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Review
. 2023 Jul;23(4):337-346.
doi: 10.7861/clinmed.2023-0144.

Future therapies for obesity

Eka Melson  1 , Alexander Dimitri Miras  2 , Dimitris Papamargaritis  3
Affiliations
Review

Future therapies for obesity

Eka Melson et al. Clin Med (Lond). 2023 Jul.

Abstract

Obesity is a chronic disease associated with increased morbidity and mortality. Bariatric surgery can lead to sustained long-term weight loss (WL) and improvement in multiple obesity-related complications, but it is not scalable at the population level. Over the past few years, gut hormone-based pharmacotherapies for obesity and type 2 diabetes mellitus (T2DM) have rapidly evolved, and combinations of glucagon-like peptide 1 (GLP1) with other gut hormones (glucose-dependent insulinotropic polypeptide (GIP), glucagon, and amylin) as dual or triple agonists are under investigation to enhance and complement the effects of GLP1 on WL and obesity-related complications. Tirzepatide, a dual agonist of GLP1 and GIP receptors, marks a new era in obesity pharmacotherapy in which a combination of gut hormones could approach the WL achieved with bariatric surgery. In this review, we discuss emerging obesity treatments with a focus on gut hormone combinations and the concept of a multimodal approach for obesity management.

Keywords: gut hormones; obesity; pharmacotherapy; tirzepatide.

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Conflict of interest statement

EM declares no conflict of interest. ADM has received grants or contracts from Fractyl, Novo Nordisk and Randox, and payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing or educational events from Novo Nordisk, AstraZeneca, Currax and Boehringer Ingelheim. DP has acted as a 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.

Figures

Fig 1.
Fig 1.
The mean weight loss achieved at approximately 1 year follow-up with moderate-intensity lifestyle interventions (500 kcal/day deficit diet and advice to exercise for 150 min/week), currently available pharmacotherapies (and tirzepatide) and bariatric surgery in people without diabetes. *Not approved yet for obesity management; **approved in the USA, but not in Europe.
Fig 2.
Fig 2.
Pharmacotherapies under investigation based on a combination of glucagon-like peptide 1 (GLP1) with other gut hormones and the actions related to agonism of each gut hormone and antagonism of glucose-dependent insulinotropic polypeptide (GIP). PYY = Peptide YY; *action in preclinical models; **clinical data not available yet.
See this image and copyright information in PMC

References

    1. Bray GA, Kim KK, Wilding JPH. Obesity: a chronic relapsing progressive disease process. A position statement of the World Obesity Federation. Obes Rev 2017;18:715–23. - PubMed
    1. Baker C. Obesity statistics. London: House of Commons Library, 2023.
    1. Perdomo CM, Cohen RV, Sumithran P, et al. . Contemporary medical, device, and surgical therapies for obesity in adults. Lancet 2023;401:1116–30. - PubMed
    1. Busetto L, Bettini S, Makaronidis J, et al. . Mechanisms of weight regain. Eur J Intern Med 2021;93:3–7. - PubMed
    1. Tahrani AA, Morton J. Benefits of weight loss of 10% or more in patients with overweight or obesity: a review. Obesity 2022;30:802–40. - PubMed

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