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. 2021 Aug;45(8):1687-1695.
doi: 10.1038/s41366-021-00831-4. Epub 2021 Jun 3.

Extended-release naltrexone/bupropion is safe and effective among subjects with type 2 diabetes already taking incretin agents: a post-hoc analysis of the LIGHT trial

Sean Wharton  1 , Peter Yin  2 , Melonie Burrows  2 , Errol Gould  3 , Jessica Blavignac  2 , Rebecca A G Christensen  4 , Elham Kamran  4 , Fernando Camacho  5 , Maxime Barakat  2
Affiliations

Extended-release naltrexone/bupropion is safe and effective among subjects with type 2 diabetes already taking incretin agents: a post-hoc analysis of the LIGHT trial

Sean Wharton et al. Int J Obes (Lond). 2021 Aug.

Abstract

Background: Extended-release naltrexone/bupropion (NB) is indicated for chronic weight management. Incretin agents are recommended for patients with type 2 diabetes. This analysis looked at the add-on of NB to incretins to see if weight loss could occur in patients already stabilized on incretin agents.

Methods: This was a post-hoc analysis of NB vs. placebo (PL) among subjects with type 2 diabetes stable on an incretin agent prior to randomization in a double-blind, PL-controlled cardiovascular outcome trial (N = 1317).

Results: Over 1 year, mean weight loss was significantly greater among NB patients vs. PL among those taking DPP-4i (mean absolute difference 4.6% [p < 0.0001]) and those taking GLP-1RAs (mean absolute difference 5.2%, p < 0.0001). Proportions of subjects achieving 5% weight loss were significantly greater for NB vs. PL at weeks 26 and 52 among those taking DPP-4is or GLP-1RAs. There were no significant differences in effectiveness observed between NB + DPP-4i and NB + GLP-1RA or between PL + DPP-4i and PL + GLP-1RA in any of the analyses. Serious adverse events were reported by 9.1% and 11.1% for PL + DPP-4i and PL + GLP-1RA, respectively, and 13.3% and 12.4% of NB + DPP-4i and NB + GLP-1RA, respectively.

Conclusion: NB appears to be effective in reducing weight in patients with T2DM and obesity/overweight who are taking DPP-4ihibitors or GLP-1RA. The SAE rates in all arms of this analysis were lower than have been reported in other cardiovascular outcome trials in type 2 diabetes.

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Conflict of interest statement

SW is the owner and director of Wharton Medical Clinic (WMC). He has previously received funding in the form of grants for research from the Canadian Institutes of Health Research and Mitacs. He has also received funding from Novo Nordisk, Bausch Health Canada Inc., Eli Lilly and Company, Janssen Pharmaceuticals, and AstraZeneca for advisory work. EK and RAGC are currently employed by the Wharton Medical Clinic. PY is an employee of Bausch Health Companies. MB (Melonie Burrows) is a former employee of Bausch Health Companies. JB and MB (Maxime Barakat) are employees of, and shareholders in, Bausch Health Companies. FC received consulting fees from Bausch Health, Abbvie Corporation, and Janssen Inc. EG is an employee of Currax Pharmaceuticals LLC.

Figures

Fig. 1
Fig. 1. Patient disposition of populations of interest.
Total population includes all patients from LIGHT who were on a DPP-4i or GLP-1RA at baseline and received study treatment. Week 52 completers are those in the total population who remained on study therapy at week 52. Week 16 responders are those in the total population who experienced a weight loss of at least 5% at week 16.
Fig. 2
Fig. 2. Percent weight changes.
A Total population*, B week 52 completers†; C week 16 responders‡. §Statistically significant difference, NB vs. PL at week 52. *All subjects taking a DPP-4i or GLP-1RA at baseline. †Subjects from the total population who remained on study treatment through to week 52. ‡Subjects from the total population who had a weight loss of ≥5% from baseline at week 16. The number of subjects in the model is lower than at baseline since not all subjects have post-baseline data. Note that the attrition from week 16 to week 26 in the total population includes those patients who did not achieve 2% weight loss at week 16 (discontinued from study medication as per LIGHT study protocol and not included in this analysis). Numbers discontinuing at week 16 in the total population (A): NB + DPP-4i, n = 66; NB + GLP-1RA, n = 53; PL + DPP-4i, n = 155; PL + GLP-1RA, n = 173.
Fig. 3
Fig. 3. Categorical weight loss, total population at weeks 26 and 52.
A ≥5% Weight loss from baseline; B ≥10% weight loss from baseline.
See this image and copyright information in PMC

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