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Additional analyses were conducted at individual study level or pooled across 5 SURPASS trials

The 2025 Cell Metabolism study found that tirzepatide did not significantly worsen metabolic adaptation in human participants

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Findings: RCTSURMOUNT-2 trial - Tirzepatide vs Placebo for Weight Loss in Diabetes, Lancet (2023) [PubMed abstract] Design: Randomized, placebo-controlled trial (N=938 | length = 72 weeks) in overweight diabetics (mean BMI 36 | mean A1C 8.02%) Treatment: Tirzepatide 10 mg once weekly vs Tirzepatide 15 mg once weekly vs Placebo Primary outcome: Coprimary endpoints were the percent change in body weight from baseline and body weight reduction of 5% or higher Results: Primary outcome (% reduction in weight): Tirzepatide 10 mg - 12.8%, Tirzepatide 15 mg - 14.7%, Placebo - 3.2% (p 35 - 68.9% Randomized treatment groups Group 1 (374 patients): Tirzepatide titrated to the maximum tolerated dose of 10 mg or 15 mg once weekly Group 2 (376 patients): Semaglutide titrated to the maximum tolerated dose of 1.7 mg or 2.4 mg once weekly Tirzepatide was initiated at a dose of 2.5 mg once weekly, and the dose was increased by 2.5 mg every 4 weeks until a maximum tolerated dose of 10 mg or 15 mg was reached