5527"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="551"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="545"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="550"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="549"/>
              </event>
              <event>
                <sub_title>Gallbladder Cancer</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="5527"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="551"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="545"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="550"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="549"/>
              </event>
              <event>
                <sub_title>Gastric Cancer</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="5527"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="551"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="545"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="550"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="549"/>
              </event>
              <event>
                <sub_title>Lipoma</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="5527"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="551"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="545"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="550"/>
                <counts group_id="E5" events="1" subjects_affected="1" subjects_at_risk="549"/>
              </event>
              <event>
                <sub_title>Ovarian Adenoma</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="5527"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="551"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="545"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="550"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="549"/>
              </event>
              <event>
                <sub_title>Pancreatic Carcinoma</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="5527"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="551"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="545"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="550"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="549"/>
              </event>
              <event>
                <sub_title>Rectal Cancer</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="5527"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="551"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="545"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="550"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="549"/>
              </event>
              <event>
                <sub_title>Thyroid Neoplasm</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="5527"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="551"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="545"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="550"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="549"/>
              </event>
              <event>
                <sub_title>Myelodysplastic Syndrome</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="5527"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="551"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="545"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="550"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="549"/>
              </event>
              <event>
                <sub_title>Tongue Neoplasm Malignant Stage Unspecified</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="5527"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="551"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="545"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="550"/>
                <counts group_id="E5" events="1" subjects_affected="1" subjects_at_risk="549"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Carotid Arteriosclerosis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="5527"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="551"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="545"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="550"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="549"/>
              </event>
              <event>
                <sub_title>Cerebral Haematoma</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="5527"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="551"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="545"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="550"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="549"/>
              </event>
              <event>
                <sub_title>Cerebral Infarction</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="5527"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="551"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="545"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="550"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="549"/>
              </event>
              <event>
                <sub_title>Lacunar Infarction</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="5527"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="551"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="545"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="550"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="549"/>
              </event>
              <event>
                <sub_title>Myasthenia Gravis</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="5527"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="551"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="545"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="550"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="549"/>
              </event>
              <event>
                <sub_title>Vascular Headache</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="5527"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="551"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="545"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="550"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="549"/>
              </event>
              <event>
                <sub_title>Cerebral Haemorrhage</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="5527"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="551"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="545"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="550"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="549"/>
              </event>
              <event>
                <sub_title>Diabetic Neuropathy</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="5527"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="551"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="545"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="550"/>
                <counts group_id="E5" events="1" subjects_affected="1" subjects_at_risk="549"/>
              </event>
              <event>
                <sub_title>Vertebrobasilar Insufficiency</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="5527"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="551"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="545"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="550"/>
                <counts group_id="E5" events="1" subjects_affected="1" subjects_at_risk="549"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Calculus Bladder</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="5527"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="551"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="545"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="550"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="549"/>
              </event>
              <event>
                <sub_title>Nephrolithiasis</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="5527"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="551"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="545"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="550"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="549"/>
              </event>
              <event>
                <sub_title>Renal Colic</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="5527"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="551"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="545"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="550"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="549"/>
              </event>
              <event>
                <sub_title>Nephrotic Syndrome</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="5527"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="551"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="545"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="550"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="549"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Diabetic Foot</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="5527"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="551"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="545"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="550"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="549"/>
