Tirzepatide for Older Adults with Type 2 Diabetes and Without Obesity: A Post Hoc Analysis of the SURPASS Clinical Trials.

INTRODUCTION: Tirzepatide, a once-weekly glucose-dependent insulinotropic polypeptide/glucagon-like peptide-1 receptor agonist approved in the US for treating type 2 diabetes (T2D) and obesity, has demonstrated significant improvements in glycated hemoglobin A1c (HbA1c) and clinically meaningful weight loss in the SURPASS-1 to -5 clinical trials. This post hoc analysis examined the safety and efficacy results for tirzepatide in older participants with T2D who do not have obesity. METHODS: A post hoc analysis was conducted on a subgroup of participants aged ≥ 65 years with a body mass index (BMI) < 30 kg/mamongst the pooled SURPASS-1 through -5 clinical trial populations. Primary efficacy endpoints and safety were assessed for both this subgroup and overall pooled populations. RESULTS: Participants aged ≥ 65 years with BMI < 30 kg/mtreated with tirzepatide experienced clinically meaningful HbA1c reduction (- 1.97 to - 2.10%) regardless of the assigned randomized maintenance dose. In contrast, a dose-proportional HbA1c decrease was observed in the overall population. Weight reduction in this subgroup was dose-proportional but numerically lower than in the overall population. Older participants without obesity were more likely to discontinue treatment due to adverse events (AEs), although the overall incidence of AEs was low in this subgroup. The incidence of hypoglycemia in this group was consistent with that of the overall cohort, regardless of concurrent insulin or sulfonylurea use. CONCLUSIONS: Tirzepatide may be an effective treatment for older adults without obesity, and in this post hoc analysis, it was associated with clinically relevant HbA1c reduction and dose-proportional weight loss without increasing hypoglycemic risk.