Progressive Reduction in Body Weight after Treatment with the Amylin Analog Pramlintide in Obese Subjects: A Phase 2, Randomized, Placebo-Controlled, Dose-Escalation Study

Context: In previous 1-yr trials, treatment with pramlintide (120 μg), an analog of the β-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/m2 (mean ± sd)] participated in the study. Intervention: For 16 wk, without concomitant lifestyle intervention, subjects self-administered pramlintide (nonforced dose escalation ≤ 240 μg) 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 μg. 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 ≥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.