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Review
. 2024 Aug 30:75:102782.
doi: 10.1016/j.eclinm.2024.102782. eCollection 2024 Sep.

GLP-1 single, dual, and triple receptor agonists for treating type 2 diabetes and obesity: a narrative review

Nasreen Alfaris  1 , Stephanie Waldrop  2 , Veronica Johnson  3 , Brunna Boaventura  4 , Karla Kendrick  5 , Fatima Cody Stanford  6
Affiliations
Review

GLP-1 single, dual, and triple receptor agonists for treating type 2 diabetes and obesity: a narrative review

Nasreen Alfaris et al. EClinicalMedicine. .

Abstract

Obesity and type 2 diabetes mellitus (T2DM) present major global health challenges, with an increasing prevalence worldwide. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have emerged as a pivotal treatment option for both conditions, demonstrating efficacy in blood glucose management, weight reduction, cardiovascular disease prevention, and kidney health improvement. GLP-1, an incretin hormone, plays a crucial role in glucose metabolism and appetite regulation, influencing insulin secretion, insulin sensitivity, and gastric emptying. The therapeutic use of GLP-1RAs has evolved significantly, offering various formulations that provide different efficacy, routes of administration, and flexibility in dosing. These agents reduce HbA1c levels, facilitate weight loss, and exhibit cardiovascular protective effects, making them an integral component of T2DM and obesity management. This review will discuss the currently approved medication for T2DM and obesity, and will also highlight the advent of novel agents which are dual and triple hormonal agonists which represent the future direction of incretin-based therapy.

Funding: National Institutes of HealthNIDDKU24 DK132733 (FCS), UE5 DK137285 (FCS), and P30 DK040561 (FCS).

Keywords: Energy expenditure; GLP-1/Glucagon dual agonists; GLP-1RA; GLP1/GIP dual agonists; GLP1/GIP/Glucagon triple agonists; Incretin therapy; Insulin secretion; Metabolism; Obesity; Pharmacotherapy for obesity; Type 2 diabetes; Weight management.

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Conflict of interest statement

F.C.S reports grants from the NIH NDDK, she also reports personal consulting fees from Eli Lilly, Novo Nordisk, Boehringer Ingelheim, Pfizer, Rhythm, Currax, and Gelesis. F.C.S also serves on the board of directors of The Obesity Society, she also serves as an obesity section member of the American Heart Association and the American Academy of Pediatrics. Finally, she heads the obesity section at the American Medical Woman’s Association. N.A. reports receiving personal consulting fees from Eli Lilly and Novo Nordisk. And serves on advisory board for Eli Lilly and receiving travel support from Novo Nordisk. K.K. reports research grants (HRSA T32HP32715 (July 2020–June 2022)). V.R.J reports consulting fees from Novo Nordisk and receiving honoraria for lectures given for Eli Lilly and educational institutes. None is related to the work presented herein. All other authors declare no conflict of interest.

Figures

Fig. 1
Fig. 1
Weight loss with retatrutide1, tirazepatide2, and semaglutide3 compared to placebo.
Fig. 2
Fig. 2
Change in quality adjusted life years with use of GLP-1Ras compared to No treatment.
Fig. 3
Fig. 3
A: Cost savings with use of endoscopic sleeve gastroplasty vs. semaglutide over 5 years. B: Quality adjusted life years according to use of endoscopic sleeve gastroplasty vs. subcutaneous semaglutide 2.4 mg for weight loss at different time points.
Fig. 4
Fig. 4
Suggested treatment algorithm for the choice of GLP1-RA, dual, and triple agonists in the treatment of obesity.
See this image and copyright information in PMC

References

    1. Ong K.L., Stafford L.K., McLaughlin S.A., et al. Global, regional, and national burden of diabetes from 1990 to 2021, with projections of prevalence to 2050: a systematic analysis for the Global Burden of Disease Study 2021. Lancet. 2023;402(10397):203–234. - PMC - PubMed
    1. Alfaris N., Alqahtani A.M., Alamuddin N., Rigas G. Global impact of obesity. Gastroenterol Clin. 2023;52(2):277–293. - PubMed
    1. https://www.who.int/news/item/04-03-2022-world-obesity-day-2022-accelera...
    1. Sattar N., Lee M.M., Kristensen S.L., et al. Cardiovascular, mortality, and kidney outcomes with GLP-1 receptor agonists in patients with type 2 diabetes: a systematic review and meta-analysis of randomised trials. Lancet Diabetes Endocrinol. 2021;9(10):653–662. - PubMed
    1. Egan J.M. Physiological integration of taste and metabolism. N Engl J Med. 2024;390(18):1699–1710. - PubMed

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