W. Timothy Garvey

Aim We assessed the impact of tirzepatide on 10‐year predicted risk of developing type 2 diabetes (T2D) among participants in the SURMOUNT‐1 trial. Materials and Methods In this post hoc analysis of SURMOUNT‐1, the Cardiometabolic Disease Staging risk engine was used to calculate the 10‐year predicted risk of T2D at baseline, week 24 and week 72 among participants randomized to receive 5, 10, or 15 mg tirzepatide or placebo. Mean changes in risk scores from baseline to weeks 24 and 72 were compared between tirzepatide and placebo groups. Subgroup analyses were conducted based on participants' glycaemic status and body mass index at baseline. Results Mean baseline T2D predicted risk scores did not differ between tirzepatide and placebo groups (range: 22.9%‐24.3%). At week 72, mean absolute T2D predicted risk score reductions were significantly greater in tirzepatide groups (5 mg, 12.4%; 10 mg, 14.4%; 15 mg, 14.7%) versus placebo (0.7%). At week 72, median relative predicted risk reductions following tirzepatide treatment ranged from 60.3% to 69.0%. For participants with and without prediabetes, risk reductions were significantly greater in tirzepatide groups versus placebo. At week 72, participants with prediabetes (range: 16.0%‐20.3%) had greater mean risk score reductions from baseline versus those without prediabetes (range: 10.1%‐11.3%). Across body mass index subgroups, mean reductions from baseline were significantly greater in tirzepatide groups versus placebo. Conclusion Tirzepatide treatment significantly reduced the 10‐year predicted risk of developing T2D compared with placebo in participants with obesity or overweight, regardless of baseline glycaemic status.