<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/NCT02250794</url>
  </required_header>
  <id_info>
    <org_study_id>14042807</org_study_id>
    <nct_id>NCT02250794</nct_id>
  </id_info>
  <brief_title>Metformin and Sitagliptin Therapy for Adult Patients With Type 2 Diabetes Admitted to the General Medical Unit</brief_title>
  <official_title>Metformin and Sitagliptin Therapy for Adult Patients With Type 2 Diabetes Admitted to the General Medical Unit</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Rush University Medical Center</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Rush University Medical Center</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to test whether a combination of two pills commonly used to&#xD;
      treat outpatient diabetes called metformin and sitagliptin (januvia) could provide successful&#xD;
      control of blood sugar levels in patients with type 2 diabetes during hospitalization for the&#xD;
      treatment of a general medical condition. Both metformin and sitagliptin are currently&#xD;
      approved by the Food and Drug Administration for the treatment of type 2 diabetes, but little&#xD;
      experience exists for their use in hospitalized patients. The current standard practice is to&#xD;
      use insulin injections to control blood sugar in hospitalized patients with type 2 diabetes.&#xD;
      This study will compare the use of metformin tablets twice per day along with sitagliptin&#xD;
      tablets once per day with daily insulin injections in patients with type 2 diabetes during&#xD;
      hospitalization, and will study how well the blood sugar levels are controlled.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      We propose a trial to evaluate whether in-hospital glycemic control, as measured by mean&#xD;
      daily glucose concentration and frequency of hypoglycemic events, is different between&#xD;
      treatment with metformin and sitagliptin combination and treatment with glargine insulin once&#xD;
      daily and rapid-acting insulin analog with meals in patients with type 2 diabetes.&#xD;
      Hyperglycemia is associated with increased mortality, prolonged hospitalization and increased&#xD;
      complications such as infection (1). Consensus guidelines recommend long-acting basal insulin&#xD;
      and meal-time bolus insulin therapy for inpatient blood glucose management. These basal bolus&#xD;
      regimens are labor intensive, require multiple injections each day, and can cause&#xD;
      hypoglycemia. A study at our institution of patients admitted to the hospital and treated&#xD;
      with our basal bolus insulin protocol found the incidence of hypoglycemia (blood glucose less&#xD;
      than 70 mg/dl) to be 20% of all patient stays (2). A strategy for inpatient blood glucose&#xD;
      management with less risk of hypoglycemia is needed.&#xD;
&#xD;
      We propose a trial of the use of two oral medications metformin and sitagliptin that lower&#xD;
      blood sugar without the risk of hypoglycemia. Metformin is first-line therapy for outpatient&#xD;
      management of type 2 diabetes. It has long-standing evidence of safety and efficacy. It&#xD;
      decreases hepatic glucose production and increases insulin-mediated glucose utilization in&#xD;
      the muscle and the liver. A Cochrane Review of 29 trials of metformin as monotherapy compared&#xD;
      with other oral agents, insulin, diet, or placebo showed a reduction in cardiovascular events&#xD;
      and all-cause mortality with metformin (3).&#xD;
&#xD;
      Sitagliptin is a Dipeptidyl-peptidase-4 (DPP-4) inhibitor approved by the FDA as monotherapy&#xD;
      or in combination with metformin for the treatment of type 2 diabetes. Metformin and&#xD;
      sitagliptin are active within 24 hours of initiation and do not cause hypoglycemia.&#xD;
      Sitagliptin works by slowing the inactivation of glucagon-like peptide-1 (GLP-1). GLP-1&#xD;
      stimulates glucose dependent secretion of endogenous insulin with meals.&#xD;
&#xD;
      A recent preliminary study supports the use of sitagliptin for inpatient glucose management.&#xD;
      This trial included 90 patients with type 2 diabetes admitted to general medicine and surgery&#xD;
      services. It randomized patients to one of three groups: sitagliptin alone, sitagliptin plus&#xD;
      long-acting insulin (glargine), or a basal bolus insulin regimen. The study selected for&#xD;
      patients with mild to moderate diabetes by including only patients with diabetes controlled&#xD;
      by diet alone, any combination of oral antidiabetic agents, or a total daily insulin dose ≤&#xD;
      0.4 units/kg prior to admission. Patients were eligible if their blood sugar was 140 - 400&#xD;
      mg/dl. Patients in all three groups received supplemental (correction) doses of rapid-acting&#xD;
