NCT01488279

Effect of Sitagliptin on Short-Term Metabolic Dysregulation of Oral Glucocorticoid Therapy

• Status: Completed
• Phase: N/A
• Study type: Interventional
• Enrollment: 10 (actual)
• Sponsor: University of Vermont · Academic / Other
• Sex: All
• Age: 18 Years – 65 Years
• Healthy volunteers: Accepted

Summary

The investigators hypothesize that sitagliptin will significantly reduce impairments in insulin secretion and insulin resistance resulting from short-term oral glucocorticoid therapy.

Detailed description

The investigators plan to conduct a prospective, randomized, double-blind, placebo-controlled parallel arm crossover study comparing insulin secretion and insulin resistance in subjects with impaired fasting glucose on oral glucocorticoid therapy + placebo versus subjects on oral glucocorticoid therapy + sitagliptin. For the oral glucocorticoid therapy, we plan to use dexamethasone (dex) 2.5 mg daily. We chose dex for known glycemic effects, improved compliance, and once daily dosing. Previous studies have shown that in humans, glucocorticoid-induced insulin resistance develops within 4 hours with infused drug at high dose (methylprednisolone 500 mg x single infusion) and does not change with duration of drug therapy of up to 3 months.10 Furthermore, more modest doses over a short duration (dex 2.0 mg orally daily x 2 days) have been shown to decrease insulin-mediated glucose disposal.11 12 Thus, studying acute effects of oral dex at 2.5 mg daily x 7 days should be more than adequate to achieve impaired glucose-mediated insulin secretion and impaired insulin-mediated glucose disposal. In order for sitagliptin to have the desired effect, drug should be administered for at least 7 days (5 half-lives plus 40% more for margin of error). We plan to study subjects with impaired fasting glucose or impaired glucose tolerance as they would likely be candidates for DPP-IV therapy in the future and would be likely to have impaired insulin secretion and impaired glucose disposal amenable to DPP-IV therapy. A total of 10 participants were enrolled in this study. Participants were given 2.5 mg dexamethasone daily plus either placebo tablet or sitagliptin daily for 8 days with a washout period prior to crossover. The order of study drug administration was randomized. Participants underwent blood sampling, mixed meal testing (MMT), and intravenous glucose tolerance testing (IVGTT) before and after each study period.

Conditions

• Pre-diabetes
• Impaired Fasting Glucose
• Impaired Glucose Tolerance

Interventions

Type	Name	Description
DRUG	Dexamethasone 2.5 mg and Sitagliptin 100 mg	Participants received Dexamethasone 2.5mg plus Sitaliptin 100mg daily for 8 days
DRUG	Dexamethasone 2.5 mg and placebo tablet	Participants rececived Dexamethasone 2.5 mg plus placebo tablet daily for 8 days

Timeline

• Start date: 2012-09-01
• Primary completion: 2014-07-01
• Completion: 2015-12-01
• First posted: 2011-12-08
• Last updated: 2018-03-12
• Results posted: 2018-02-09

Locations

1 site across 1 country: United States