title: Progressive reduction in body weight after treatment with the amylin analog pramlintide in obese subjects: a phase 2, randomized, placebo-controlled, dose-escalation study.
abstract: 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.
authors.affiliation: Weill-Cornell Medical College, New York, NY 10021, USA.
authors.forename: Louis
authors.initials: L
authors.lastname: Aronne
authors.forename: Ken
authors.initials: K
authors.lastname: Fujioka
authors.forename: Vanita
authors.initials: V
authors.lastname: Aroda
authors.forename: Kim
authors.initials: K
authors.lastname: Chen
authors.forename: Amy
authors.initials: A
authors.lastname: Halseth
authors.forename: Nicole C
authors.initials: NC
authors.lastname: Kesty
authors.forename: Colleen
authors.initials: C
authors.lastname: Burns
authors.forename: Cameron W
authors.initials: CW
authors.lastname: Lush
authors.forename: Christian
authors.initials: C
authors.lastname: Weyer
mesh_terms: 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
chemical_list: D000682:Amyloid; D019440:Anti-Obesity Agents; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D058228:Islet Amyloid Polypeptide; C105254:pramlintide