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.
Aged
Anti-Obesity Agents
/ adverse effects
Body Weight
/ drug effects
Bupropion
/ adverse effects
Diabetes Mellitus, Type 2
/ complications
Female
Humans
Hypoglycemic Agents
/ therapeutic use
Incretins
/ therapeutic use
Male
Middle Aged
Naltrexone
/ adverse effects
Obesity
/ complications
Randomized Controlled Trials as Topic
Weight Loss
/ drug effects
Journal
International journal of obesity (2005)
ISSN: 1476-5497
Titre abrégé: Int J Obes (Lond)
Pays: England
ID NLM: 101256108
Informations de publication
Date de publication:
08 2021
08 2021
Historique:
received:
18
09
2020
accepted:
21
04
2021
revised:
17
03
2021
pubmed:
5
6
2021
medline:
29
1
2022
entrez:
4
6
2021
Statut:
ppublish
Résumé
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. 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). 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. 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.
Sections du résumé
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.
Identifiants
pubmed: 34083744
doi: 10.1038/s41366-021-00831-4
pii: 10.1038/s41366-021-00831-4
pmc: PMC8310797
doi:
Substances chimiques
Anti-Obesity Agents
0
Hypoglycemic Agents
0
Incretins
0
Bupropion
01ZG3TPX31
Naltrexone
5S6W795CQM
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1687-1695Informations de copyright
© 2021. The Author(s).
Références
Wing RR. Weight loss in the management of type 2 diabetes. In: Gerstein HC, Hyanes B, eds. Evidence-based diabetes care. Hamilton. B.C. Decker Inc.; 2000. p. 252–76.
Diabetes Canada Clinical Practice Guidelines Expert Committee, Wharton S, Pedersen SD, Lau DCW, Sharma AM. Weight management in diabetes. Can J Diabetes. 2018;42(Suppl 1):S124–9.
pubmed: 29650084
Greenway FL, Fujioka K, Plodkowski RA, Mudaliar S, Guttadauria M, Erickson J, et al. Effect of naltrexone plus bupropion on weight loss in overweight and obese adults (COR-I): a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial. Lancet. 2010;376:595–605.
doi: 10.1016/S0140-6736(10)60888-4
Apovian CM, Aronne L, Rubino D, Still C, Wyatt H, Burns C, et al. A randomized, phase 3 trial of naltrexone SR/bupropion SR on weight and obesity-related risk factors (COR-II). Obesity. 2013;21:935–43.
doi: 10.1002/oby.20309
Wadden TA, Foreyt JP, Foster GD, Hill JO, Klein S, O’Neil PM, et al. Weight loss with naltrexone SR/bupropion SR combination therapy as an adjunct to behavior modification: the COR-BMOD trial. Obesity. 2011;19:110–20.
doi: 10.1038/oby.2010.147
Hollander P, Gupta AK, Plodkowski R, Greenway F, Bays H, Burns C, et al. Effects of naltrexone sustained-release/bupropion sustained-release combination therapy on body weight and glycemic parameters in overweight and obese patients with type 2 diabetes. Diabetes Care. 2013;36:4022–9.
doi: 10.2337/dc13-0234
Vella A. Mechanism of action of DPP-4 inhibitors—new insights. J Clin Endocrinol Metab. 2012;97:2626–8.
doi: 10.1210/jc.2012-2396
van Bommel EJ, Muskiet MH, Tonneijck L, Kramer MH, Nieuwdorp M, van Raalte DH. SGLT2 inhibition in the diabetic kidney-from mechanisms to clinical outcome. Clin J Am Soc Nephrol. 2017;12:700–10.
doi: 10.2215/CJN.06080616
Nissen SE, Wolski KE, Prcela L, Wadden T, Buse JB, Bakris G, et al. Effect of naltrexone-bupropion on major adverse cardiovascular events in overweight and obese patients with cardiovascular risk factors: a randomized clinical trial. JAMA. 2016;315:990–1004.
doi: 10.1001/jama.2016.1558
American Diabetes Association. 9. Pharmacologic approaches to glycemic treatment: standards of medical care in diabetes-2020. Diabetes Care. 2020;43(Suppl 1):S98–S110.
doi: 10.2337/dc20-S009
Buse JB, Wexler DJ, Tsapas A, Rossing P, Mingrone G, Mathieu C, et al. 2019 update to: Management of hyperglycaemia in type 2 diabetes, 2018. A consensus report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Diabetologia. 2020;43:487–93.
Diabetes Canada Clinical Practice Guidelines Expert Committee, Lipscombe L, Butalia S, Dasgupta K, Eurich DT, MacCallum L, et al. Pharmacologic glycemic management of type 2 diabetes in adults: 2020 update. Can J Diabetes. 2020;44:575–91.
doi: 10.1016/j.jcjd.2020.08.001
Marso SP, Daniels GH, Brown-Frandsen K, Kristensen P, Mann JF, Nauck MA, et al. Liraglutide and cardiovascular outcomes in type 2 diabetes. N Engl J Med. 2016;375:311–22.
doi: 10.1056/NEJMoa1603827
Wiviott SD, Raz I, Bonaca MP, Mosenzon O, Kato ET, Cahn A, et al. Dapagliflozin and cardiovascular outcomes in type 2 diabetes. N Engl J Med. 2019;380:347–57.
doi: 10.1056/NEJMoa1812389
Hollis S, Fletcher C, Lynn F, Urban HJ, Branson J, Burger HU, et al. Best practice for analysis of shared clinical trial data. BMC Med Res Methodol. 2016;16:76.
doi: 10.1186/s12874-016-0170-y
Boehringer Ingelheim Pharmaceuticals, Inc. JARDIANCE® (empagliflozin) prescribing information (revised). 2020.