Sitagliptin Prophylaxis for Glucocorticoid-Induced Impairment of Glucose Metabolism in Males With the Metabolic Syndrome
Condition: Diabetes Mellitus; Steroid Diabetes; Glucocorticoid-induced Diabetes; Beta-cell Function
MeSH terms: Diabetes Mellitus; Metabolic Syndrome
Study type: Interventional

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.
    

Intervention name(s): Sitagliptin 100 mg; Prednisolone 30 mg; Sitagliptin-placebo; Prednisolone-placebo
Intervention type(s): Drug; Drug; Drug; Drug
Intervention description(s): 28 days administration of 100 mg daily; 14 days administration of 30 mg daily; 28 days administration once daily; 14 days administration once daily
Other intervention name(s): Januvia; MK-0431; ATC A10BH01; prednison; ATC H02AB06
Intervention MeSH terms: Sitagliptin Phosphate; Prednisolone; Methylprednisolone Acetate; Methylprednisolone; Methylprednisolone Hemisuccinate; Prednisolone acetate; Prednisolone hemisuccinate; Prednisolone phosphate
Allocation: Randomized
Intervention model: Factorial Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Primary purpose: Prevention
Keywords: beta-cell function; glucocorticoid-induced diabetes; glucocorticoid; DPP-4 inhibitors; sitagliptin; diabetes mellitus; steroid diabetes; insulin resistance; insulin sensitivity