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The emerging role of incretins and twincretins

In 2021, clinical trials reported the promising effects of incretins and a new class of dual glucagon-like peptide 1–glucose-dependent insulinotropic peptide receptor agonists in preventing and treating type 2 diabetes mellitus and obesity. These ‘twincretins’ will transform the prevention of obesity and type 2 diabetes mellitus and the care of people with these conditions.

Key advances

  • Once weekly semaglutide, the most potent GLP1 receptor agonist, was safe and effective for treating obesity, achieving average weight loss of 15% among individuals without any form of diabetes mellitus4.

  • In the SURPASS-1 trial, tirzepatide (a new dual GIP–GLP1 receptor agonist based on the native GIP sequence) was associated with up to 2% reduction in HbA1c and a dose-dependent reduction in body weight of 7–9 kg in patients with type 2 diabetes mellitus6.

  • Tirzepatide was superior to semaglutide in head-to-head comparisons in reducing HbA1c and body weight, with a similar incidence of gastrointestinal adverse effects7.

  • Tirzepatide was also superior to insulin degludec in reducing HbA1c and body weight, with a lower risk of hypoglycaemia8.

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Fig. 1: Weight loss with tirzepatide in phase III trials in patients with T2DM.


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Correspondence to Juliana C. N. Chan.

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Competing interests

J.C.N.C. has received speaker fees and research grants through institutions from Applied Therapeutics, Astra Zeneca, Bayer, Boehringer Ingelheim, Celltrion, Hua Medicine, Lee Powder, Lilly, Merck Sharpe Dohme, Merck Serono, Pfizer, Sanofi, Servier and Virtus Pharmaceutical. E.C. has received speaker fees from Sanofi, Novartis and institutional research support from Sanofi, Medtronic Diabetes and Powder Pharmaceuticals Inc.

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Chow, E., Chan, J.C.N. The emerging role of incretins and twincretins. Nat Rev Endocrinol 18, 73–74 (2022).

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