      insulin before meals and bedtime for blood glucose &gt;140 mg/dL. Glycemic control improved&#xD;
      similarly in all treatment groups, but 100% of the patients in the sitagliptin alone group&#xD;
      required one or more injections of rapid-acting insulin to correct hyperglycemia (4). This&#xD;
      result suggests that sitagliptin alone is insufficient therapy for treating hyperglycemia in&#xD;
      this population. We will recruit a similar population of patients, and we will add metformin&#xD;
      for improved blood sugar control. Our sitagliptin and metformin group will not receive&#xD;
      supplemental doses of rapid-acting insulin as the purpose of this trial is to evaluate a&#xD;
      regimen without the risk of hypoglycemia.&#xD;
&#xD;
      Metformin is safe in patients with adequate renal function. The current prescribing&#xD;
      information for metformin is that its use is permitted with a serum creatinine ≤ 1.4 mg/dL in&#xD;
      women and ≤ 1.5 mg/dL in men which is equivalent to a GFR ≥ 60 ml/min (5). It is excreted by&#xD;
      the kidneys and therefore can potentially accumulate in patients with renal failure.&#xD;
      Metformin works by inhibiting gluconeogenesis-a process that utilizes lactic acid to produce&#xD;
      glucose. Thus, with accumulation of this medication, it could predispose patients to lactic&#xD;
      acidosis. The incidence of lactic acidosis with metformin is extremely low. A systematic&#xD;
      review of 347 randomized trials and prospective cohort studies representing 70,490&#xD;
      patient-years of metformin use and 55,451 patient-years in the non-metformin group revealed&#xD;
      no cases of lactic acidosis. Almost half of the studies allowed inclusion of patients with a&#xD;
      serum creatinine above 1.5 mg/dL, and 97% of the studies allowed inclusion of patients with&#xD;
      at least one contraindication to metformin therapy (6). Another trial evaluated the risk of&#xD;
      lactic acidosis with metformin in 393 patients with renal insufficiency, with serum&#xD;
      creatinine levels of 1.5 to 2.5 mg/dl (mean level 1.8 mg/dl) and found no cases of lactic&#xD;
      acidosis over four years of the trial duration (7).&#xD;
&#xD;
      Most cases of lactic acidosis in patients taking metformin have been associated with shock or&#xD;
      other tissue hypoxia. Elevated lactate in these patients may not be related to metformin.&#xD;
      This is supported by the fact that lactic acidosis occurs as frequently in metformin users as&#xD;
      users of other anti-diabetes medications (8). Also, metformin levels do not correlate with&#xD;
      lactate levels or mortality suggesting that the underlying disease is more likely the cause&#xD;
      of the acidosis than metformin (9). However this theoretical concern for an exceedingly rare&#xD;
      complication has excluded metformin from use in hospitalized patients.&#xD;
&#xD;
      The recognition of the rarity of lactic acidosis among users of metformin with renal&#xD;
      insufficiency has changed recommendations to allow for its use in patients with mild to&#xD;
      moderate renal insufficiency. Current guidelines use an estimated GFR (eGFR) which is a more&#xD;
      accurate approximation of renal function than serum creatinine. The current recommendation of&#xD;
      the American Diabetes Association states that metformin can be used at full doses (2000&#xD;
      mg/day) as long as eGFR &gt; 45 ml/min and serum creatinine is monitored. If the eGFR is &lt;&#xD;
      45ml/min, then a maximal dose of 1000 mg/day is advised, with serum creatinine monitoring.&#xD;
      Metformin should not be used if the eGFR is &lt; 30 ml/min (10).&#xD;
&#xD;
      The American College of Radiology has recently updated their guidelines for the use of&#xD;
      metformin in patients receiving IV contrast media (11). A prior guideline recommended holding&#xD;
      metformin for 4 days surrounding IV contrast administration to evaluate for contrast-induced&#xD;
      acute kidney injury. This guideline contributed to the practice of discontinuing metformin&#xD;
      during hospitalization due to the commonness of radiology studies using IV contrast. There is&#xD;
      no drug interaction between metformin and contrast media nor is there any effect of metformin&#xD;
      on renal function. Given the risk of contrast-induced acute kidney injury is very low in&#xD;
      patients with normal renal function and no co-morbidities, the revised (2013) American&#xD;
      College of Radiology guidelines recommend that metformin can be continued without the need to&#xD;
      evaluate renal function following contrast media. In the presence of co-morbidities that&#xD;
      increase the risk for developing acidosis (liver dysfunction, alcohol abuse, heart failure,&#xD;
