Context: In previous 1-yr trials, treatment with pramlintide (120 g), an analog of the ␤-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

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... randomized, double-blind, placebocontrolled, multicenter study. Patients: A total of 204 obese subjects [80/20% female/male, age 48 Ϯ 10 yr, and body mass index 37.8 Ϯ 5.6 kg/m 2 (mean Ϯ SD)] participated in the study. Intervention: For 16 wk, without concomitant lifestyle intervention, subjects self-administered pramlintide (nonforced dose escalation Յ 240 g) 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 g. 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 Ϯ 0.5% (3.6 Ϯ 0.6 kg; P Ͻ 0.001) and waist circumference (3.6 Ϯ 1.1 cm; P Ͻ 0.01). Approximately 31% of pramlintide-treated subjects achieved Ն5% weight loss (vs. 2% placebo; P Ͻ 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 Ϯ 0.5% and 3.9 Ϯ 0.5%, respectively). Conclusion: These results support continued evaluation of pramlintide as a potential treatment for obesity.