Progressive reduction in body weight after treatment with the amylin analog pramlintide in obese subjects: a phase 2, randomized, placebo-controlled, dose-escalation study.
BACKGROUND
In previous 1-yr trials, treatment with pramlintide (120 microg), an analog of the beta-cell hormone amylin, induced sustained reductions in A1C and body weight in insulin-using subjects with type 2 diabetes.


OBJECTIVE
To assess the potential of pramlintide as an antiobesity agent, we assessed the weight effect, safety, and tolerability of pramlintide in non-insulin-treated obese subjects with and without type 2 diabetes at doses greater than previously studied.


METHODS
We performed a randomized, double-blind, placebo-controlled, multicenter study.


METHODS
A total of 204 obese subjects [80/20% female/male, age 48 +/- 10 yr, and body mass index 37.8 +/- 5.6 kg/m(2) (mean +/- SD)] participated in the study.


METHODS
For 16 wk, without concomitant lifestyle intervention, subjects self-administered pramlintide (nonforced dose escalation < or = 240 microg) or placebo via sc injection three times a day before meals.


METHODS
Weight, waist circumference, tolerability, and safety were the main outcome measures.


RESULTS
Pramlintide was generally well tolerated, with 88% of subjects able to escalate to the maximum dose of 240 microg. Withdrawal rates were similar between placebo (25%) and pramlintide-treated subjects (29%). Subjects completing 16 wk of pramlintide treatment experienced placebo-corrected reductions in body weight of 3.7 +/- 0.5% (3.6 +/- 0.6 kg; P < 0.001) and waist circumference (3.6 +/- 1.1 cm; P < 0.01). Approximately 31% of pramlintide-treated subjects achieved > or =5% weight loss (vs. 2% placebo; P < 0.001). More pramlintide than placebo-treated subjects reported improvements in appetite control (72% vs. 31%), weight control (63% vs. 24%), and overall well-being (52% vs. 17%). No unexpected safety signals were observed. The most common adverse event reported was mild, transient nausea. Pramlintide-treated subjects not reporting nausea experienced weight loss similar to those who did (3.6 +/- 0.5% and 3.9 +/- 0.5%, respectively).


CONCLUSIONS
These results support continued evaluation of pramlintide as a potential treatment for obesity.
Aronne
Louis
L
Weill-Cornell Medical College, New York, NY 10021, USA.
Fujioka
Ken
K
Aroda
Vanita
V
Chen
Kim
K
Halseth
Amy
A
Kesty
Nicole C
NC
Burns
Colleen
C
Lush
Cameron W
CW
Weyer
Christian
C
D000328:Adult; D000682:Amyloid / Q000009:adverse effects / Q000627:therapeutic use*; D000886:Anthropometry; D019440:Anti-Obesity Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001835:Body Weight / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D005260:Female; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D007004:Hypoglycemic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D058228:Islet Amyloid Polypeptide; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000188:drug therapy*; D011795:Surveys and Questionnaires; D016896:Treatment Outcome
D000682:Amyloid; D019440:Anti-Obesity Agents; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D058228:Islet Amyloid Polypeptide; C105254:pramlintide