              </event>
              <event>
                <sub_title>Drug Eruption</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="5527"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="551"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="545"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="550"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="549"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Surgical and medical procedures</title>
            <event_list>
              <event>
                <sub_title>Incisional Drainage</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="5527"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="551"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="545"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="550"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="549"/>
              </event>
              <event>
                <sub_title>Interventional Procedure</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="5527"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="551"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="545"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="550"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="549"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Vascular disorders</title>
            <event_list>
              <event>
                <sub_title>Essential Hypertension</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="5527"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="551"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="545"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="550"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="549"/>
              </event>
              <event>
                <sub_title>Hypertension</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="5527"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="551"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="545"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="550"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="549"/>
              </event>
              <event>
                <sub_title>Varicose Ulceration</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="5527"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="551"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="545"/>
                <counts group_id="E4" events="0" subjects_affected="0" subjects_at_risk="550"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="549"/>
              </event>
              <event>
                <sub_title>Peripheral Artery Stenosis</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="5527"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="551"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="545"/>
                <counts group_id="E4" events="1" subjects_affected="1" subjects_at_risk="550"/>
                <counts group_id="E5" events="0" subjects_affected="0" subjects_at_risk="549"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <default_vocab>MedDRA 18.0</default_vocab>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="66" subjects_at_risk="5527"/>
                <counts group_id="E2" subjects_affected="3" subjects_at_risk="551"/>
                <counts group_id="E3" subjects_affected="33" subjects_at_risk="545"/>
                <counts group_id="E4" subjects_affected="20" subjects_at_risk="550"/>
                <counts group_id="E5" subjects_affected="48" subjects_at_risk="549"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Metabolism and nutrition disorders</title>
            <event_list>
              <event>
                <sub_title>Hypoglycemia</sub_title>
                <counts group_id="E1" events="84" subjects_affected="66" subjects_at_risk="5527"/>
                <counts group_id="E2" events="5" subjects_affected="3" subjects_at_risk="551"/>
                <counts group_id="E3" events="51" subjects_affected="33" subjects_at_risk="545"/>
                <counts group_id="E4" events="35" subjects_affected="20" subjects_at_risk="550"/>
                <counts group_id="E5" events="72" subjects_affected="48" subjects_at_risk="549"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>The investigator agrees not to publish or publicly present any interim results of the study without the prior written consent of the sponsor. The investigator further agrees to provide to the sponsor 45 days prior to submission for publication or presentation, review copies of abstracts or manuscripts for publication that report any results of the study.</restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Senior Vice President, Global Clinical Development</name_or_title>
      <organization>Merck Sharp &amp; Dohme Corp.</organization>
      <phone>1-800-672-6372</phone>
      <email>ClinicalTrialsDisclosure@merck.com</email>
    </point_of_contact>
  </clinical_results>
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT01709305
org study id: 0431-313
nct id: NCT01709305
lead sponsor: 
has dmc: No
To assess the effect of adding acarbose or repaglinide or gliclazide to sitagliptin plus
      metformin, compared to adding glimepiride, on glycemic improvements in Type 2 Diabetes
      Mellitus (T2DM) participants who require the addition of a third oral anti-hyperglycemic
      agent (OAHA) according to China Guideline for Type 2 Diabetes. The three co-primary
      hypotheses are that after 24 weeks of treatment in phase 2, the mean change from baseline in
      hemoglobin A1c (A1c) in participants receiving either (1)acarbose or (2)repaglinide or
      (3)gliclazide added to sitagliptin and metformin combination is non-inferior to that of
      participants receiving glimepiride added to sitagliptin and metformin combination. The study
      would be declared successful if at least one of the three primary hypotheses was met.
Participants coming on study will be stabilized to a standardized metformin dose: this may
      take about 10 weeks, and then combination therapy with metformin + sitagliptin will begin
      during Phase 1 (Week 0 through Week 20). If a participant has already been on a stabilized
      metformin dose, they will start immediately on combination therapy with metformin +
      sitagliptin for 20 weeks (Phase 1).

      In Phase 2, participants who have failed to achieve adequate glycemic control (A1c ≥ 7% and ≤
      10% at Week 16 and fasting finger stick glucose ≥130 mg/dL and ≤280 mg/dL at Week 20) will be
      randomized to receive add-on therapy with glimepiride, repaglinide, acarbose, or gliclazide
      for 24 weeks (Week 20 through Week 44).
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Change From Phase 2 Baseline to Week 44 in Hemoglobin A1c (HbA1c) Levels (Phase 2)
time frame: Phase 2 Baseline (Week 20) and Week 44
description: HbA1c is blood marker used to report average blood glucose levels over prolonged periods of time and is reported as a percentage (%). Change from baseline reflects the Week 44 A1C minus baseline A1C. Baseline is defined as Visit 6/Week 20. If this measurement was unavailable, the Week 16 value was used. Change from baseline was based on the constrained longitudinal data analysis (cLDA) model including all available measurements from baseline through the last visit. The terms in the cLDA model include treatment, time in weeks (categorical), regions, and treatment-by-time interaction.
measure: Change From Phase 2 Baseline to Week 44 in Participant Body Weight (Phase 2)
time frame: Phase 2 Baseline (Week 20), Week 44
description: Change from baseline in body weight in Phase 2 was reported. Change from baseline reflects the Week 44 body weight minus baseline body weight. Baseline is defined as Visit 6/Week 20. If this measurement was unavailable, the Week 16 value was used.
measure: Percentage of Participants With Hypoglycemia Events (Phase 2)
time frame: From Week 20 through Week 44
description: Hypoglycemia events represent epidsodes symptomatic of hypoglycemia (e.g., weakness, dizziness, shakiness, increased sweating, palpitations, or confusion) and/or finger stick glucose values of ≤70 mg/dL (3.9 mmol/L). The percentage of participants with hypoglycemia events was reported.
measure: Percentage of Participants With a Gastrointestinal (GI) AE of Nausea (Phase 2)
time frame: From Week 20 through Week 44
description: The percentage of participants with a GI AE of "nausea" was reported.
measure: Percentage of Participants With a GI AE of Vomiting (Phase 2)
time frame: From Week 20 through Week 44
description: The percentage of participants with a GI AE of "vomiting" was reported.
measure: Percentage of Participants With a GI AE of Diarrhea (Phase 2)
time frame: From Week 20 through Week 44
description: The percentage of participants with a GI AE of "diarrhea" was reported.
