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 mu g), 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 <= 240 mu 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 mu 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 +/- 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.