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Stimulation of Cholecystokinin‐A Receptors With GI181771X does not Cause Weight Loss in Overweight or Obese Patients
Author(s) -
Jordan J,
Greenway FL,
Leiter LA,
Li Z,
Jacobson P,
Murphy K,
Hill J,
Kler L,
Aftring RP
Publication year - 2008
Publication title -
clinical pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.941
H-Index - 188
eISSN - 1532-6535
pISSN - 0009-9236
DOI - 10.1038/sj.clpt.6100272
Subject(s) - cholecystokinin , overweight , weight loss , stimulation , receptor , medicine , endocrinology , obesity , cholecystokinin receptor
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 ≥30 or ≥27 kg/m 2 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. Clinical Pharmacology & Therapeutics (2008) doi: 10.1038/sj.clpt.6100272