      myocardial or peripheral muscle ischemia, sepsis or severe infection), the new guidelines&#xD;
      recommend holding metformin for two days after IV contrast administration. Our study will&#xD;
      only include patients without these co-morbidities and with normal renal function (eGFR &gt; 60&#xD;
      ml/min). All subjects will have serum creatinine measured daily, and metformin will be&#xD;
      discontinued in the event of acute kidney injury.&#xD;
&#xD;
      Since metformin is safe and effective for glucose management in patients with type 2 diabetes&#xD;
      and normal renal function, we propose its continuation during hospitalization. This study&#xD;
      will include adult patients with type 2 diabetes currently treated with metformin alone or in&#xD;
      combination with other anti-diabetic agents including low dose insulin. All subjects will&#xD;
      have normal renal function (eGFR&gt;60 ml/min) and no comorbidities that increase the risk for&#xD;
      acidosis. This prospective, randomized controlled trial will compare metformin and&#xD;
      sitagliptin (which cannot cause hypoglycemia) to usual insulin therapy, which is known to&#xD;
      cause hypoglycemia. This study has possible implications for improving the safety of therapy&#xD;
      for hospitalized patients with type 2 diabetes.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Withdrawn</overall_status>
  <why_stopped>
    No subjects enrolled.&#xD;
  </why_stopped>
  <start_date>October 2014</start_date>
  <completion_date type="Actual">May 2015</completion_date>
  <primary_completion_date type="Actual">May 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>mean blood glucose for the duration of the hospital stay</measure>
    <time_frame>duration of hospital stay</time_frame>
    <description>Participants will be followed for the duration of the hospital stay, an expected average of 5 days.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>frequency of hypoglycemia</measure>
    <time_frame>duration of hospital stay</time_frame>
    <description>Participants will be followed for the duration of the hospital stay, an expected average of 5 days. The outcome is the percent of patients having any blood glucose value less than 70 mg/dl during their hospital stay.</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Acute kidney injury</measure>
    <time_frame>duration of hospital stay</time_frame>
    <description>Participants will be followed for the duration of the hospital stay, an expected average of 5 days. The outcome is the percent of patients who develop acute kidney injury during their hospital stay. Acute kidney injury is defined as an absolute increase in the serum creatinine concentration of ≥ 0.3 mg/dL from baseline or a percentage increase in the serum creatinine concentration of ≥ 50%</description>
  </other_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">0</enrollment>
  <condition>Type 2 Diabetes Mellitus</condition>
  <arm_group>
    <arm_group_label>insulin glargine and insulin lispro</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>insulin glargine 0.3 units per kg and insulin lispro 0.1 units per kg with each meal</description>
  </arm_group>
  <arm_group>
    <arm_group_label>metformin and sitagliptin</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>metformin 750 mg PO twice daily and sitagliptin 100 mg PO once daily</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>metformin and sitagliptin</intervention_name>
    <description>metformin 750 mg PO twice daily</description>
    <arm_group_label>metformin and sitagliptin</arm_group_label>
    <other_name>glucophage</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>insulin glargine and insulin lispro</intervention_name>
    <description>insulin glargine given once daily</description>
    <arm_group_label>insulin glargine and insulin lispro</arm_group_label>
    <other_name>lantus insulin</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>metformin and sitagliptin</intervention_name>
    <description>sitagliptin 100 mg PO once daily</description>
    <arm_group_label>metformin and sitagliptin</arm_group_label>
    <other_name>Januvia</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>insulin glargine and insulin lispro</intervention_name>
    <description>insulin lispro given three times daily with meals</description>
    <arm_group_label>insulin glargine and insulin lispro</arm_group_label>
    <other_name>humalog insulin</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Males or females between the ages of 18 and 80 years admitted to a general medicine&#xD;
             services not requiring intensive care and not expected to require surgery.&#xD;
&#xD;
          2. Type 2 diabetes for ≥ 3 months treated with metformin (≥ 1000 mg/day) alone or&#xD;
             metformin (≥ 1000 mg/day) with glimepiride, glyburide, glipizide, saxagliptin,&#xD;
