Sustained weight loss following 12-month 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 (six arms: 120, 240, and 360 microg b.i.d. and t.i.d.) or placebo in conjunction with a structured LSI program geared toward weight loss. Of the 4-month evaluable subjects (n = 270), 77% opted to continue preexisting treatment during an 8-month single-blind extension (LSI geared toward weight maintenance).

Results: At month 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 month 12, initial 4-month weight loss was regained in the placebo group but was maintained in all but the 120-microg b.i.d. group. Placebo-corrected weight loss with 120 microg t.i.d. and 360 microg b.i.d. averaged 3.2 +/- 1.2 kg (3.1 +/- 1.1% body wt) and 3.3 +/- 1.1 kg (3.1 +/- 1.0% body wt), respectively, at month 4 (both P < 0.01; 4-month evaluable n = 270) and 6.1 +/- 2.1 kg (5.6 +/- 2.1% body wt) and 7.2 +/- 2.3 kg (6.8 +/- 2.3% body wt), respectively, at month 12 (both P < 0.01; 12-month evaluable n = 146). At month 12, 40 and 43% of subjects treated with 120 microg t.i.d. and 360 microg b.i.d., respectively, achieved >or=10% weight loss (vs. 12% for placebo). Nausea, the most common adverse event with pramlintide in the 4-month 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 three-times-daily or higher-dose two-times-daily regimens, helped obese subjects achieve greater initial weight loss and enhanced long-term maintenance of weight loss.

Trial registration: ClinicalTrials.gov NCT00112021 NCT00189514.

Figures

Figure 1

Changes in body weight (kg) from baseline (month 0) for twice-daily (A) and three-times-daily (B) dosing regimens. For the double-blind study, data are presented from months 0–4 for the 4-month evaluable population (n = 270). For the single-blind extension, data are presented from months 4–12 for the 12-month evaluable population (n = 146) and at 12 months for the 12-month ITT population (LOCF) (n = 209). There are two data points for the 4-month assessment: one assessment for subjects ending the double-blind study and another for subjects entering the single-blind extension. For clarity, only month 4 and month 12 significance for double-blind study and single-blind extension, respectively, are depicted. ○ = placebo; ▴ = 120 μg pramlintide; ▵ = 240 μg pramlintide; • = 360 μg pramlintide. Data are mean ± SE. *P < 0.05 and **P < 0.01 for each pramlintide treatment group versus placebo.

Figure 2

Proportion of 12-month evaluable subjects who achieved ≥5% (A) and ≥10% (B) weight loss from baseline (month 0) to month 12. Changes in body weight from baseline (month 0) to month 12 for each 12-month evaluable individual in the placebo (C), pramlintide 120 μg t.i.d. (D), and pramlintide 360 μg b.i.d. (E) treatment arms. *P < 0.05 for each pramlintide treatment group versus placebo.