1. ¹Franz-Volhard Clinical Research Center, Helios Klinikum and Medical Faculty of the Charité, Berlin, Germany
2. ²Pennington Biomedical Research Center, Louisiana State University System, Baton Rouge, Louisiana, USA
3. ³St Michael's Hospital, University of Toronto, Toronto, Ontario, Canada
4. ⁴University of California, Los Angeles, California, USA
5. ⁵Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska University Hospital, Göteborg, Sweden
6. ⁶GlaxoSmithKline Inc., King of Prussia, Pennsylvania, USA

Correspondence: J Jordan, jens.jordan@charite.de

Received 28 February 2007; Accepted 24 May 2007; Published online 27 June 2007.

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 30 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.