Effect of NPY5R antagonist MK-0557 on weight regain after very-low-calorie diet-induced weight loss.

Abstract

OBJECTIVE:

To evaluate whether MK-0557, a highly selective, orally administered neuropeptide Y Y5 receptor antagonist, could limit weight regain after very-low-calorie diet (VLCD)-induced weight loss.

RESEARCH METHODS AND PROCEDURES:

We enrolled 502 patients 18 to 65 years of age with a BMI of 30 to 43 kg/m2. Patients were placed on a VLCD (800 kcal/d liquid diet) for 6 weeks. Patients who lost>or=6% of initial body weight (n=359) were randomized to 52 weeks of 1 mg/d MK-0557 or placebo and maintained on a hypocaloric diet (300 kcal below weight maintenance requirements).

RESULTS:

In randomized patients, the VLCD was associated with an average weight loss of 9.1 kg. After 12 weeks of double-blind treatment, weight began to gradually increase for both placebo- and MK-0557-treated patients. The mean weight change (95% confidence interval) from baseline at the end of the VLCD to Week 52 was +3.1 (2.1, 4.0) and +1.5 (0.5, 2.4) kg for patients treated with placebo and MK-0557, respectively. The difference of 1.6 kg between the two groups was significant (p=0.014). Secondary endpoints, such as blood pressure, lipid profile, insulin, and leptin, as well as waist circumference and quality-of-life measurements, did not show significant differences between MK-0557 and placebo treatments.

DISCUSSION:

Although the difference in weight regain between placebo- and MK-0557-treated patients was statistically significant, the magnitude of the effect was small and not clinically meaningful. Antagonism of the neuropeptide Y Y5 receptor is not an efficacious treatment strategy for reducing weight regain after VLCD.

• Authors: Ngozi Erondu, Thomas Wadden, Ira Gantz, Bret Musser, Allison Martin Nguyen, Harold Bays, George Bray, Patrick M O'Neil, Arnaud Basdevant, Keith D Kaufman, Steven B Heymsfield, John M Amatruda
• Journal: Obesity (Silver Spring, Md.) (Obesity (Silver Spring)) Vol. 15 Issue 4 Pg. 895-905 (Apr 2007) ISSN: 1930-7381 [Print] United States
• PMID: 17426325 (Publication Type: Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Cyclohexanes
• Neurotransmitter Agents
• Placebos
• Pyrazoles
• Receptors, Neuropeptide Y
• Spiro Compounds
• neuropeptide Y5 receptor
• spiro(cyclohexane-1,3'(1'H)-furo(3,4-C)pyridine)-4-carboxamide, N-(1-(2-fluorophenyl)-1h-pyrazol-3-yl)-1'-oxo-, trans-

Topics

• Adolescent
• Adult
• Aged
• Body Mass Index
• Caloric Restriction
• Cyclohexanes (therapeutic use)
• Double-Blind Method
• Female
• Humans
• Male
• Middle Aged
• Neurotransmitter Agents (metabolism)
• Obesity (drug therapy)
• Placebos
• Pyrazoles (therapeutic use)
• Receptors, Neuropeptide Y (antagonists & inhibitors)
• Spiro Compounds (therapeutic use)
• Weight Loss