Glucagon and GLP-1 receptor dual agonist survodutide for obesity: a randomised, double-blind, placebo-controlled, dose-finding phase 2 trial.
Journal
The lancet. Diabetes & endocrinology
ISSN: 2213-8595
Titre abrégé: Lancet Diabetes Endocrinol
Pays: England
ID NLM: 101618821
Informations de publication
Date de publication:
05 Feb 2024
05 Feb 2024
Historique:
received:
31
08
2023
revised:
16
10
2023
accepted:
16
11
2023
medline:
9
2
2024
pubmed:
9
2
2024
entrez:
8
2
2024
Statut:
aheadofprint
Résumé
Obesity is a widespread and chronic condition that requires long-term management; research into additional targets to improve treatment outcomes remains a priority. This study aimed to investigate the safety, tolerability, and efficacy of glucagon receptor-GLP-1 receptor dual agonist survodutide (BI 456906) in obesity management. In this randomised, double-blind, placebo-controlled, dose-finding phase 2 trial conducted in 43 centres in 12 countries, we enrolled participants (aged 18-75 years, BMI ≥27 kg/m Between March 30, 2021, and Nov 11, 2021, we enrolled 387 participants; 386 (100%) participants were treated (0·6 mg, n=77; 2·4 mg, n=78; 3·6 mg, n=77; 4·8 mg, n=77; placebo n=77) and 233 (60·4%) of 386 completed the 46-week treatment period (187 [61%] of 309 receiving survodutide; 46 [60%] of 77 receiving placebo). When analysed according to planned treatment, mean (95% CI) changes in bodyweight from baseline to week 46 were -6·2% (-8·3 to -4·1; 0·6 mg); -12·5% (-14·5 to -10·5; 2·4 mg); -13·2% (-15·3 to -11·2; 3·6 mg); -14·9% (-16·9 to -13·0; 4·8 mg); -2·8% (-4·9 to -0·7; placebo). Adverse events occurred in 281 (91%) of 309 survodutide recipients and 58 (75%) of 77 placebo recipients; these were primarily gastrointestinal in 232 (75%) of 309 survodutide recipients and 32 (42%) of 77 placebo recipients. All tested survodutide doses were tolerated, and dose-dependently reduced bodyweight. Boehringer Ingelheim.
Sections du résumé
BACKGROUND
BACKGROUND
Obesity is a widespread and chronic condition that requires long-term management; research into additional targets to improve treatment outcomes remains a priority. This study aimed to investigate the safety, tolerability, and efficacy of glucagon receptor-GLP-1 receptor dual agonist survodutide (BI 456906) in obesity management.
METHODS
METHODS
In this randomised, double-blind, placebo-controlled, dose-finding phase 2 trial conducted in 43 centres in 12 countries, we enrolled participants (aged 18-75 years, BMI ≥27 kg/m
FINDINGS
RESULTS
Between March 30, 2021, and Nov 11, 2021, we enrolled 387 participants; 386 (100%) participants were treated (0·6 mg, n=77; 2·4 mg, n=78; 3·6 mg, n=77; 4·8 mg, n=77; placebo n=77) and 233 (60·4%) of 386 completed the 46-week treatment period (187 [61%] of 309 receiving survodutide; 46 [60%] of 77 receiving placebo). When analysed according to planned treatment, mean (95% CI) changes in bodyweight from baseline to week 46 were -6·2% (-8·3 to -4·1; 0·6 mg); -12·5% (-14·5 to -10·5; 2·4 mg); -13·2% (-15·3 to -11·2; 3·6 mg); -14·9% (-16·9 to -13·0; 4·8 mg); -2·8% (-4·9 to -0·7; placebo). Adverse events occurred in 281 (91%) of 309 survodutide recipients and 58 (75%) of 77 placebo recipients; these were primarily gastrointestinal in 232 (75%) of 309 survodutide recipients and 32 (42%) of 77 placebo recipients.
INTERPRETATION
CONCLUSIONS
All tested survodutide doses were tolerated, and dose-dependently reduced bodyweight.
FUNDING
BACKGROUND
Boehringer Ingelheim.
Identifiants
pubmed: 38330987
pii: S2213-8587(23)00356-X
doi: 10.1016/S2213-8587(23)00356-X
pii:
doi:
Banques de données
ClinicalTrials.gov
['NCT04667377']
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Informations de copyright
Copyright © 2024 Elsevier Ltd. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of interests The authors meet criteria for authorship as recommended by the International Committee of Medical Journal Editors (ICMJE) and did not receive payment related to the development of this manuscript. ClR has received personal fees from Boehringer Ingelheim, Eli Lilly, GI Dynamics, Gila Pharmaceuticals, Herbalife, Johnson & Johnson, Keyron, Novo Nordisk, and Zealand Pharma outside the submitted work. OS has received research support from Alnylam, Anji, AstraZeneca, Boehringer Ingelheim, CRISPR Therapeutics, Eli Lilly, Gilead, Janssen, Kowa, Medicago, Moderna, Novartis, Novo Nordisk, Pfizer, Sanofi, ViaCyte, and Zucara Therapeutics; speaker bureau fees from Amgen, AstraZeneca, Bausch Health, HLS Therapeutics, Janssen, LMC, Novo Nordisk, and Sanofi; and consultancy fees from Amgen, Bayer, Eli Lilly, Novo Nordisk, and Sanofi. ES, AMH, and AU are employees of Boehringer Ingelheim. KJL declares no competing interests.