Clinical trial NCT01378117: Dipeptidyl Peptidase-4 Inhibitor (Sitagliptin) Therapy in the Inpatients With Type 2 Diabetes
Official title: Randomized Controlled Study of Dipeptidyl Peptidase-4 (DPP4) Inhibitor (Sitagliptin) Therapy in the Inpatient Management of Patients With Type 2 Diabetes
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Type 2 Diabetes Mellitus
Hospitalization
Hyperglycemia
Keywords: diabetes
non critical care setting
hyperglycemia
treatment
oral antidiabetic agents
subcutaneous insulin
Lead sponsor: Emory University
Sponsor class: OTHER
Collaborators: name: Merck Sharp & Dohme LLC
First posted: 2011-06-22
Enrollment: 90
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The study is a multicenter, prospective, open-label, randomized pilot study to investigate the safety and efficacy of sitagliptin (Januvia) for the inpatient management of type 2 diabetes (T2D) in general medicine and surgery patients.

Detailed description: 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, but has not been tested in the hospital. It is not known if sitagliptin is as effective in controlling blood sugars in the hospital. This study will compare sitagliptin by mouth, insulin (glargine) injection, and the combination of sitagliptin and lantus insulin in controlling blood sugar in hospitalized patients with diabetes.

In this pilot study, patients with known history of diabetes treated with diet and/or oral anti-diabetics or with low total daily dose insulin therapy (\<0.4 unit/kg/day) will be randomized to receive sitagliptin once daily (group 1), sitagliptin plus basal (glargine) insulin once daily (group 2), or basal bolus regimen with glargine once daily and lispro insulin before meals (group 3). If needed, patients in the 3 treatment groups will receive correction doses of rapid-acting lispro (Humalog®) insulin in the presence of hyperglycemia (BG \> 140 mg/dl) per sliding scale. The overall hypothesis is that treatment with sitagliptin once daily alone or in combination with basal insulin in patients with type 2 diabetes will result in a similar improvement in 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.

A total of 90 subjects with type 2 diabetes will be recruited in this study. Patients will be recruited at Grady Memorial Hospital and Emory University Hospital.

Eligibility criteria: Inclusion Criteria:

1. Males or females between the ages of 18 and 80 years admitted to a general medicine and surgery services.
2. A known history of type 2 diabetes mellitus \> 3 months, receiving either diet alone, oral antidiabetic agents: sulfonylureas and metformin as monotherapy or in combination therapy (excluding Trazodone (TZDs) and DPP4 inhibitors), or low-dose (≤ 0.4 units/kg/day) insulin therapy.
3. Subjects with a BG \>140 mg and \< 400 mg/dL without laboratory evidence of diabetic ketoacidosis (serum bicarbonate \< 18 milliequivalent /L or positive serum or urinary ketones).

Exclusion Criteria:

1. Age \< 18 or \> 80 years.
2. Subjects with increased blood glucose concentration, but without a known 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. History of TZD treatment (pioglitazone or rosiglitazone) or DPP4 inhibitor (sitagliptin or saxagliptin) during the past 3 months prior to admission.
5. Acute critical illness or coronary artery bypass graft (CABG) surgery expected to require prolonged admission to a critical care unit (ICU, cardiac care unit , surgical intensive care unit, neuro ICU).
6. Subjects with gastrointestinal obstruction or adynamic ileus or those expected to require gastrointestinal suction.
7. Medical or surgical patients expected to be kept nil per os (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 congestive heart failure (NYHA class III and IV), acute myocardial infarction, clinically significant hepatic disease or significantly impaired renal function (serum creatinine ≥ 2.0 mg/dL).
10. Treatment with oral or injectable corticosteroid.
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.

Primary outcomes:
measure: Mean Blood Glucose Levels Among the Three Groups at the Time of Hospitalization to 1st Day After Therapy
timeFrame: Admission and after 1st day of therapy
Secondary outcomes:
measure: Number of Patients With Hypoglycemic Events Among the Treatment Groups
timeFrame: during hospitalization,up to 10 days
measure: Number of Patients With Severe Hypoglycemic Episodes Among the 3 Treatment Groups
timeFrame: during hospitalization,up to 5 days
measure: Number of Patients With a Mean Daily BG > 240 mg/dL After the 1st Day of Treatment Among the Treatment Groups
timeFrame: during hospitalization,up to 10 days
measure: Mean Total Daily Dose of Insulin in Units/Day Given During Hospitalization Among the Three Groups
timeFrame: during hospitalization, up to 10 days
measure: Mean Length of Stay in Days in the Hospital Among Different Groups
timeFrame: during hospitalization, up to 10 days
measure: Number of Subjects With Acute Renal Failure Among the Three Randomized Groups During Hospitalization
timeFrame: during hospitalization, up to 10 days
measure: Number of Deaths Among the Subjects in Different Groups
timeFrame: during hospitalization, up to 10 days
measure: Percent of Blood Glucose Readings Within Target Range Between 70 and 140 mg/dL Among the Three Groups After 24 Hrs of Randomized Treatment
timeFrame: during hospitalization, up to 10 days
Other outcomes:
Locations:
city: Atlanta
country: United States
facility: Grady Memorial Hospital
state: Georgia
city: Atlanta
country: United States
facility: Emory University Hospital
state: Georgia
Study officials:
affiliation: Emory University SOM
name: Guillermo Umpierrez, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Umpierrez GE, Gianchandani R, Smiley D, Jacobs S, Wesorick DH, Newton C, Farrokhi F, Peng L, Reyes D, Lathkar-Pradhan S, Pasquel F. Safety and efficacy of sitagliptin therapy for the inpatient management of general medicine and surgery patients with type 2 diabetes: a pilot, randomized, controlled study. Diabetes Care. 2013 Nov;36(11):3430-5. doi: 10.2337/dc13-0277. Epub 2013 Jul 22.