This study compared the 5-year risk of diabetes complications of tirzepatide (TZP) and semaglutide with insulin glargine in individuals with type 2 diabetes (T2Ds) , using the BRAVO diabetes model, which has been validated to have a high degree of accuracy. We used the BRAVO model to predict 5-year complications among users of TZP (5 mg, mg, or 15 mg) , semaglutide (1 mg) , and insulin glargine, based on short-tern efficacy data from the SURPASS-2 trial and SUSTAIN-4 trial, under two scenarios: the short-term drug efficacy lasted for 5 years (optimistic) , and the drug efficacy diminished in 5 years (conservative) . We found a 5-year risk reduction in major adverse cardiovascular events (MACE) (relative risk [RR] 63.7%, 95% CI: 61.4%-66.2%) with 15 mg TZP under an optimistic scenario, and MACE (RR 87.6%, 95% CI: 86.8%-88.6%) risk reduction with 15 mg TZP under a conservative scenario, when compared with insulin glargine (Figure) . Lower doses of TZP also had similar, albeit slightly smaller, benefits. The long-term use of TZP and semaglutide may lead to a substantial reduction in diabetes-related complications among individuals with T2Ds, compared to insulin. A high dose of TZP was also superior to semaglutide in this respect.

Disclosure

S.Niu: None. T.Jiao: None. Y.Guo: None. J.Bian: None. L.Shi: None. V.Fonseca: Consultant; Abbott, Asahi Kasei Corporation, Bayer AG, Novo Nordisk, Sanofi, Research Support; Fractyl Health, Inc., Jaguar Gene Therapy, Stock/Shareholder; Abbott, Amgen Inc., BRAVO4Health, Mellitus Health. H.Shao: Board Member; BRAVO4HEALTH, LLC.

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