Efficacy and safety of intranasal peptide YY3-36 for weight reduction in obese adults.
BACKGROUND
The gastrointestinal peptide hormone, peptide YY(3-36) (PYY(3-36)), is implicated to be a postprandial satiety factor.


OBJECTIVE
The aim of this study is to assess the safety, tolerability, and efficacy of intranasal PYY(3-36) to induce weight loss in obese patients.


METHODS
The study was designed as a randomized, 2-wk, single-blind placebo run-in followed by a 12-wk double-blind, placebo-controlled treatment period.


METHODS
The study was set within a private and institutional practice.


METHODS
A total of 133 obese patients (body mass index, 30-43 kg/m(2); age, 18-65 yr) participated in the study.


METHODS
Placebo or 200- or 600-microg PYY(3-36) was administered as an intranasal spray 20 min before breakfast, lunch, and dinner in conjunction with a hypocaloric diet and exercise.


METHODS
Body weight was the main outcome measure.


RESULTS
The number of patients completing 12 wk on the drug was 38 of 43 (88%), 31 of 44 (70%), and 12 of 46 (26%) for placebo, 200 microg three times a day (t.i.d.) and 600 microg t.i.d., respectively. In the 600 microg t.i.d. group, 27 of 46 (59%) patients discontinued due to nausea and vomiting. Among all randomized patients who took at least one drug dose and had a postbaseline measurement, the mean body weight change from baseline was -2.8, -3.7, and -1.4 kg for placebo, 200 and 600 microg, respectively. The least squares mean difference (95% confidence interval) between placebo and 200 microg was -0.9 (-2.6, 0.7) kg (P = 0.251). A difference of 2.11 kg was sought. No meaningful inference can be drawn from the few patients who completed the study on 600 microg.


CONCLUSIONS
Intranasal PYY(3-36) as administered at these intervention doses and preprandial timing is not efficacious in inducing weight loss in obese patients after 12 wk of treatment.
Gantz
Ira
I
Clinical Research, Metabolism, Merck Research Laboratories, 126 East Lincoln Avenue, P.O. Box 2000, RY34A-A202, Rahway, NJ 07065-0900, USA. Ira_Gantz@Merck.com
Erondu
Ngozi
N
Mallick
Madhuja
M
Musser
Bret
B
Krishna
Rajesh
R
Tanaka
Wesley K
WK
Snyder
Karen
K
Stevens
Cathy
C
Stroh
Mark A
MA
Zhu
Haiyuan
H
Wagner
John A
JA
Macneil
Douglas J
DJ
Heymsfield
Steven B
SB
Amatruda
John M
JM
D000281:Administration, Intranasal; D000293:Adolescent; D000328:Adult; D000368:Aged; D015992:Body Mass Index; D001835:Body Weight / Q000187:drug effects; D004038:Diet, Reducing; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005081:Exercise Therapy; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000188:drug therapy*; D010446:Peptide Fragments; D019894:Peptide YY / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D016896:Treatment Outcome; D015431:Weight Loss / Q000187:drug effects
D010446:Peptide Fragments; D019894:Peptide YY; C061785:peptide YY (3-36)