Sitagliptin Therapy in Hospitalized Patients With Type 2 Diabetes

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2014 by Emory University
Sponsor:
Information provided by (Responsible Party):
Guillermo Umpierrez, Emory University
ClinicalTrials.gov Identifier:
NCT01845831
First received: April 30, 2013
Last updated: July 2, 2014
Last verified: July 2014
  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 Florida Hospital Diabetes institute


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

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: 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 Emory University:

Primary Outcome Measures:
  • Glycemic control [ Time Frame: During hospitalization, average 5 days ] [ Designated as safety issue: No ]
    The primary outcome of the study is to determine differences in glycemic control as measured by mean daily BG concentration between sitagliptin once daily and basal bolus therapy with glargine once daily plus supplemental lispro insulin in hospitalized patients with T2D


Secondary Outcome Measures:
  • Hypoglycemia [ Time Frame: During hospitalization, average 5 days ] [ Designated as safety issue: Yes ]
    Number of hypoglycemic events (<70 mg/dl) and severe hypoglycemic events (<40 mg/dl)

  • Hyperglycemia [ Time Frame: During hospitalization, average 5 days ] [ Designated as safety issue: Yes ]
    Number of episodes of hyperglycemia (BG > 300 mg/dl) after the first day of treatment

  • Total daily insulin dose [ Time Frame: During hospitalization, average 5 days ] [ Designated as safety issue: No ]
    Daily insulin requirement (unit/day) and number of insulin injections

  • Days of hospitalization [ Time Frame: During hospitalization, average 5 days ] [ Designated as safety issue: No ]
    Length of hospital stay

  • ICU need [ Time Frame: During hospitalization, average 5 days ] [ Designated as safety issue: No ]
    Need for ICU care (transfer to ICU)

  • Composite of hospital complications [ Time Frame: During hospitalization, average 5 days ] [ Designated as safety issue: No ]
    Differences between groups on a composite of hospital complications including pneumonia, wound infections, bacteremia, respiratory failure, acute renal failure, and major cardiovascular events (acute myocardial infarction, congestive heart failure, and cardiac arrhythmias)

  • Acute Renal Failure [ Time Frame: During hospitalization, average 5 days ] [ Designated as safety issue: No ]
    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 [ Time Frame: During hospitalization, average 5 days ] [ Designated as safety issue: No ]
    Hospital mortality. Mortality is defined as death occurring during admission.


Estimated Enrollment: 280
Study Start Date: July 2013
Estimated Study Completion Date: December 2016
Estimated Primary Completion Date: December 2015 (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 + glargine
Sitagliptin and Glargine once daily + correction doses of rapid acting insulin if needed
Other Name: Januvia and 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
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 + 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
Other Name: Janumet, Lantus
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 + 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
Other Name: Janumet, Lantus

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 (≤0.4 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

Ages Eligible for Study:   18 Years to 80 Years
Genders Eligible for Study:   Both
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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01845831

Contacts
Contact: Guillermo E Umpierrez, MD 404-778-1665 geumpie@emory.edu
Contact: Francisco J Pasquel, MD 404-778-1688 fpasque@emory.edu

Locations
United States, Georgia
Grady Memorial Hospital Recruiting
Atlanta, Georgia, United States, 30303
Contact: Guillermo Umpierrez, MD       geumpie@emory.edu   
Contact: Francisco Pasquel, MD    4047781688    fpasque@emory.edu   
Principal Investigator: Guillermo Umpierrez, MD         
Sub-Investigator: Francisco Pasquel, MD         
Sub-Investigator: Dawn Smiley, MD         
Sub-Investigator: Priya Vellanki, MD         
Emory University Hospital Recruiting
Atlanta, Georgia, United States, 30324
Contact: Dawn Smiley, MD       dsmiley@emory.edu   
Sub-Investigator: Dawn Smiley, MD         
United States, Michigan
University of Michigan Recruiting
Ann Arbor, Michigan, United States, 48109
Contact: Roma Gianchandani, MD       romag@med.umich.edu   
Principal Investigator: Roma Gianchandani, MD         
United States, Ohio
Ohio State University Recruiting
Columbus, Ohio, United States, 43210
Contact: Kathleen Dungan, MD       Kathleen.Dungan@osumc.edu   
Principal Investigator: Kathleen Dungan, MD         
United States, Pennsylvania
Temple University Recruiting
Philadelphia, Pennsylvania, United States, 19140
Contact: Daniel Rubin, MD       Daniel.Rubin@tuhs.temple.edu   
Principal Investigator: Daniel Rubin, MD         
Sponsors and Collaborators
Emory University
Investigators
Principal Investigator: Guillermo Umpierrez, MD Emory University SOM
  More Information

No publications provided

Responsible Party: Guillermo Umpierrez, Professor of Medicine, Emory University
ClinicalTrials.gov Identifier: NCT01845831     History of Changes
Other Study ID Numbers: IRB00063642
Study First Received: April 30, 2013
Last Updated: July 2, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by 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
Glargine
Sitagliptin
Metformin
Hypoglycemic Agents
Physiological Effects of Drugs
Pharmacologic Actions
Dipeptidyl-Peptidase IV Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on July 29, 2014