Effects of an 11β-hydroxysteroid dehydrogenase type 1 inhibitor, MK-0916, in patients with type 2 diabetes mellitus and metabolic syndrome
Version of Record online: 20 APR 2011
© 2011 Blackwell Publishing Ltd
Diabetes, Obesity and Metabolism
Volume 13, Issue 6, pages 498–504, June 2011
How to Cite
Feig, P. U., Shah, S., Hermanowski-Vosatka, A., Plotkin, D., Springer, M. S., Donahue, S., Thach, C., Klein, E. J., Lai, E. and Kaufman, K. D. (2011), Effects of an 11β-hydroxysteroid dehydrogenase type 1 inhibitor, MK-0916, in patients with type 2 diabetes mellitus and metabolic syndrome. Diabetes, Obesity and Metabolism, 13: 498–504. doi: 10.1111/j.1463-1326.2011.01375.x
- Issue online: 20 APR 2011
- Version of Record online: 20 APR 2011
- Accepted manuscript online: 28 JAN 2011 05:12AM EST
- Date submitted 21 September 2010; date of first decision 4 November 2010; date of final acceptance 24 December 2010
- 11β-hydroxysteroid dehydrogenase type 1 inhibitor;
- metabolic syndrome;
- type 2 diabetes mellitus
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 A1c (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.