New therapies for obesity.

Obesity is a chronic disease associated with serious complications and increased mortality. Weight loss (WL) through lifestyle changes results in modest WL long-term possibly due to compensatory biological adaptations (increased appetite and reduced energy expenditure) promoting weight gain. Bariatric surgery was until recently the only intervention that consistently resulted in ≥ 15% WL and maintenance. Our better understanding of the endocrine regulation of appetite has led to the development of new medications over the last decade for the treatment of obesity with main target the reduction of appetite. The efficacy of semaglutide 2.4 mg/week-the latest glucagon-like peptide-1 (GLP-1) receptor analogue-on WL for people with obesity suggests that we are entering a new era in obesity pharmacotherapy where ≥15% WL is feasible. Moreover, the WL achieved with the dual agonist tirzepatide (GLP-1/glucose-dependent insulinotropic polypeptide) for people with type 2 diabetes and most recently also obesity, indicate that combining the GLP-1 with other gut hormones may lead to additional WL compared with GLP-1 receptor analogues alone and in the future, multi-agonist molecules may offer the potential to bridge further the efficacy gap between bariatric surgery and the currently available pharmacotherapies.

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© The Author(s) 2022. Published by Oxford University Press on behalf of the European Society of Cardiology.

Déclaration de conflit d'intérêts

Conflict of interest: D.P. has acted as speaker for Novo Nordisk and has received grants from Novo Nordisk, Novo Nordisk UK Research Foundation, Academy of Medical Sciences/Diabetes UK, and Health Education East Midlands. C.W.l.R. reports grants from the Irish Research Council, Science Foundation Ireland, Anabio, and the Health Research Board. He serves on the advisory boards of Novo Nordisk, Herbalife, GI Dynamics, Eli Lilly, Johnson & Johnson, Sanofi Aventis, AstraZeneca, Janssen, Bristol-Myers Squibb, Glia, and Boehringer Ingelheim. C.W.l.R. is a member of the Irish Society for Nutrition and Metabolism outside the area of work commented on here. He is the chief medical officer and director of the Medical Device Division of Keyron since January 2011. Both of these are unremunerated positions. C.W.l.R. was a previous investor in Keyron, which develops endoscopically implantable medical devices intended to mimic the surgical procedures of sleeve gastrectomy and gastric bypass. The product has only been tested in rodents and none of Keyron’s products are currently licensed. They do not have any contracts with other companies to put their products into clinical practice. No patients have been included in any of Keyron’s studies and they are not listed on the stock market. C.W.l.R. was gifted stock holdings in September 2021 and divested all stock holdings in Keyron in September 2021. He continues to provide scientific advice to Keyron for no remuneration. J.J.H. is a member of advisory boards for Novo Nordisk and has acted as a speaker for Novo Nordisk and Lilly. M.J.D. has acted as consultant, advisory board member and speaker for Boehringer Ingelheim, Lilly, Novo Nordisk and Sanofi, an advisory board member and speaker for AstraZeneca, an advisory board member for Janssen, Lexicon, Pfizer, and ShouTi Pharma Inc., a speaker for Napp Pharmaceuticals, Novartis, and Takeda Pharmaceuticals International Inc. and has received grants in support of investigator and investigator initiated trials from Novo Nordisk, Sanofi-Aventis, Lilly, Boehringer Ingelheim, Astrazeneca, and Janssen.