Weight loss, HbA1c reduction, and tolerability of cetilistat in a randomized, placebo-controlled phase 2 trial in obese diabetics: comparison with orlistat (Xenical)

Obesity (Silver Spring). 2010 Jan;18(1):108-15. doi: 10.1038/oby.2009.155. Epub 2009 May 21.

Abstract

The objective of this multicenter, randomized, double-blind study was to determine the efficacy and safety of cetilistat and orlistat relative to placebo in obese patients with type 2 diabetes, on metformin. Following a 2-week run-in, patients were randomized to placebo, cetilistat (40, 80, or 120 mg three times daily), or orlistat 120 mg t.i.d., for 12 weeks. The primary endpoint was absolute change in body weight from baseline. Secondary endpoints included other measures of obesity and glycemic control. Similar reductions in body weight were observed in patients receiving cetilistat 80 or 120 mg t.i.d. or 120 mg t.i.d. orlistat; these reductions were significant vs. placebo (3.85 kg, P = 0.01; 4.32 kg, P = 0.0002; 3.78 kg, P = 0.008). In the 40 mg t.i.d. and placebo groups, reductions were 2.94 kg, P = 0.958 and 2.86 kg, respectively. Statistically significant reductions in glycosylated hemoglobin (HbA(1c)) were noted. Cetilistat was well tolerated, and showed fewer discontinuations due to adverse events (AEs) than in the placebo and orlistat groups. Discontinuation in the orlistat group was significantly worse than in the 120 mg cetilistat and placebo groups and was entirely due to gastrointestinal (GI) AEs. Treatment with cetilistat 80 or 120 mg t.i.d., or with orlistat 120 mg t.i.d., significantly reduced body weight and improved glycemic control relative to placebo in obese diabetic patients. Cetilistat was well tolerated with the number of discontinuations due to AEs being similar to placebo.

Trial registration: ClinicalTrials.gov NCT00156897.

Publication types

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

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Benzoxazines / therapeutic use*
  • Diabetes Mellitus, Type 2 / complications*
  • Diabetes Mellitus, Type 2 / drug therapy
  • Diabetes Mellitus, Type 2 / metabolism
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Female
  • Glycated Hemoglobin A / metabolism*
  • Humans
  • Hypoglycemic Agents / therapeutic use
  • Intention to Treat Analysis
  • Lactones / therapeutic use*
  • Lipase / antagonists & inhibitors
  • Male
  • Metformin / therapeutic use
  • Middle Aged
  • Obesity / complications
  • Obesity / drug therapy*
  • Obesity / metabolism
  • Orlistat
  • Patient Selection
  • Treatment Outcome
  • Weight Loss / drug effects*

Substances

  • Benzoxazines
  • Glycated Hemoglobin A
  • Hypoglycemic Agents
  • Lactones
  • hemoglobin A1c protein, human
  • Metformin
  • Orlistat
  • Lipase
  • cetilistat

Associated data

  • ClinicalTrials.gov/NCT00156897
  • ISRCTN/ISRCTN62647464