Retatrutide, a hormone receptor agonist targeting glucagon, glucagon-like peptide 1, and glucose-dependent insulinotropic polypeptide, is being developed to treat obesity. A literature review from April 2019 to April 2024 included such terms as “retatrutide,” “LY3437943,” “overweight,” and “obesity.” Phase I proof-of-concept studies led to phase II trials showing up to 24% body weight reduction and nearly 20 cm waist circumference reduction. The most common adverse effects were gastrointestinal. Ongoing phase II and III studies aim to further evaluate the safety and efficacy of retatrutide as a novel triagonist for obesity treatment.
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UrvaSCoskunTLohMT, et alLY3437943, a novel triple GIP, GLP-1, and glucagon receptor agonist in people with type 2 diabetes: a phase 1b, multicentre, double-blind, placebo-controlled, randomized, multiple-ascending dose trial. Lancet. 2022;400(10366):1869-1881. https://doi.org/10.1016/S0140-6736(22)02033-5
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FukudaM.The role of GIP receptor in the CNS for the pathogenesis of obesity. Diabetes. 2021;70(9):1929-1937. https://doi.org/10.2337/dbi21-0001
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AdriaenssensAEBiggsEKDarwishT, et alGlucose-dependent insulinotropic polypeptide receptor-expressing cells in the hypothalamus regulate food intake. Cell Metab. 2019;30(5):987-996.e6. https://doi.org/10.1016/j.cmet.2019.07.013
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JastreboffAMKaplanLMFríasJP, et alTriple-hormone-receptor agonist retatrutide for obesity—a phase 2 trial. N Engl J Med. 2023;389(6):514-526. https://doi.org/10.1056/NEJMoa2301972
Eli Lilly and Company. A study of retatrutide (LY3437943) on renal function in participants with overweight or obesity and chronic kidney disease with or without type 2 diabetes. (Clinicaltrials.gov identifier NCT05936151) Published 2023. Accessed April 24, 2024. https://classic.clinicaltrials.gov/ct2/show/NCT05936151
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Eli Lilly and Company. A study of retatrutide (LY3437943) in participants who have obesity or overweight (TRIUMPH-1). (Clinicaltrials.gov identifier NCT05929066) Published 2023. Accessed April 24, 2024. https://classic.clinicaltrials.gov/ct2/show/NCT05929066
13.
Eli Lilly and Company. A study of retatrutide (LY3437943) in participants with type 2 diabetes mellitus who have obesity or overweight (TRIUMPH-2). (Clinicaltrials.gov identifier NCT05929079) Published 2023. Accessed April 24, 2024. https://classic.clinicaltrials.gov/ct2/show/NCT05929079
14.
Eli Lilly and Company. A study of retatrutide (LY3437943) in participants with obesity and cardiovascular disease (TRIUMPH-3). (Clinicaltrials.gov identifier NCT05882045) Published 2023. Accessed April 24, 2024. https://classic.clinicaltrials.gov/ct2/show/NCT05882045
15.
Eli Lilly and Company. A study of retatrutide (LY3437943) once weekly in participants who have obesity or overweight and osteoarthritis of the knee (TRIUMPH-4). (Clinicaltrials.gov identifier NCT05931367) Published 2023. Accessed April 24, 2024. https://classic.clinicaltrials.gov/ct2/show/NCT05931367
16.
Eli Lilly and Company. The effect of retatrutide once weekly on cardiovascular outcomes and renal function in adults living with obesity (TRIUMPH-OUTCOMES). (Clinicaltrials.gov identifier NCT06383390) Published 2024. Accessed April 24, 2024. https://classic.clinicaltrials.gov/ct2/show/NCT06383390
PasternakBWintzellVHviidA, et alGlucagon-like peptide 1 receptor agonist use and risk of thyroid cancer: Scandinavian cohort study. BMJ. 2024;385:e078225. https://doi.org/10.1136/bmj-2023-078225
