<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/NCT03233178</url>
  </required_header>
  <id_info>
    <org_study_id>ALT</org_study_id>
    <nct_id>NCT03233178</nct_id>
  </id_info>
  <brief_title>Measurement of Alanine Aminotransaminase (ALT) Following Initiation of Antidiabetic Agents in Patients With Type 2 Diabetes in a Real-world Clinical Setting: a Retrospective Cohort Study</brief_title>
  <acronym>ALT</acronym>
  <official_title>Measurement of Alanine Aminotransaminase (ALT) Following Initiation of Antidiabetic Agents in Patients With Type 2 Diabetes in a Real-world Clinical Setting: a Retrospective Cohort Study</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>LMC Diabetes &amp; Endocrinology Ltd.</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>LMC Diabetes &amp; Endocrinology Ltd.</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The primary objective of this study is to investigate the change in Alanine Aminotransaminase&#xD;
      (ALT) in patients with Type 2 Diabetes Mellitus (T2DM) initiating Sodium Glucose&#xD;
      Cotransporter 2 (SGLT2) inhibitors, liraglutide, or sitagliptin, compared to a control group&#xD;
      of patients who did not initiate a new antihyperglycemic therapy. The hypothesis is that&#xD;
      patients using Sodium Glucose Cotransporter 2 inhibitors (SGLT2i) will achieve a greater&#xD;
      reduction in ALT compared to the control group.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Non-alcoholic fatty liver disease (NAFLD) is very commonly associated with type 2 diabetes&#xD;
      mellitus (T2DM) 1. Alanine aminotransferase (ALT) is a common biomarker used to predict&#xD;
      levels of NAFLD. The only class of antidiabetic agents thought to be protective of NAFLD are&#xD;
      thiazolidinedione's. Few studies have investigated the effect of other antidiabetic agents on&#xD;
      bio markers of fatty liver disease 2. A recent pooled analysis of randomized controlled&#xD;
      trials that compared canagliflozin to either placebo or sitagliptin showed significant&#xD;
      reductions in ALT in the canagliflozin cohorts, which were fully explained by HbA1c and body&#xD;
      weight reductions 3. As well, a study that compared ALT change in patients initiating&#xD;
      liraglutide found significant reductions in ALT, which was strongly correlated to reduction&#xD;
      in body weight 4. However, the effect of different antidiabetic agents on bio markers of&#xD;
      fatty liver disease is not well characterized.&#xD;
&#xD;
      The primary objective of this study is to investigate the change in ALT in patients with T2DM&#xD;
      initiating SGLT2 inhibitors, liraglutide, or sitagliptin, compared to a control group of&#xD;
      patients who did not initiate a new antihyperglycemic therapy. The hypothesis is that&#xD;
      patients using SGLT2i will achieve a greater reduction in ALT compared to the control group.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">January 2017</start_date>
  <completion_date type="Actual">June 2017</completion_date>
  <primary_completion_date type="Actual">June 2017</primary_completion_date>
  <study_type>Observational</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <observational_model>Cohort</observational_model>
    <time_perspective>Retrospective</time_perspective>
  </study_design_info>
  <primary_outcome>
    <measure>Change in ALT in patients with T2DM initiating SGLT2 inhibitors, Liraglutide or Sitagliptin compared to control</measure>
    <time_frame>1 year</time_frame>
    <description>Change in ALT in patients with T2DM initiating SGLT2 inhibitors, Liraglutide or Sitagliptin compared to control</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change in Hemoglobin A1c from baseline to follow-up</measure>
    <time_frame>1 year</time_frame>
    <description>Change in HbA1c from baseline to follow-up</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Fasting Plasma Glucose from baseline to follow-up</measure>
    <time_frame>1 year</time_frame>
    <description>Change in Fasting Plasma Glucose from baseline to follow-up</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in body weight from baseline to follow-up</measure>
    <time_frame>1 year</time_frame>
    <description>Change in body weight from baseline to follow-up</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Body Mass Index (BMI) from baseline to follow-up</measure>
    <time_frame>1 year</time_frame>
    <description>Change in BMI from baseline to follow-up</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Waist Circumference (WC) from baseline to follow-up</measure>
    <time_frame>1 year</time_frame>
    <description>Change in WC from baseline to follow-up</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in triglycerides from baseline to follow-up</measure>
    <time_frame>1 year</time_frame>
    <description>Change in triglycerides from baseline to follow-up</description>
  </secondary_outcome>
  <number_of_groups>4</number_of_groups>
  <enrollment type="Actual">4000</enrollment>
  <condition>T2DM (Type 2 Diabetes Mellitus)</condition>
  <condition>Fatty Liver</condition>
  <condition>NAFLD</condition>
  <arm_group>
    <arm_group_label>SGLT2</arm_group_label>
    <description>Patients initiating SGLT2 inhibitors</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Liraglutide</arm_group_label>
    <description>Patients initiation liraglutide</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Sitagliptin</arm_group_label>
    <description>Patients initiating sitagliptin</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Control Group</arm_group_label>
    <description>Patients who did not initiate any new anti-hyperglycemic treatment</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Non-interventional</intervention_name>
    <arm_group_label>Control Group</arm_group_label>
    <arm_group_label>Liraglutide</arm_group_label>
    <arm_group_label>SGLT2</arm_group_label>
    <arm_group_label>Sitagliptin</arm_group_label>
  </intervention>
  <eligibility>
    <study_pop>
      <textblock>
        This study will include patients with T2DM who are patients at LMC Diabetes &amp;&#xD;
