Stimulation of cholecystokinin-A receptors with GI181771X does not cause weight loss in overweight or obese patients

Clin Pharmacol Ther. 2008 Feb;83(2):281-7. doi: 10.1038/sj.clpt.6100272. Epub 2007 Jun 27.

Abstract

Cholecystokinin (CCK) decreases meal size through activation of CCK-A receptors on vagal afferents. We tested the hypothesis that the selective CCK-A agonist GI181771X induces weight loss in obese patients. Patients with body mass index > or = 30 or > or = 27 kg/m2 with concomitant risk factors were randomized to 24-week, double-blind treatment with different GI181771X doses or matching placebo together with a hypocaloric diet. The primary efficacy end point was the absolute change in body weight. To monitor pancreatic and gallbladder effects, patients underwent abdominal ultrasound and magnetic resonance imaging before and after treatment. We randomized 701 patients to double-blind treatment. GI181771X did not reduce body weight and had no effect on waist circumference or other cardiometabolic risk markers. Gastrointestinal side effects were more common with GI181771X than with placebo treatment, whereas hepatobiliary or pancreatic abnormalities did not occur. CCK-A by itself does not have a central role in long-term energy balance.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Anti-Obesity Agents / adverse effects
  • Anti-Obesity Agents / therapeutic use*
  • Benzodiazepines / adverse effects
  • Benzodiazepines / therapeutic use*
  • Caloric Restriction*
  • Combined Modality Therapy
  • Double-Blind Method
  • Female
  • Gallbladder / drug effects
  • Humans
  • Liver / drug effects
  • Magnetic Resonance Imaging
  • Male
  • Middle Aged
  • Obesity / diet therapy
  • Obesity / drug therapy*
  • Obesity / metabolism
  • Obesity / pathology
  • Pancreas / drug effects
  • Receptor, Cholecystokinin A / agonists*
  • Receptor, Cholecystokinin A / metabolism
  • Time Factors
  • Treatment Outcome
  • Ultrasonography
  • Weight Loss / drug effects*

Substances

  • Anti-Obesity Agents
  • GI 181771X
  • Receptor, Cholecystokinin A
  • Benzodiazepines