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.