title: Effects of an 11β-hydroxysteroid dehydrogenase type 1 inhibitor, MK-0916, in patients with type 2 diabetes mellitus and metabolic syndrome.
abstract: OBJECTIVE
  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.
authors.affiliation: Merck Sharp & Dohme Corp., Rahway, NJ, USA. peter_feig@merck.com
authors.forename: P U
authors.initials: PU
authors.lastname: Feig
authors.forename: S
authors.initials: S
authors.lastname: Shah
authors.forename: A
authors.initials: A
authors.lastname: Hermanowski-Vosatka
authors.forename: D
authors.initials: D
authors.lastname: Plotkin
authors.forename: M S
authors.initials: MS
authors.lastname: Springer
authors.forename: S
authors.initials: S
authors.lastname: Donahue
authors.forename: C
authors.initials: C
authors.lastname: Thach
authors.forename: E J
authors.initials: EJ
authors.lastname: Klein
authors.forename: E
authors.initials: E
authors.lastname: Lai
authors.forename: K D
authors.initials: KD
authors.lastname: Kaufman
mesh_terms: D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1 / Q000037:antagonists & inhibitors* / Q000494:pharmacology*; D000293:Adolescent; D000328:Adult; D000368:Aged; D000704:Analysis of Variance; D001786:Blood Glucose / Q000187:drug effects* / Q000378:metabolism; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D005260:Female; D006442:Glycated Hemoglobin / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D008297:Male; D024821:Metabolic Syndrome / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D008875:Middle Aged; D010919:Placebos; D019518:Postprandial Period; D055815:Young Adult
chemical_list: D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1; D001786:Blood Glucose; D006442:Glycated Hemoglobin; D010919:Placebos