Efficacy of tirzepatide in people with young-onset type 2 diabetes in the SURPASS programme

Background and aims: Young-onset type 2 diabetes (T2D), defined as diagnosed before age 40, presents with a more aggressive disease course, faster beta-cell deterioration and reduced response to treatment compared to later-onset T2D. Tirzepatide is a once weekly GIP and GLP-1 receptor agonist recently approved for the treatment of T2D. Despite younger baseline age, participants with young-onset T2D in the SURPASS programme had an overall worse health status (e.g., longer duration of diabetes, worse glycaemic control, higher mean body weight and BMI, and a more atherosclerogenic lipid profile) compared to those with later-onset T2D. Here, we assessed the effect of tirzepatide on glycaemic control, body weight and cardiometabolic markers in participants with young-onset T2D from the SURPASS programme.

Materials and methods: This post hoc analysis compared changes in mean HbA1c, body weight, and cardiometabolic markers including waist circumference (WC), lipids, and blood pressure in participants with young-onset (N=873, 20.5%) vs later-onset T2D (N=3394, 79.5%) at Week 40 (SURPASS-1, -2, -5) or Week 52 (SURPASS-3). Analyses were done by study, based on data from participants while on assigned treatment without rescue medication (efficacy estimand). Mixed-model repeated measures (MMRM) were applied, adjusted for baseline values and study stratification factors, and the interaction between treatment and subgroup.

Results: No differential treatment effect was observed for participants with young- vs later-onset T2D. Tirzepatide treatment led to similar improvements in HbA1c and body weight in both subgroups at Week 40/52 for all tirzepatide doses (Figure). Furthermore, tirzepatide (all doses) improved waist circumference, lipids (triglycerides and HDL) and systolic blood pressure similarly between subgroups.

Conclusion: Tirzepatide treatment led to similar improvements in HbA1c, body weight and cardiometabolic markers, irrespective of age at T2D diagnosis. Future studies are warranted to evaluate whether an early intervention in young-onset T2D may provide opportunities to improve long-term outcomes.