Weight loss and long-term weight loss maintenance with naltrexone ER/bupropion ER combination therapy

INTRODUCTION: For long‐term health gain, including reversal of obesity complications, 5% or more weight loss needs to be maintained. Extended‐release naltrexone (N) and bupropion (B) is approved for chronic weight management as an adjunct to lifestyle changes in adults who are overweight or have obesity. We investigated weight loss maintenance in patients treated with NB who were taking part in the NB clinical development program. METHODS: A post hoc analysis of NB trials included (1) four phase III, randomized, double‐blind, placebo‐controlled, 56‐week studies (COR‐BMOD, COR‐DM, COR I/II), (2) the cardiovascular outcomes trial (CVOT), and (3) a multicenter, randomized, controlled, open‐label trial (IGNITE). This analysis examined the percent of subjects achieving a weight loss of 5%‐10%, 10%‐15%, and ≥15% at weeks 16, 52, 104, and 208. A generalized linear mixed model assessed the likelihood of maintaining ≥5% weight loss using age, sex, baseline weight as covariates and weeks (52, 56, 104 and 208), study (COR BMOD, COR DM, COR I/COR II, NB‐404 and NB‐CVOT) and treatment (NB, placebo (PL)) as factors. RESULTS: Overall, 10,198 subjects were included in the analysis (NB = 5412; PL = 4786); 60.8% were female, 83.1% Caucasian. Average weight at baseline was 104.9 kg. 76%, 65% and 62% of subjects maintained weight loss of ≥5% at weeks 52, 104, and 208, respectively. Weight loss maintenance (≥5%) was significantly different across studies (P < 0.0001; COR‐BMOD 81%; COR I/II 74%; CORDM 69%; IGNITE 65%; CVOT 57%). A greater proportion of NB subjects maintained weight loss ≥5% over time compared to placebo, irrespective of study (75% vs 64%, P < 0.0001; Table 1). Safety and tolerability profiles were similar to those reported previously. CONCLUSION: NB treated participants who achieve ≥5% weight loss at week 16 experienced significantly greater weight loss in the short term, and weight loss maintenance over the long term, compared to placebo. Maintaining long‐term weight loss has significant implications for long‐term health.