Effects of an 11β-hydroxysteroid dehydrogenase type 1 inhibitor, MK-0916, in patients with type 2 diabetes mellitus and metabolic syndrome

Diabetes Obes Metab. 2011 Jun;13(6):498-504. doi: 10.1111/j.1463-1326.2011.01375.x.

Abstract

Aim: We examined the effects of the 11β-hydroxysteroid dehydrogenase type 1 (HSD1) inhibitor, MK-0916, on the multiple components of the metabolic syndrome (MetS) in patients with type 2 diabetes (T2DM) and MetS.

Methods: This was a 12-week, multicentre, randomized, double-blind, placebo-controlled study. Patients with T2DM (mean baseline A1C: 7.3%) and National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III)-defined MetS were randomized 1 : 1 : 1 : 1 to 0.5, 2 or 6 mg/day MK-0916 or placebo. The primary efficacy endpoint was a change from baseline at week 12 in fasting plasma glucose (FPG). Secondary endpoints included glycosylated haemoglobin A(1c) (A1C), 2-h postprandial glucose (2-h PPG), body weight, waist circumference, blood pressure and lipid profile.

Results: Treatment with MK-0916 had no significant effect relative to placebo on FPG at week 12. Compared to placebo, 6 mg MK-0916 produced a modest, significant (p = 0.049) reduction in A1C of 0.3% at week 12, but no significant difference was observed in 2-h PPG. Six milligram MK-0916 increased LDL-C relative to placebo by 10.4% (p = 0.041). Treatment with MK-0916 led to modest dose-dependent decreases in blood pressure and body weight. Overall, MK-0916 was generally well tolerated. MK-0916 produced mechanism-based activation of the hypothalamic-pituitary-adrenal axis, resulting in mean increases in adrenal androgen levels that remained within the normal range at all doses tested.

Conclusions: Inhibition of HSD1 with MK-0916 was generally well tolerated in patients with T2DM and MetS. Although no significant improvement in FPG was observed with MK-0916 compared to placebo, modest improvements in A1C, body weight and blood pressure were observed.

Publication types

  • Clinical Trial, Phase II
  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • 11-beta-Hydroxysteroid Dehydrogenase Type 1 / antagonists & inhibitors*
  • 11-beta-Hydroxysteroid Dehydrogenase Type 1 / pharmacology*
  • Adolescent
  • Adult
  • Aged
  • Analysis of Variance
  • Blood Glucose / drug effects*
  • Blood Glucose / metabolism
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Diabetes Mellitus, Type 2 / metabolism
  • Diabetes Mellitus, Type 2 / physiopathology
  • Female
  • Glycated Hemoglobin / drug effects*
  • Glycated Hemoglobin / metabolism
  • Humans
  • Male
  • Metabolic Syndrome / drug therapy*
  • Metabolic Syndrome / metabolism
  • Metabolic Syndrome / physiopathology
  • Middle Aged
  • Placebos
  • Postprandial Period
  • Young Adult

Substances

  • Blood Glucose
  • Glycated Hemoglobin A
  • Placebos
  • 11-beta-Hydroxysteroid Dehydrogenase Type 1