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Sitagliptin Therapy in Hospitalized Patients With Type 2 Diabetes

This study has been completed.
Sponsor:
ClinicalTrials.gov Identifier:
NCT01845831
First Posted: May 3, 2013
Last Update Posted: May 30, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Collaborators:
Merck Sharp & Dohme Corp.
Temple University
University of Michigan
Ohio University
Information provided by (Responsible Party):
Guillermo Umpierrez, Emory University
  Purpose

High blood glucose levels in hospitalized patients with diabetes are associated with increased risk of medical complications and death. Improved glucose control with insulin injections may improve clinical outcome and prevent some of the hospital complications. Glargine (Lantus®) insulin injection is the most common treatment of diabetes in the hospital. Sitagliptin (Januvia®)is effective in lowering blood glucose. In a recent pilot study aiming to determine differences in glycemic control between treatment with sitagliptin (Januvia®) alone or in combination with basal insulin and basal bolus regimen in general medicine and surgery patients with type 2 diabetes (T2D). The investigators found that treatment with sitagliptin alone or in combination with basal insulin resulted in similar glycemic control compared to basal bolus regimen.

The investigators will conduct a prospective RCT aimed to determine the safety and efficacy of sitagliptin therapy for in-hospital and post-discharge management of general medicine and surgical patients with T2D. A total of 280 patients with known history of diabetes will be randomized to receive sitagliptin plus basal (glargine) insulin once daily (group 1), or basal bolus regimen with glargine once daily and aspart or lispro insulin before meals (group 2). If needed, patients in the treatment groups will receive correction doses of rapid-acting insulin in the presence of hyperglycemia (BG > 140 mg/dl). The overall hypothesis is that treatment with sitagliptin in combination with basal insulin in patients with type 2 diabetes will result in a similar improvement in hospital and post-discharge glycemic control and in a lower frequency of hypoglycemic events than treatment with basal bolus insulin regimen with glargine once daily and lispro insulin before meals.

Patients will be recruited at Grady Memorial Hospital, Emory University Hospital, University of Michigan, Ohio State University and Temple University


Condition Intervention Phase
Type 2 Diabetes Drug: Sitagliptin Drug: Basal Bolus Drug: Metformin and Sitagliptin Drug: Glargine Drug: Glargine 50% Drug: Glargine 80% Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Randomized Controlled Trial on the Safety and Efficacy of Sitagliptin Therapy for the Inpatient Management of General Medicine and Surgery Patients With Type 2 Diabetes

Resource links provided by NLM:


Further study details as provided by Guillermo Umpierrez, Emory University:

Primary Outcome Measures:
  • Mean Blood Glucose Concentration After First Day of Treatment [ Time Frame: Duration of Hospitalization (Up to 10 Days) ]
    The average blood glucose (BG) concentration after the first day of treatment

  • Mean Percentage of Blood Glucose Readings Between 3.9 - 7.8 mmol/L [ Time Frame: Duration of Hospitalization (Up to 10 Days) ]
    Differences in glycemic control as measured by mean daily blood glucose (BG) concentration between sitagliptin once daily and basal bolus therapy with glargine once daily plus supplemental lispro insulin in hospitalized patients with T2D.

  • Mean Percentage of Blood Glucose Readings Between 3.9 - 10.0 mmol/L [ Time Frame: Duration of Hospitalization (Up to 10 Days) ]
    Differences in glycemic control as measured by mean daily blood glucose (BG) concentration between sitagliptin once daily and basal bolus therapy with glargine once daily plus supplemental lispro insulin in hospitalized patients with T2D.

  • Mean Percentage of Blood Glucose Readings Between 5.6 - 7.8 mmol/L [ Time Frame: Duration of Hospitalization (Up to 10 Days) ]
    Differences in glycemic control as measured by mean daily blood glucose (BG) concentration between sitagliptin once daily and basal bolus therapy with glargine once daily plus supplemental lispro insulin in hospitalized patients with T2D.

  • Mean Percentage of Blood Glucose Readings Greater Than 13.3 mmol/L [ Time Frame: Duration of Hospitalization (Up to 10 Days) ]
    Differences in glycemic control as measured by mean daily blood glucose (BG) concentration between sitagliptin once daily and basal bolus therapy with glargine once daily plus supplemental lispro insulin in hospitalized patients with T2D.

  • Change in HbA1C [ Time Frame: Post Hospital Discharge Month 3, Month 6 ]
    The mean HbA1C measured at 3 months and 6 months post hospitalization. HbA1C is an indicator of diabetes control; below 6.0% is normal, 6.0% to 6.4% indicates prediabetes, and 6.5% or over indicates diabetes.


