NCT00721552

Sitagliptin Prophylaxis for Glucocorticoid-Induced Impairment of Glucose Metabolism in Males With the Metabolic Syndrome

Sitagliptin Prophylaxis for Glucocorticoid-Induced Impairment of Glucose Metabolism and Beta-Cell Dysfunction in Males With the Metabolic Syndrome X: A Randomized, Placebo-controlled, Double-blind Intervention Study With a 2x2 Factorial Design

• Status: Completed
• Phase: N/A
• Study type: Interventional
• Enrollment: 82 (actual)
• Sponsor: Amsterdam UMC, location VUmc · Academic / Other
• Sex: Male
• Age: 35 Years – 65 Years
• Healthy volunteers: Accepted

Summary

The investigators will assess whether the DPP-inhibitor sitagliptin will ameliorate glucocorticoid-induced impairment of glucose metabolism and beta-cell dysfunction and thus could be used as a prophylaxis for glucocorticoid-induced diabetes. Therefore the investigators will administer in males with the metabolic syndrome 30 mg prednisolone daily for two weeks and give simultaneously sitagliptin 100 mg daily. Subjects will undergo at baseline and after two weeks of treatment several tests to assess changes in glucose metabolism.

Detailed description

The investigators will conduct a randomized, placebo-controlled, double-blind, 2x2 factorial-designed intervention trial. The pharmacological intervention for prednisolone/prednisolone-placebo is 14 days and for sitagliptin/sitagliptin-placebo 28 days. Subjects fulfilling the IDF criteria26 for the metabolic syndrome (aged 35-65; n=60) will be randomized to one of four groups: I) prednisolone 30 mg and sitagliptin 100 mg daily; II) prednisolone 30 mg and sitagliptin-placebo daily; III) prednisolone-placebo and sitagliptin 100 mg daily; IV) prednisolone-placebo and sitagliptin-placebo daily. Before and at day 14 of treatment subjects will undergo a standardized mixed-meal test in order to assess glucose disposal and beta-cell function (by modeling analysis). During these meal tests, plasma concentrations of (total and active) GLP-1, GIP, glucagon and additional biomarkers will be assessed. A combined hyperglycemic-euglycemic clamp will be performed at baseline and at day 13 of treatment to assess insulin sensitivity and insulin secretion. During the euglycemic clamp adipose tissue and muscle biopsies will be obtained, both in fasting and under hyperinsulinemic conditions. At baseline and at day 28 of treatment, a 7-point OGTT will be performed to assess time to restoration of glycemic control. Body composition, body fat distribution and liver fat content, measured by respectively bio-impedance analysis and magnetic resonance imaging/spectroscopy (MRI/MRS), will be assessed at baseline and after 28 days of treatment. Blood pressure will be assessed at baseline and after two weeks of treatment. Microvascular function will be assessed with capillary videomicroscopy both at baseline and after two weeks of treatment.

Conditions

• Diabetes Mellitus
• Steroid Diabetes
• Glucocorticoid-induced Diabetes
• Beta-cell Function

Interventions

Type	Name	Description
DRUG	Sitagliptin 100 mg	28 days administration of 100 mg daily
DRUG	Prednisolone 30 mg	14 days administration of 30 mg daily
DRUG	Sitagliptin-placebo	28 days administration once daily
DRUG	Prednisolone-placebo	14 days administration once daily

Timeline

• Start date: 2008-10-01
• Primary completion: 2012-06-01
• Completion: 2012-06-01
• First posted: 2008-07-24
• Last updated: 2012-07-02

Locations

1 site across 1 country: Netherlands