title: Effects of MK-0941, a novel glucokinase activator, on glycemic control in insulin-treated patients with type 2 diabetes.
abstract: OBJECTIVE
  To assess the efficacy and safety of MK-0941, a glucokinase activator (GKA), when added to stable-dose insulin glargine in patients with type 2 diabetes.
  
  
  METHODS
  In this double-blind study, 587 patients taking stable-dose insulin glargine (±metformin ≥1,500 mg/day) were randomized (1:1:1:1:1) to MK-0941 10, 20, 30, or 40 mg or matching placebo t.i.d. before meals (a.c.). This study included an initial 14-week, dose-ranging phase followed by a 40-week treatment phase during which patients were to be uptitrated as tolerated to 40 mg (or placebo) t.i.d. a.c. The primary efficacy end point was change from baseline in A1C at Week 14.
  
  
  RESULTS
  At Week 14, A1C and 2-h postmeal glucose (PMG) improved significantly versus placebo with all MK-0941 doses. Maximal placebo-adjusted least squares mean changes from baseline in A1C (baseline A1C 9.0%) and 2-h PMG were -0.8% and -37 mg/dL (-2 mmol/L), respectively. No significant effects on fasting plasma glucose were observed at any dose versus placebo. By 30 weeks, the initial glycemic responses noted at 14 weeks were not sustained. MK-0941 at one or more doses was associated with significant increases in the incidence of hypoglycemia, triglycerides, systolic blood pressure, and proportion of patients meeting criteria for predefined limits of change for increased diastolic blood pressure.
  
  
  CONCLUSIONS
  In patients receiving stable-dose insulin glargine, the GKA MK-0941 led to improvements in glycemic control that were not sustained. MK-0941 was associated with an increased incidence of hypoglycemia and elevations in triglycerides and blood pressure.
authors: Merck Sharp & Dohme Corp., Rahway, New Jersey, USA.
authors: Gary E
authors: GE
authors: Meininger
authors: Russell
authors: R
authors: Scott
authors: Maria
authors: M
authors: Alba
authors: Yue
authors: Y
authors: Shentu
authors: Edmund
authors: E
authors: Luo
authors: Himal
authors: H
authors: Amin
authors: Michael J
authors: MJ
authors: Davies
authors: Keith D
authors: KD
authors: Kaufman
authors: Barry J
authors: BJ
authors: Goldstein
mesh_terms: D000328:Adult; D000368:Aged; D001549:Benzamides / Q000009:adverse effects / Q000627:therapeutic use*; D001786:Blood Glucose / Q000187:drug effects*; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D004311:Double-Blind Method; D020536:Enzyme Activators / Q000627:therapeutic use*; D005941:Glucokinase / Q000378:metabolism*; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D007003:Hypoglycemia / Q000139:chemically induced; D000069036:Insulin Glargine; D049528:Insulin, Long-Acting / Q000627:therapeutic use*; D008875:Middle Aged; D013450:Sulfones / Q000009:adverse effects / Q000627:therapeutic use*
chemical_list: D001549:Benzamides; D001786:Blood Glucose; D020536:Enzyme Activators; D005941:Glucokinase; D006442:Glycated Hemoglobin; D000069036:Insulin Glargine; D049528:Insulin, Long-Acting; D013450:Sulfones; C569222:3-((6-(ethylsulfonyl)-3-pyridinyl)oxy)-5-(2-hydroxy-1-methylethoxy)-N-(1-methyl-1H-pyrazol-3-yl)benzamide