Secondary Outcome Measures:
  • Number of Participants With a Hypoglycemic Event [ Time Frame: Duration of Hospitalization (Up to 10 Days) ]
    The number of participants who had a hypoglycemic event during hospitalization.

  • Total Daily Insulin Dose [ Time Frame: Duration of Hospitalization (Up to 10 Days) ]
    Daily insulin requirement (units per day).

  • Length of Hospital Stay [ Time Frame: Duration of Hospitalization (Up to 10 Days) ]
    Length of hospital stay in days.

  • Acute Renal Failure Rate [ Time Frame: Duration of Hospitalization (Up to 10 Days) ]
    Acute renal failure is defined as a clinical diagnosis of acute renal failure with documented new-onset abnormal renal function (increment > 0.5 mg/dL from baseline).

  • Hospital Mortality Rate [ Time Frame: Duration of Hospitalization (Up to 10 Days) ]
    Mortality is defined as death occurring during admission.


Enrollment: 292
Study Start Date: August 2013
Study Completion Date: April 2016
Primary Completion Date: April 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Sitagliptin + glargine (Hospital)
Sitagliptin and glargine once daily + correction doses of aspart or lispro if needed
Drug: Sitagliptin
Sitagliptin will be taken orally at 100 mg or 50 mg once a day per renal function.
Other Name: Januvia
Drug: Glargine

Patients with blood glucose between 140-200 mg/dL during hospitalization will receive 0.2 units per kg weight per day.

Patients with blood glucose between 201-400 mg/dL during hospitalization will receive 0.25 units per kg weight per day.

Other Name: Lantus
Active Comparator: Basal bolus (Hospital)
Glargine once daily and rapid-acting insulin before meals + correction doses of aspart or lispro if needed
Drug: Basal Bolus
Basal bolus regimen with glargine once daily and rapid-acting insulin (lispro or aspart) before meals + + correction doses of rapid acting insulin if needed
Other Name: Glargine (Lantus) + aspart (Novolog) or lispro (Humalog)
Experimental: Metformin and Sitagliptin
Patients with HbA1c ≤ 7% will be discharged on the combination of metformin and sitagliptin (Janumet ® 500/50 mg) twice daily for 6 months
Drug: Metformin and Sitagliptin
Janumet is a combination of metformin and sitagliptin. Patients with HbA1c ≤ 7% will be discharged on the combination of metformin and sitagliptin (Janumet ® 500/50 mg) twice daily for 6 months.
Other Name: Janumet
Experimental: Metformin and sitagliptin + glargine 50%
Patients with HbA1c between 7% and 9% will be discharged on metformin and sitagliptin (Janumet ® 500/50 mg) twice daily plus glargine insulin (50% of the inpatient glargine dose) for 6 months
Drug: Metformin and Sitagliptin
Janumet is a combination of metformin and sitagliptin. Patients with HbA1c ≤ 7% will be discharged on the combination of metformin and sitagliptin (Janumet ® 500/50 mg) twice daily for 6 months.
Other Name: Janumet
Drug: Glargine 50%
Glargine will be prescribed at 50% of daily hospital dose.
Experimental: Metformin and sitagliptin + glargine 80%
Patients with HbA1c > 9% will be discharged on metformin and sitagliptin (Janumet ® 500/50 mg) twice daily plus glargine insulin (80% of the inpatient glargine dose) for 6 months
Drug: Metformin and Sitagliptin
Janumet is a combination of metformin and sitagliptin. Patients with HbA1c ≤ 7% will be discharged on the combination of metformin and sitagliptin (Janumet ® 500/50 mg) twice daily for 6 months.
Other Name: Janumet
Drug: Glargine 80%
Glargine will be prescribed at 80% of daily hospital dose.

Detailed Description:

Specific Aim 1: To determine whether in-hospital glycemic control, as measured by mean daily blood glucose concentration and frequency of hypoglycemic events, is different between treatment with sitagliptin (Januvia®) in combination with basal insulin (glargine) and basal bolus regimen (glargine and rapid-acting insulin analog) in general medicine and surgery patients with T2D. Patients with T2D treated with diet and/or OAD or with low total daily dose insulin therapy (≤0.6 unit/kg/day) will be randomized to receive sitagliptin plus glargine insulin (group 1) or basal bolus regimen with glargine once daily and rapid-acting insulin (lispro or aspart) before meals (group 2). If needed, patients in the 2 treatment groups will receive supplemental (correction) doses of rapid-acting insulin before meals for BG > 140 mg/dl.

