Sustained Weight Loss Following 12 Months Pramlintide Treatment as an Adjunct to Lifestyle Intervention in Obesity

Abstract

Objective- To assess long-term weight-loss efficacy and safety of pramlintide used at different dosing regimens and in conjunction with lifestyle intervention (LSI).

Research design and methods In a 4-month, double-blind, placebo-controlled, dose-ranging study, 411 obese subjects were randomized to receive pramlintide (6 arms: 120, 240, 360 mg, BID/TID) or placebo in conjunction with a structured LSI program geared toward weight-loss. Of the 4-Mo evaluable subjects (N=270), 77% opted to continue pre-existing treatment during an 8-Mo single-blind extension (LSI geared toward weight maintenance).

Results At Mo-4, mean weight-loss from baseline in the pramlintide arms ranged from 3.8±0.7 to 6.1±0.8 kg (2.8±0.8 kg with placebo). By Mo-12, initial 4-mo weight-loss was regained in the placebo group, but was maintained in all but the 120 BID group. Placebo-corrected weight-loss with 120 TID and 360 BID averaged 3.2±1.2 kg (3.1±1.1%) and 3.3±1.1 kg (3.1±1.0%), respectively, at Mo-4 (both P<0.01; 4-Mo Evaluable N=270) and 6.1±2.1 kg (5.6±2.1 %) and 7.2±2.3 kg (6.8±2.3%), respectively, at Mo-12 (both P<0.01; 12-Mo Evaluable N=146). At Mo-12, 40 and 43% of subjects treated with 120 TID and 360 BID, respectively, achieved ≥10% weight-loss (versus 12% for placebo). Nausea, the most common adverse event with pramlintide in the 4-mo study (9-29% pramlintide vs 2% placebo), was generally mild-to-moderate and occurred in <10% of subjects during the extension.

Conclusions- When used over 12-months as an adjunct to LSI, pramlintide treatment, with low dose TID or higher dose BID regimens, helped obese subjects achieve greater initial weight-loss and enhanced long-term maintenance of weight-loss.