             sitagliptin, linagliptin, alogliptin, repaglinide, nateglinide, pioglitazone,&#xD;
             exenatide, liraglutide, or a total daily dose of insulin ≤ 0.4 units/kg/day prior to&#xD;
             admission.&#xD;
&#xD;
          3. Blood glucose&gt;140 mg and &lt; 400 mg/dL&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Acute critical illness expected to require admission to a critical care unit&#xD;
&#xD;
          2. Patients expected to require major surgery (requiring general anesthesia)&#xD;
&#xD;
          3. Patients expected to require gastrointestinal suction&#xD;
&#xD;
          4. Patients treated with less than 1000 mg/day of metformin prior to admission&#xD;
&#xD;
          5. Patients expected to be kept nothing by mouth (NPO) for &gt;24-48 hours after admission&#xD;
&#xD;
          6. Patients with impaired renal function estimated GFR less than 60 ml/min based on the&#xD;
             Modification of Diet in Renal Disease (MDRD) Study equation.&#xD;
&#xD;
          7. Clinically significant liver dysfunction or current alcohol abuse&#xD;
&#xD;
          8. Uncompensated heart failure&#xD;
&#xD;
          9. Myocardial or peripheral muscle ischemia&#xD;
&#xD;
         10. Sepsis or severe infection&#xD;
&#xD;
         11. Treatment with glucocorticoid greater than prednisone 5 mg daily or the equivalent&#xD;
&#xD;
         12. Mental condition rendering the subject unable to understand the nature, scope, and&#xD;
             possible consequences of the study&#xD;
&#xD;
         13. Pregnancy or breast-feeding at time of enrollment into the study&#xD;
&#xD;
             -&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>80 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <verification_date>October 2021</verification_date>
  <study_first_submitted>September 18, 2014</study_first_submitted>
  <study_first_submitted_qc>September 23, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 26, 2014</study_first_posted>
  <last_update_submitted>October 4, 2021</last_update_submitted>
  <last_update_submitted_qc>October 4, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">October 11, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>diabetes mellitus</keyword>
  <keyword>inpatient management</keyword>
  <keyword>metformin</keyword>
  <keyword>sitagliptin</keyword>
  <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>Insulin</mesh_term>
    <mesh_term>Insulin, Globin Zinc</mesh_term>
    <mesh_term>Metformin</mesh_term>
    <mesh_term>Insulin Glargine</mesh_term>
    <mesh_term>Sitagliptin Phosphate</mesh_term>
    <mesh_term>Insulin Lispro</mesh_term>
  </intervention_browse>
  <!-- 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/NCT02250794
org study id: 14042807
nct id: NCT02250794
lead sponsor: 
has dmc: No
The purpose of this study is to test whether a combination of two pills commonly used to
      treat outpatient diabetes called metformin and sitagliptin (januvia) could provide successful
      control of blood sugar levels in patients with type 2 diabetes during hospitalization for the
      treatment of a general medical condition. Both metformin and sitagliptin are currently
      approved by the Food and Drug Administration for the treatment of type 2 diabetes, but little
      experience exists for their use in hospitalized patients. The current standard practice is to
      use insulin injections to control blood sugar in hospitalized patients with type 2 diabetes.
      This study will compare the use of metformin tablets twice per day along with sitagliptin
      tablets once per day with daily insulin injections in patients with type 2 diabetes during
      hospitalization, and will study how well the blood sugar levels are controlled.
We propose a trial to evaluate whether in-hospital glycemic control, as measured by mean
      daily glucose concentration and frequency of hypoglycemic events, is different between
      treatment with metformin and sitagliptin combination and treatment with glargine insulin once
      daily and rapid-acting insulin analog with meals in patients with type 2 diabetes.
      Hyperglycemia is associated with increased mortality, prolonged hospitalization and increased
      complications such as infection (1). Consensus guidelines recommend long-acting basal insulin
      and meal-time bolus insulin therapy for inpatient blood glucose management. These basal bolus
      regimens are labor intensive, require multiple injections each day, and can cause
      hypoglycemia. A study at our institution of patients admitted to the hospital and treated
      with our basal bolus insulin protocol found the incidence of hypoglycemia (blood glucose less
      than 70 mg/dl) to be 20% of all patient stays (2). A strategy for inpatient blood glucose
      management with less risk of hypoglycemia is needed.