Specific Aim 2: To determine the efficacy and safety of an A1C based discharge algorithm in controlling BG after discharge in patients with T2D. Patients who participate in the in-hospital (Aim 1) arm will be invited to enroll in this open label prospective outpatient study. The total duration of the study is 6 months. Patients with HbA1c ≤ 7% will be discharged on the combination of metformin and sitagliptin (Janumet ®) twice daily. Those with HbA1c between 7% and 9% will be discharged on metformin and sitagliptin (Janumet ®) twice daily plus glargine insulin at 50% of the inpatient glargine dose. Those with HbA1c > 9% will be discharged on metformin and sitagliptin (Janumet ®) twice-daily plus glargine insulin at 80% of the inpatient dose.

  Eligibility

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 80 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Males or females between the ages of 18 and 80 years admitted to medicine and surgery services.
  2. A known history of Type 2 Diabetes > 1 month, receiving either diet alone, oral antidiabetic agents: sulfonylureas and metformin as monotherapy or in combination therapy (excluding DPP-4 inhibitors) or low-dose (≤ 0.6 units/kg/day) insulin therapy.
  3. Subjects with a blood glucose >140 mg and < 400 mg/dL at time of randomization without laboratory evidence of diabetic ketoacidosis (serum bicarbonate < 18 mEq/L or positive serum or urinary ketones).

Exclusion Criteria:

  1. Age < 18 or > 80 years.
  2. Subjects with increased BG concentration, but without a history of diabetes (stress hyperglycemia).
  3. Subjects with a history of type 1 diabetes (suggested by BMI < 25 requiring insulin therapy or with a history of diabetic ketoacidosis and hyperosmolar hyperglycemic state, or ketonuria) [46].
  4. Treatment with DPP4 inhibitor or Glucagon like peptide 1 (GLP1) analogs during the past 3 months prior to admission.
  5. Acute critical illness or coronary artery bypass graft (CABG) surgery expected to require admission to a critical care unit.
  6. Subjects with gastrointestinal obstruction or adynamic ileus or those expected to require gastrointestinal suction.
  7. Medical or surgical patients expected to be kept NPO for >24-48 hours after admission or after completion of surgical procedure.
  8. Patients with clinically relevant pancreatic or gallbladder disease.
  9. Patients with acute myocardial infarction, clinically significant hepatic disease or significantly impaired renal function (GFR < 30 ml/min).
  10. Treatment with oral or injectable corticosteroid = or > prednisone 5 mg/per day.
  11. Mental condition rendering the subject unable to understand the nature, scope, and possible consequences of the study.
  12. Female subjects are pregnant or breast feeding at time of enrollment into the study.
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01845831


Locations
United States, Georgia
Grady Memorial Hospital
Atlanta, Georgia, United States, 30303
Emory University Hospital
Atlanta, Georgia, United States, 30324
United States, Michigan
University of Michigan
Ann Arbor, Michigan, United States, 48109
United States, Ohio
Ohio State University
Columbus, Ohio, United States, 43210
United States, Pennsylvania
Temple University
Philadelphia, Pennsylvania, United States, 19140
Sponsors and Collaborators
Emory University
Merck Sharp & Dohme Corp.
Temple University
University of Michigan
Ohio University
Investigators
Principal Investigator: Guillermo Umpierrez, MD Emory University SOM
  More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Guillermo Umpierrez, Professor of Medicine, Emory University
ClinicalTrials.gov Identifier: NCT01845831     History of Changes
Other Study ID Numbers: IRB00063642
First Submitted: April 30, 2013
First Posted: May 3, 2013
Results First Submitted: March 8, 2017
Results First Posted: May 30, 2017
Last Update Posted: May 30, 2017
Last Verified: April 2017

Keywords provided by Guillermo Umpierrez, Emory University:
Diabetes
DPP4 inhibitors
Sitagliptin
Glargine
RCT
basal insulin
hospital hyperglycemia
inpatient diabetes

Additional relevant MeSH terms:
Diabetes Mellitus
Diabetes Mellitus, Type 2
Glucose Metabolism Disorders
Metabolic Diseases
Endocrine System Diseases
Insulin, Globin Zinc
Insulin
Metformin
Sitagliptin Phosphate
Insulin Glargine
Insulin Aspart
Insulin Lispro
Insulin, Short-Acting
Hypoglycemic Agents
Physiological Effects of Drugs
Incretins
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Dipeptidyl-Peptidase IV Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action