measure: Percentage of Participants With a GI AE of Abdominal Pain (Phase 2)
time frame: From Week 20 through Week 44
description: The percentage of participants with a GI AE of "abdominal pain" was reported.
arm group label: Metformin + Sitagliptin + Glimepiride
arm group type: Active Comparator
description: During Phase 2, participants receive up to 6 mg glimepiride daily as an add-on to metformin + sitagliptin combination therapy for 24 weeks (Week 20 through Week 44).
arm group label: Metformin + Sitagliptin + Repaglinide
arm group type: Experimental
description: During Phase 2, participants receive up to 16 mg repaglinide daily as an add-on to metformin + sitagliptin combination therapy for 24 weeks (Week 20 through Week 44).
arm group label: Metformin + Sitagliptin + Acarbose
arm group type: Experimental
description: During Phase 2, participants receive 50-100 mg acarbose three times daily as an add-on to metformin + sitagliptin combination therapy for 24 weeks (Week 20 through Week 44).
arm group label: Metformin + Sitagliptin + Gliclazide
arm group type: Experimental
description: During Phase 2, participants receive 30-120 mg gliclazide daily as an add-on to metformin + sitagliptin combination therapy for 24 weeks (Week 20 through Week 44).
intervention type: Drug
intervention name: Metformin
description: Metformin, 500 mg or 850 mg oral tablets, twice or three times a day (BID or TID) for a total dose of at least 1500 mg daily; administered with food.
arm group label: Metformin + Sitagliptin + Acarbose
arm group label: Metformin + Sitagliptin + Gliclazide
arm group label: Metformin + Sitagliptin + Glimepiride
arm group label: Metformin + Sitagliptin + Repaglinide
other name: Fortamet®
other name: Glucophage®
other name: Glucophage® XR
other name: Glumetza®
other name: Riomet®
other name: Metgluco®
other name: Glycoran®
intervention type: Drug
intervention name: Sitagliptin
description: Sitagliptin, 100 mg oral tablet, once daily (QD); administered with or without food
arm group label: Metformin + Sitagliptin + Acarbose
arm group label: Metformin + Sitagliptin + Gliclazide
arm group label: Metformin + Sitagliptin + Glimepiride
arm group label: Metformin + Sitagliptin + Repaglinide
other name: Januvia®
other name: Tesavel®
other name: Xelevia®
other name: Ristaben®
intervention type: Drug
intervention name: Acarbose
description: Acarbose, 50 mg oral tablets, TID (150 mg total daily dose); administered with the first bite of each main meal.
arm group label: Metformin + Sitagliptin + Acarbose
other name: Precose®
other name: Glucobay™
intervention type: Drug
intervention name: Repaglinide
description: Repaglinide, 0.5 mg and/or 1 mg oral tablets, TID (up to 16 mg daily); administered within 30 minutes of each meal.
arm group label: Metformin + Sitagliptin + Repaglinide
other name: Prandin®
other name: Fulaidi™
intervention type: Drug
intervention name: Glimepiride
description: Glimepiride, 1 mg and/or 2 mg oral tablets, QD (up to 6 mg daily); administered before the first main meal of the day
arm group label: Metformin + Sitagliptin + Glimepiride
other name: Amaryl®
other name: Glimy
intervention type: Drug
intervention name: Gliclazide
description: Gliclazide, 30 mg oral tablets, QD or BID (30 mg to 120 mg total daily dose); administered with meal.
arm group label: Metformin + Sitagliptin + Gliclazide
other name: Diamicron MR™
criteria: 
gender: All
minimum age: 18 Years
maximum age: 75 Years
healthy volunteers: No
last name: Medical Director
role: Study Director
affiliation: Merck Sharp & Dohme LLC
country: China
citation: Xu W, Mu Y, Zhao J, Zhu D, Ji Q, Zhou Z, Yao B, Mao A, Engel SS, Zhao B, Bi Y, Zeng L, Ran X, Lu J, Ji L, Yang W, Jia W, Weng J. Efficacy and safety of metformin and sitagliptin based triple antihyperglycemic therapy (STRATEGY): a multicenter, randomized, controlled, non-inferiority clinical trial. Sci China Life Sci. 2017 Mar;60(3):225-238. doi: 10.1007/s11427-016-0409-7. Epub 2017 Feb 7.
PMID: 28271251
responsible party type: Sponsor
mesh term: Diabetes Mellitus
mesh term: Diabetes Mellitus, Type 2
mesh term: Metformin
mesh term: Sitagliptin Phosphate
mesh term: Glimepiride
mesh term: Acarbose
mesh term: Repaglinide
mesh term: Gliclazide
sharing ipd: Yes
ipd description: https://www.merck.com/clinical-trials/pdf/ProcedureAccessClinicalTrialData.pdf
ipd url: http://engagezone.msd.com/ds_documentation.php
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 