      We propose a trial of the use of two oral medications metformin and sitagliptin that lower
      blood sugar without the risk of hypoglycemia. Metformin is first-line therapy for outpatient
      management of type 2 diabetes. It has long-standing evidence of safety and efficacy. It
      decreases hepatic glucose production and increases insulin-mediated glucose utilization in
      the muscle and the liver. A Cochrane Review of 29 trials of metformin as monotherapy compared
      with other oral agents, insulin, diet, or placebo showed a reduction in cardiovascular events
      and all-cause mortality with metformin (3).

      Sitagliptin is a Dipeptidyl-peptidase-4 (DPP-4) inhibitor approved by the FDA as monotherapy
      or in combination with metformin for the treatment of type 2 diabetes. Metformin and
      sitagliptin are active within 24 hours of initiation and do not cause hypoglycemia.
      Sitagliptin works by slowing the inactivation of glucagon-like peptide-1 (GLP-1). GLP-1
      stimulates glucose dependent secretion of endogenous insulin with meals.

      A recent preliminary study supports the use of sitagliptin for inpatient glucose management.
      This trial included 90 patients with type 2 diabetes admitted to general medicine and surgery
      services. It randomized patients to one of three groups: sitagliptin alone, sitagliptin plus
      long-acting insulin (glargine), or a basal bolus insulin regimen. The study selected for
      patients with mild to moderate diabetes by including only patients with diabetes controlled
      by diet alone, any combination of oral antidiabetic agents, or a total daily insulin dose ≤
      0.4 units/kg prior to admission. Patients were eligible if their blood sugar was 140 - 400
      mg/dl. Patients in all three groups received supplemental (correction) doses of rapid-acting
      insulin before meals and bedtime for blood glucose >140 mg/dL. Glycemic control improved
      similarly in all treatment groups, but 100% of the patients in the sitagliptin alone group
      required one or more injections of rapid-acting insulin to correct hyperglycemia (4). This
      result suggests that sitagliptin alone is insufficient therapy for treating hyperglycemia in
      this population. We will recruit a similar population of patients, and we will add metformin
      for improved blood sugar control. Our sitagliptin and metformin group will not receive
      supplemental doses of rapid-acting insulin as the purpose of this trial is to evaluate a
      regimen without the risk of hypoglycemia.

      Metformin is safe in patients with adequate renal function. The current prescribing
      information for metformin is that its use is permitted with a serum creatinine ≤ 1.4 mg/dL in
      women and ≤ 1.5 mg/dL in men which is equivalent to a GFR ≥ 60 ml/min (5). It is excreted by
      the kidneys and therefore can potentially accumulate in patients with renal failure.
      Metformin works by inhibiting gluconeogenesis-a process that utilizes lactic acid to produce
      glucose. Thus, with accumulation of this medication, it could predispose patients to lactic
      acidosis. The incidence of lactic acidosis with metformin is extremely low. A systematic
      review of 347 randomized trials and prospective cohort studies representing 70,490
      patient-years of metformin use and 55,451 patient-years in the non-metformin group revealed
      no cases of lactic acidosis. Almost half of the studies allowed inclusion of patients with a
      serum creatinine above 1.5 mg/dL, and 97% of the studies allowed inclusion of patients with
      at least one contraindication to metformin therapy (6). Another trial evaluated the risk of
      lactic acidosis with metformin in 393 patients with renal insufficiency, with serum
      creatinine levels of 1.5 to 2.5 mg/dl (mean level 1.8 mg/dl) and found no cases of lactic
      acidosis over four years of the trial duration (7).

      Most cases of lactic acidosis in patients taking metformin have been associated with shock or
      other tissue hypoxia. Elevated lactate in these patients may not be related to metformin.
      This is supported by the fact that lactic acidosis occurs as frequently in metformin users as
      users of other anti-diabetes medications (8). Also, metformin levels do not correlate with
      lactate levels or mortality suggesting that the underlying disease is more likely the cause
      of the acidosis than metformin (9). However this theoretical concern for an exceedingly rare
      complication has excluded metformin from use in hospitalized patients.

      The recognition of the rarity of lactic acidosis among users of metformin with renal
      insufficiency has changed recommendations to allow for its use in patients with mild to
      moderate renal insufficiency. Current guidelines use an estimated GFR (eGFR) which is a more
      accurate approximation of renal function than serum creatinine. The current recommendation of
      the American Diabetes Association states that metformin can be used at full doses (2000
      mg/day) as long as eGFR > 45 ml/min and serum creatinine is monitored. If the eGFR is <
      45ml/min, then a maximal dose of 1000 mg/day is advised, with serum creatinine monitoring.
