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


METHODS
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.


CONCLUSIONS
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.
Erondu
Ngozi
N
Department of Clinical Research, Metabolism, Merck Research Laboratories, 126 E. Lincoln Avenue, PO Box 2000, RY34A-A238, Rahway, NJ 07065-0900, USA. Ngozi_Erondu@Merck.com
Wadden
Thomas
T
Gantz
Ira
I
Musser
Bret
B
Nguyen
Allison Martin
AM
Bays
Harold
H
Bray
George
G
O'Neil
Patrick M
PM
Basdevant
Arnaud
A
Kaufman
Keith D
KD
Heymsfield
Steven B
SB
Amatruda
John M
JM
D000293:Adolescent; D000328:Adult; D000368:Aged; D015992:Body Mass Index; D031204:Caloric Restriction; D003510:Cyclohexanes / Q000627:therapeutic use*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D018377:Neurotransmitter Agents / Q000378:metabolism; D009765:Obesity / Q000188:drug therapy*; D010919:Placebos; D011720:Pyrazoles / Q000627:therapeutic use*; D017476:Receptors, Neuropeptide Y / Q000037:antagonists & inhibitors*; D013141:Spiro Compounds / Q000627:therapeutic use*; D015431:Weight Loss
D003510:Cyclohexanes; D018377:Neurotransmitter Agents; D010919:Placebos; D011720:Pyrazoles; D017476:Receptors, Neuropeptide Y; D013141:Spiro Compounds; C100568:neuropeptide Y5 receptor; C515547:spiro(cyclohexane-1,3'(1'H)-furo(3,4-C)pyridine)-4-carboxamide, N-(1-(2-fluorophenyl)-1h-pyrazol-3-yl)-1'-oxo-, trans-