Progressive reduction in body weight after treatment with the amylin analog pramlintide in obese subjects: a phase 2, randomized, placebo-controlled, dose-escalation study

J Clin Endocrinol Metab. 2007 Aug;92(8):2977-83. doi: 10.1210/jc.2006-2003. Epub 2007 May 15.

Abstract

Context: 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.

Design/setting: We performed a randomized, double-blind, placebo-controlled, multicenter study.

Patients: 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.

Intervention: 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.

Main outcome measures: 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).

Conclusion: These results support continued evaluation of pramlintide as a potential treatment for obesity.

Publication types

  • Clinical Trial, Phase II
  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Amyloid / adverse effects
  • Amyloid / therapeutic use*
  • Anthropometry
  • Anti-Obesity Agents / adverse effects
  • Anti-Obesity Agents / therapeutic use*
  • Body Weight / drug effects*
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Female
  • Glycated Hemoglobin A / metabolism
  • Humans
  • Hypoglycemic Agents / adverse effects
  • Hypoglycemic Agents / therapeutic use*
  • Islet Amyloid Polypeptide
  • Male
  • Middle Aged
  • Obesity / drug therapy*
  • Surveys and Questionnaires
  • Treatment Outcome

Substances

  • Amyloid
  • Anti-Obesity Agents
  • Glycated Hemoglobin A
  • Hypoglycemic Agents
  • Islet Amyloid Polypeptide
  • pramlintide