      Metformin should not be used if the eGFR is < 30 ml/min (10).

      The American College of Radiology has recently updated their guidelines for the use of
      metformin in patients receiving IV contrast media (11). A prior guideline recommended holding
      metformin for 4 days surrounding IV contrast administration to evaluate for contrast-induced
      acute kidney injury. This guideline contributed to the practice of discontinuing metformin
      during hospitalization due to the commonness of radiology studies using IV contrast. There is
      no drug interaction between metformin and contrast media nor is there any effect of metformin
      on renal function. Given the risk of contrast-induced acute kidney injury is very low in
      patients with normal renal function and no co-morbidities, the revised (2013) American
      College of Radiology guidelines recommend that metformin can be continued without the need to
      evaluate renal function following contrast media. In the presence of co-morbidities that
      increase the risk for developing acidosis (liver dysfunction, alcohol abuse, heart failure,
      myocardial or peripheral muscle ischemia, sepsis or severe infection), the new guidelines
      recommend holding metformin for two days after IV contrast administration. Our study will
      only include patients without these co-morbidities and with normal renal function (eGFR > 60
      ml/min). All subjects will have serum creatinine measured daily, and metformin will be
      discontinued in the event of acute kidney injury.

      Since metformin is safe and effective for glucose management in patients with type 2 diabetes
      and normal renal function, we propose its continuation during hospitalization. This study
      will include adult patients with type 2 diabetes currently treated with metformin alone or in
      combination with other anti-diabetic agents including low dose insulin. All subjects will
      have normal renal function (eGFR>60 ml/min) and no comorbidities that increase the risk for
      acidosis. This prospective, randomized controlled trial will compare metformin and
      sitagliptin (which cannot cause hypoglycemia) to usual insulin therapy, which is known to
      cause hypoglycemia. This study has possible implications for improving the safety of therapy
      for hospitalized patients with type 2 diabetes.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: mean blood glucose for the duration of the hospital stay
time frame: duration of hospital stay
description: Participants will be followed for the duration of the hospital stay, an expected average of 5 days.
measure: frequency of hypoglycemia
time frame: duration of hospital stay
description: Participants will be followed for the duration of the hospital stay, an expected average of 5 days. The outcome is the percent of patients having any blood glucose value less than 70 mg/dl during their hospital stay.
measure: Acute kidney injury
time frame: duration of hospital stay
description: Participants will be followed for the duration of the hospital stay, an expected average of 5 days. The outcome is the percent of patients who develop acute kidney injury during their hospital stay. Acute kidney injury is defined as an absolute increase in the serum creatinine concentration of ≥ 0.3 mg/dL from baseline or a percentage increase in the serum creatinine concentration of ≥ 50%
arm group label: insulin glargine and insulin lispro
arm group type: Active Comparator
description: insulin glargine 0.3 units per kg and insulin lispro 0.1 units per kg with each meal
arm group label: metformin and sitagliptin
arm group type: Experimental
description: metformin 750 mg PO twice daily and sitagliptin 100 mg PO once daily
intervention type: Drug
intervention name: metformin and sitagliptin
description: metformin 750 mg PO twice daily
arm group label: metformin and sitagliptin
other name: glucophage
intervention type: Drug
intervention name: insulin glargine and insulin lispro
description: insulin glargine given once daily
arm group label: insulin glargine and insulin lispro
other name: lantus insulin
intervention type: Drug
intervention name: metformin and sitagliptin
description: sitagliptin 100 mg PO once daily
arm group label: metformin and sitagliptin
other name: Januvia
intervention type: Drug
intervention name: insulin glargine and insulin lispro
description: insulin lispro given three times daily with meals
arm group label: insulin glargine and insulin lispro
other name: humalog insulin
criteria: 
gender: All
minimum age: 18 Years
maximum age: 80 Years
healthy volunteers: No
responsible party type: Sponsor
mesh term: Diabetes Mellitus
mesh term: Diabetes Mellitus, Type 2
mesh term: Insulin
mesh term: Insulin, Globin Zinc
mesh term: Metformin
mesh term: Insulin Glargine
mesh term: Sitagliptin Phosphate
mesh term: Insulin Lispro