The relationship between early weight loss and weight loss maintenance with naltrexone-bupropion therapy

Carel W le Roux; Nadège Fils-Aimé; Fernando Camacho; Errol Gould; Maxime Barakat

doi:10.1016/j.eclinm.2022.101436

The relationship between early weight loss and weight loss maintenance with naltrexone-bupropion therapy

EClinicalMedicine. 2022 May 27:49:101436. doi: 10.1016/j.eclinm.2022.101436. eCollection 2022 Jul.

Authors

Carel W le Roux¹, Nadège Fils-Aimé², Fernando Camacho³, Errol Gould⁴, Maxime Barakat²

Affiliations

¹ Diabetes Complications Research Centre, Conway Institute, University College Dublin, Ireland.
² Bausch Health, Laval, QC, Canada.
³ DAMOS Inc., Toronto, ON, Canada.
⁴ Currax Pharmaceuticals LLC, Brentwood, TN, United States of America.

Abstract

Background: Extended-release (ER) naltrexone/bupropion (NB) was associated with greater weight loss than placebo in four randomized, 56-week trials. The association of NB with longer-term maintenance of weight loss remains unknown.

Methods: We conducted a post-hoc analysis of four phase III, randomized, double-blind, placebo-controlled, 56-week studies (COR-I, COR-II, COR-BMOD, and COR-DM), the placebo-controlled cardiovascular outcomes trial LIGHT (208 weeks), and the randomized, open-label trial IGNITE (78 weeks). Included subjects were treated with NB 32 mg/360 mg or placebo, with baseline, week 16, and final time point data. The primary outcome was Kaplan-Meier-estimated weight loss maintenance in each study for up to 204 weeks.

Findings: Our analysis included data from 10,198 particpants (NB=5412; placebo=4786). Proportions of patients with ≥5% or ≥10% weight loss maintenance were numerically higher for NB vs. placebo in all studies and time points. Differences were statistically significant for ≥5% weight loss maintenance in COR-BMOD and COR-I/-II at weeks 52 and 56 and the LIGHT study at weeks 52, 104, and 208. For ≥10% weight loss maintenance, differences were statistically significant in COR-I/COR-II at weeks 52 and 56.

Interpretation: These data suggest that NB could be used as part of long-term, comprehensive weight loss and weight loss maintenance strategies.

Funding: Orexigen Therapeutics, Inc. and Bausch Health Canada.

Keywords: AHEAD, Action in Health for Diabetes; BMI, body mass index; BMOD, behavior modification therapy; CBT, cognitive behavioral therapy; CI, confidence interval; CLI, comprehensive lifestyle intervention; COR, Contrave Obesity Research; COR-BMOD; COR-DM; COR-I; COR-II; DM, diabetes mellitus; ER, extended-release; IGNITE; LIGHT; MACE, major adverse cardiovascular events; Maintenance; NAFLD, non-alcoholic fatty liver disease; NB, naltrexone/bupropion; NWCR, National Weight Control Registry; Naltrexone/bupropion; SAEs, serious adverse events; SD, standard deviation; SMD, standardized mean difference; Weight loss.