Background: The effect of tirzepatide (TZP) on the risk of developing type 2 diabetes (T2D) in people with obesity or overweight is unknown. We aimed to assess the impact of TZP treatment on T2D risk in the Phase 3 SURMOUNT-1 trial through predictive modelling.

Methods: Cardiometabolic Disease Staging, a validated robust tool providing 10-year risk estimates of T2D, was applied to the SURMOUNT-1 trial to derive risk scores at baseline, 24, and 72 weeks. Mean risk scores and change from baseline to week 72 were calculated from a mixed model.

Results: A total of 2539 participants were randomized 1:1:1:1 to TZP 5/10/15 mg and placebo (PBO) (mean age=45 years; female=68%; White=71%). Mean risk scores at baseline ranged from 23-24% and did not differ between groups. Mean risk scores for TZP 5, 10, 15 mg, and PBO groups were 13%, 11%, 11%, and 21% at week 24 and 11%, 9%, 9%, and 23% at week 72, respectively. At week 72, the absolute mean risk reductions from baseline were 12%, 14%, 15%, and 1% for TZP 5 mg, 10 mg, 15 mg, and PBO groups, corresponding to median relative risk reductions of -60.3%, -68.3%, -69%, and -10.8%, respectively. This resulted in significantly greater risk reduction between TZP groups vs. PBO (5 mg: 12%, 10 mg: 14%, 15 mg: 14%; p<0.001).

Conclusion: Treatment with TZP significantly reduced the 10-year predicted risk of developing T2D compared to PBO; most of the reduction in predicted risk was achieved by week 24.

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Disclosure

E. R. Hankosky: Employee; Eli Lilly and Company, Other Relationship; Eli Lilly and Company. H. Wang: None. L. M. Neff: Employee; Eli Lilly and Company, Research Support; Aegerion Pharmaceuticals, Stock/Shareholder; Eli Lilly and Company. H. Kan: Employee; Eli Lilly and Company, Stock/Shareholder; Eli Lilly and Company. F. Wang: None. N. Ahmad: Employee; Eli Lilly and Company. A. Stefanski: Employee; Eli Lilly and Company. W. Garvey: Advisory Panel; Boehringer-Ingelheim, Novo Nordisk, Eli Lilly and Company, Merck & Co., Inc., Alnylam Pharmaceuticals, Inc., Fractyl Health, Inc., Inogen, Research Support; Novo Nordisk, Eli Lilly and Company, Epitomee, Pfizer Inc., Neurovalens.

Funding

Eli Lilly and Company

© 2023 by the American Diabetes Association
2023
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