Sitagliptin Therapy in Hospitalized Patients With Type 2 Diabetes

Type 2 Diabetes Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01845831
• Other study ID #: IRB00063642
• Status: Completed
• Phase: Phase 4
• First received: April 30, 2013
• Last updated: April 12, 2016
• Start date: August 2013
• Est. completion date: April 2016

Study information

• Verified date: April 2016
• Source: Emory University
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 292
• Est. completion date: April 2016
• Est. primary completion date: April 2016
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 80 Years

Eligibility

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.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 2
• Type 2 Diabetes

Intervention

Drug:
• Sitagliptin + glargine
Sitagliptin and Glargine once daily + correction doses of rapid acting insulin if needed
• 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
• 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
• 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
• 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

Locations

Country	Name	City	State
United States	University of Michigan	Ann Arbor	Michigan
United States	Emory University Hospital	Atlanta	Georgia
United States	Grady Memorial Hospital	Atlanta	Georgia
United States	Ohio State University	Columbus	Ohio
United States	Temple University	Philadelphia	Pennsylvania

Sponsors (5)

Lead Sponsor	Collaborator
Emory University	Merck Sharp & Dohme Corp., Ohio University, Temple University, University of Michigan

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Glycemic control	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	During hospitalization, average 5 days	No
Secondary	Hypoglycemia	Number of hypoglycemic events (<70 mg/dl) and severe hypoglycemic events (<40 mg/dl)	During hospitalization, average 5 days	Yes
Secondary	Hyperglycemia	Number of episodes of hyperglycemia (BG > 300 mg/dl) after the first day of treatment	During hospitalization, average 5 days	Yes
Secondary	Total daily insulin dose	Daily insulin requirement (unit/day) and number of insulin injections	During hospitalization, average 5 days	No
Secondary	Days of hospitalization	Length of hospital stay	During hospitalization, average 5 days	No
Secondary	ICU need	Need for ICU care (transfer to ICU)	During hospitalization, average 5 days	No
Secondary	Composite of hospital complications	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)	During hospitalization, average 5 days	No
Secondary	Acute Renal Failure	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).	During hospitalization, average 5 days	No
Secondary	Hospital mortality	Hospital mortality. Mortality is defined as death occurring during admission.	During hospitalization, average 5 days	No