Effects of Sitagliptin (Januvia®) on Blood Glucose Control in Patients With Type 1 Diabetes

Effects of Sitagliptin (Januvia®) on Blood Glucose Control in Patients With Type 1 Diabetes and CGM Substudy of the Investigator Initiated Study Protocol Effects of Sitagliptin (Januvia) on Glucagon Suppression and GLP-1 Levels in Patients With Type 1 Diabetes; CGM Substudy

Sponsors

Lead Sponsor: University of Colorado Denver School of Medicine Barbara Davis Center

Source University of Colorado Denver School of Medicine Barbara Davis Center
Brief Summary

This is a multi-center, prospective, randomized, double-blind, parallel, placebo controlled clinical trial evaluating the efficacy of sitagliptin in suppressing glucagon release in subjects with type 1 diabetes over a 16 week treatment period. The hypothesis of this study is that sitagliptin (Januvia™) will decrease post-prandial glucagon release and may result in improved glucose control in adult patients with type 1 diabetes. There is only one small, pilot study of sitagliptin in patients with type 1 diabetes which significantly reduced total daily insulin dose and A1c values while improving mean blood glucose (MBG) and time spent in euglycemic range (1). In the pilot study, GLP-1 and glucagon levels were not assessed. The purpose of this trial is to determine if sitagliptin can suppress the paradoxical rise of glucagon, and thus can decrease A1c.

This study will enroll a maximum of 140 patients (with an expected 10% dropout rate) with A1c values between 7.5-10% who will be randomized in a 1:1 fashion to either the study drug or placebo. 100 of these patients will wear a continuous glucose monitor. Subjects may be using insulin via continuous subcutaneous insulin infusion (CSII) or multiple daily injections (MDI). The clinic visits will be conducted at screening, -1 week, baseline/randomization, 4 weeks, 12 weeks, and 16 weeks in addition to telephone visits (Appendix 1 and 2). At home, starting at week 0 (randomization/baseline), subjects will take 100 mg/day of sitagliptin or placebo and continue for the study duration. Laboratory analysis will be performed at various time points assessing glucagon, A1c, C-peptide, glucagon-like-peptide-1 (GLP-1), glucose-dependent insulinotropic peptide (GIP), and insulin levels.

Overall Status Completed
Start Date November 2010
Completion Date July 2011
Primary Completion Date July 2011
Phase N/A
Study Type Interventional
Primary Outcome
Measure Time Frame
To demonstrate a decrease in post-prandial glucagon release as assessed by glucagon area under the curve (AUC) for 3 hours during 4 hour meal tolerance tests Primary outcome meausre will be recoreded after 16 weeks of treatment
Secondary Outcome
Measure Time Frame
Secondary objectives: 1. To demonstrate a 0.3% decrease in A1c in patients with type 1 diabetes after 16 weeks of treatment with sitagliptin. 2. To evaluate changes in total, basal and bolus insulin dose while on sitagliptin. Secondary outcome meausre will be recoreded after 16 weeks of treatment
Enrollment 140
Condition
Intervention

Intervention Type: Drug

Intervention Name: Sitagliptin

Description: pill/tablet form of 100mg each. will take one tablet a day throughout study

Arm Group Label: Sitagliptin

Intervention Type: Drug

Intervention Name: Sugar Pill

Description: 100mg tablet once a day

Arm Group Label: Sugar Pill

Eligibility

Criteria:

Inclusion Criteria:

- Signed informed consent before any study-related activities

- Male or female aged 18 to 70 years

- Type 1 diabetes mellitus duration > 1 year

- Treatment with MDI or CSII therapy for at least 3 months prior to screening visit; stable insulin dose for the last 1 month

- No use of pramlintide, saxagliptin, metformin or sitagliptin for 1 month prior to enrollment

- A1c 7.5-10%

- Willingness to routinely practice at least 2-4 blood glucose measurements per day

- BMI ≤ 35 kg/m2

- Ability and willingness to adhere to the protocol including daily oral dose of study drug or placebo and week-long CGM wear

- Willing to complete phone and clinic visits

- Ability to speak, read and write English

Exclusion Criteria:

- Use of oral, inhaled or pre-mixed insulin

- Pregnant or intention to become pregnant during the course of the study not using adequate birth control methods

- Severe unexplained hypoglycemia requiring emergency treatment in the previous 3 months

- Use of systemic or inhaled corticosteroids

- History of hemoglobinopathies

- Diagnosis of anemia

- Post-renal transplantation, currently undergoing dialysis, creatinine >2.0 mg/dl or a calculated creatinine clearance of <50 mL/min

- Advanced retinopathy needing laser procedure or vitrectomy

- History of pancreatitis

- Extensive skin changes/diseases that inhibit wearing a sensor on normal skin

- Known allergy to adhesives

- Known allergy to study medication

- Participation in another investigational study protocol within 30 days prior to enrollment

- Any other condition, as determined by the investigator, which could make the subject unsuitable for the trial, impairs the subject's suitability for the trial, or impairs the validity of the informed consent

Gender: All

Minimum Age: 18 Years

Maximum Age: 70 Years

Healthy Volunteers: No

Overall Official
Last Name Role Affiliation
Satish K Garg, MD Principal Investigator University of Colorado Denver, Barbara Davis Center
Location
Facility: University of Colorado/Barbara Davis Center for Diabetes
Location Countries

United States

Verification Date

May 2014

Responsible Party

Type: Principal Investigator

Investigator Affiliation: University of Colorado Denver School of Medicine Barbara Davis Center

Investigator Full Name: Satish K. Garg

Investigator Title: Professor of Medicine and Pediatrics

Keywords
Has Expanded Access No
Condition Browse
Number Of Arms 2
Arm Group

Label: Sitagliptin

Type: Experimental

Label: Sugar Pill

Type: Placebo Comparator

Study Design Info

Allocation: Randomized

Intervention Model: Parallel Assignment

Primary Purpose: Supportive Care

Masking: Triple (Participant, Care Provider, Investigator)

Source: ClinicalTrials.gov