        Endocrinology. Patients will be included in the treatment cohorts if they initiated&#xD;
        canagliflozin, dapagliflozin, liraglutide or sitagliptin, between January 2011 and December&#xD;
        2015, and did not discontinue the treatment prior to 6 weeks of being on the medication.&#xD;
        The control group will include patients with T2DM who are patients at LMC Diabetes &amp;&#xD;
        Endocrinology, and who did not initiate any new diabetes treatment between June 2014 and&#xD;
        June 2015.&#xD;
      </textblock>
    </study_pop>
    <sampling_method>Probability Sample</sampling_method>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Diagnosis of T2DM based upon historical clinical diagnosis&#xD;
&#xD;
          -  Patients who initiated canagliflozin, dapagliflozin, liraglutide or sitagliptin by an&#xD;
             LMC physician between January 2011 and December 2015, or patients who did not initiate&#xD;
             a new diabetes therapy between June 2014 and June 2015.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Diagnosis of type 1 diabetes&#xD;
&#xD;
          -  Patients who switched to one of the study treatments from another medication of the&#xD;
             same medication class&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>LMC Brampton</name>
      <address>
        <city>Brampton</city>
        <state>Ontario</state>
        <zip>L6S 0C9</zip>
        <country>Canada</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Canada</country>
  </location_countries>
  <verification_date>July 2017</verification_date>
  <study_first_submitted>July 20, 2017</study_first_submitted>
  <study_first_submitted_qc>July 27, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">July 28, 2017</study_first_posted>
  <last_update_submitted>July 27, 2017</last_update_submitted>
  <last_update_submitted_qc>July 27, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">July 28, 2017</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>Fatty Liver</mesh_term>
    <mesh_term>Diabetes Mellitus</mesh_term>
    <mesh_term>Diabetes Mellitus, Type 2</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</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/NCT03233178
org study id: ALT
nct id: NCT03233178
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
The primary objective of this study is to investigate the change in Alanine Aminotransaminase
      (ALT) in patients with Type 2 Diabetes Mellitus (T2DM) initiating Sodium Glucose
      Cotransporter 2 (SGLT2) inhibitors, liraglutide, or sitagliptin, compared to a control group
      of patients who did not initiate a new antihyperglycemic therapy. The hypothesis is that
      patients using Sodium Glucose Cotransporter 2 inhibitors (SGLT2i) will achieve a greater
      reduction in ALT compared to the control group.
Non-alcoholic fatty liver disease (NAFLD) is very commonly associated with type 2 diabetes
      mellitus (T2DM) 1. Alanine aminotransferase (ALT) is a common biomarker used to predict
      levels of NAFLD. The only class of antidiabetic agents thought to be protective of NAFLD are
      thiazolidinedione's. Few studies have investigated the effect of other antidiabetic agents on
      bio markers of fatty liver disease 2. A recent pooled analysis of randomized controlled
      trials that compared canagliflozin to either placebo or sitagliptin showed significant
      reductions in ALT in the canagliflozin cohorts, which were fully explained by HbA1c and body
      weight reductions 3. As well, a study that compared ALT change in patients initiating
      liraglutide found significant reductions in ALT, which was strongly correlated to reduction
      in body weight 4. However, the effect of different antidiabetic agents on bio markers of
      fatty liver disease is not well characterized.

      The primary objective of this study is to investigate the change in ALT in patients with T2DM
      initiating SGLT2 inhibitors, liraglutide, or sitagliptin, compared to a control group of
      patients who did not initiate a new antihyperglycemic therapy. The hypothesis is that
      patients using SGLT2i will achieve a greater reduction in ALT compared to the control group.
observational model: Cohort
time perspective: Retrospective
measure: Change in ALT in patients with T2DM initiating SGLT2 inhibitors, Liraglutide or Sitagliptin compared to control
time frame: 1 year
description: Change in ALT in patients with T2DM initiating SGLT2 inhibitors, Liraglutide or Sitagliptin compared to control
measure: Change in Hemoglobin A1c from baseline to follow-up
time frame: 1 year
description: Change in HbA1c from baseline to follow-up
measure: Change in Fasting Plasma Glucose from baseline to follow-up
time frame: 1 year
description: Change in Fasting Plasma Glucose from baseline to follow-up
measure: Change in body weight from baseline to follow-up
time frame: 1 year
description: Change in body weight from baseline to follow-up
measure: Change in Body Mass Index (BMI) from baseline to follow-up
time frame: 1 year
description: Change in BMI from baseline to follow-up
measure: Change in Waist Circumference (WC) from baseline to follow-up
time frame: 1 year
description: Change in WC from baseline to follow-up
measure: Change in triglycerides from baseline to follow-up
time frame: 1 year
description: Change in triglycerides from baseline to follow-up
arm group label: SGLT2
description: Patients initiating SGLT2 inhibitors
arm group label: Liraglutide
description: Patients initiation liraglutide
arm group label: Sitagliptin
description: Patients initiating sitagliptin
arm group label: Control Group
description: Patients who did not initiate any new anti-hyperglycemic treatment
intervention type: Other
intervention name: Non-interventional
arm group label: Control Group
arm group label: Liraglutide
arm group label: SGLT2
arm group label: Sitagliptin
study pop: 
sampling method: Probability Sample
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
facility: 
country: Canada
responsible party type: Sponsor
mesh term: Fatty Liver
mesh term: Diabetes Mellitus
mesh term: Diabetes Mellitus, Type 2
sharing ipd: No