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

April 30, 2013
July 2, 2014
July 2013
December 2015   (final data collection date for primary outcome measure)
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
Same as current
Complete list of historical versions of study NCT01845831 on ClinicalTrials.gov Archive Site
  • 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.
Same as current
Not Provided
Not Provided
 
Sitagliptin Therapy in Hospitalized Patients With Type 2 Diabetes
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

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

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.

Interventional
Phase 4
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Type 2 Diabetes
  • Drug: Sitagliptin + glargine
    Sitagliptin and Glargine once daily + correction doses of rapid acting insulin if needed
    Other Name: Januvia and Lantus
  • 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)
  • 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
  • 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
  • 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
  • Experimental: Sitagliptin + glargine (Hospital)
    Sitagliptin and glargine once daily + correction doses of aspart or lispro if needed
    Intervention: Drug: Sitagliptin + glargine
  • Active Comparator: Basal bolus (Hospital)
    Glargine once daily and rapid-acting insulin before meals + correction doses of aspart or lispro if needed
    Intervention: Drug: Basal Bolus
  • 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
    Intervention: Drug: Metformin and sitagliptin
  • 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
    Intervention: Drug: Metformin and sitagliptin + glargine 50%
  • 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
    Intervention: Drug: Metformin and sitagliptin + glargine 80%
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
280
December 2016
December 2015   (final data collection date for primary outcome measure)

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.
Both
18 Years to 80 Years
No
Contact: Guillermo E Umpierrez, MD 404-778-1665 geumpie@emory.edu
Contact: Francisco J Pasquel, MD 404-778-1688 fpasque@emory.edu
United States
 
NCT01845831
IRB00063642
Yes
Guillermo Umpierrez, Emory University
Emory University
Not Provided
Principal Investigator: Guillermo Umpierrez, MD Emory University SOM
Emory University
July 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP