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

University of Vermont

Status: Completed

Conditions: Impaired Glucose Tolerance; Pre-diabetes; Impaired Fasting Glucose

Treatments: Drug: Dexamethasone 2.5 mg and placebo tablet; Drug: Dexamethasone 2.5 mg and Sitagliptin 100 mg

Study type: Interventional

Funder types: Other

Identifiers

NCT01488279

MISP 39681

Details and patient eligibility

About

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

Full 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.

Enrollment: 10 patients

Sex: All

Ages: 18 to 65 years old

Volunteers: Accepts Healthy Volunteers

Inclusion criteria

• Men and women
• impaired fasting glucose
• We will stratify for weight and age.

Exclusion criteria

• Known Type 2 DM
• Severe disease preventing participation in study
• On chronic steroids for any reason
• Already taking DPP-4 inhibitor

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Double Blind

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10 participants in 2 patient groups, including a placebo group

Dexamethasone 2.5mg and Sitagliptin100mg

Active Comparator group

Description:

Participants received Dexamethasone 2.5 mg plus Sitagliptin 100 mg daily for 8 days

Treatment:

Drug: Dexamethasone 2.5 mg and Sitagliptin 100 mg

Drug: Dexamethasone 2.5 mg and placebo tablet

Dexamethasone 2.5mg and placebo tablet

Placebo Comparator group

Description:

Participants received Dexamethasone 2.5 mg plus Sitagliptin-matched placebo tablet daily for 8 days.

Treatment:

Drug: Dexamethasone 2.5 mg and Sitagliptin 100 mg

Drug: Dexamethasone 2.5 mg and placebo tablet