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Clinical Trial
. 2025 May;27(5):2397-2404.
doi: 10.1111/dom.16235. Epub 2025 Feb 10.

Characterization of the effect of naltrexone/bupropion on body composition

Vanessa Tardio  1 , Peter Yin  2 , Fernando Camacho  3 , Maxime Barakat  2 , Michael A Tsoukas  1
Affiliations
Clinical Trial

Characterization of the effect of naltrexone/bupropion on body composition

Vanessa Tardio et al. Diabetes Obes Metab. 2025 May.

Abstract

Aims: Oral treatment extended-release naltrexone/bupropion (NB) leads to significant weight loss, but its effect on body composition remains unclear. We investigated changes in body composition with dual-energy x-ray absorptiometry after treatment with NB or placebo in a subgroup of participants from a randomized control phase 3 study (COR-I).

Materials and methods: Observed changes from baseline to week 52 were estimated for total, lean, and fat mass. Changes in body composition were evaluated using linear regression and adjusted for baseline covariates.

Results: The analysis included 82 participants (placebo, n = 26; NB, n = 56) with comparable baseline characteristics (age, BMI, sex). The NB group experienced a significant -7.8% change of total mass (-12.9% change in fat mass and -4.1% in lean mass), compared with a -2.8% change of total mass (-4.8% change in fat mass and -1.4% in lean mass) in the placebo group. The adjusted changes in lean-to-fat mass ratio of 0.069 in the NB group and -0.056 in the placebo group were significantly different (p < 0.05).

Conclusions: NB-induced weight loss is associated with significant reductions in total percent fat mass, increase in total percent lean mass, and change in lean-to-fat mass ratio, in comparison to placebo. Larger studies are needed to further elucidate the clinical significance of these changes and impact of a potentially healthier metabolism.

Keywords: body composition; naltrexone/bupropion; obesity; overweight; weight loss.

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Conflict of interest statement

VT has received speaker honoraria from Eli Lilly. MAT has received speaker honoraria from Bausch Health, NovoNordisk, Eli Lilly, and Boehringer‐Ingelheim. PY and MB are employees of, and shareholders in, Bausch Health Companies. FC has received consulting fees from Bausch Health, Merck Canada and Janssen Inc.

Figures

FIGURE 1
FIGURE 1
Linear regression analysis of observed change in body composition parameters. Linear regression of observed change in body composition parameters from baseline to week 52. Each dot represents an individual participant (NB, n = 56; placebo, n = 26). Values that fall above/below the dashed line (representing no change in body mass) signify a gain/loss of body mass. The dotted line represents a 25% change in lean mass and 75% change in fat mass. NB, extended‐release naltrexone/bupropion 16/360 or 32/360 mg.
FIGURE 2
FIGURE 2
Observed changes in fat and lean mass, baseline to week 52. NB, extended‐release naltrexone/bupropion 16/360 or 32/360 mg.
See this image and copyright information in PMC

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