Efficacy and safety of tirzepatide in people with type 2 diabetes by baseline body mass index: An exploratory subgroup analysis of SURPASS-AP-Combo

Aims: To assess the efficacy and safety of tirzepatide versus insulin glargine in people with type 2 diabetes (T2D) by baseline body mass index (BMI). Materials and Methods: Participants with T2D from the Phase 3 SURPASS-AP-Combo trial (NCT04093752) were categorized into three BMI subgroups (normal weight [<25 kg/m(2)], overweight [>= 25 and <30 kg/m(2)], and obese [>= 30 kg/m(2)]) according to World Health Organization criteria. Exploratory outcomes including glycaemic control, body weight, cardiometabolic risk, and safety were compared among three tirzepatide doses (5, 10 or 15 mg) and insulin glargine. Results: Of 907 participants, 235 (25.9%) had a BMI <25 kg/m(2), 458 (50.5%) a BMI >= 25 to <30 kg/m(2), and 214 (23.6%) a BMI >= 30 kg/m(2) at baseline. At Week 40, all tirzepatide doses led to a greater reduction in mean glycated haemoglobin (HbA1c; -2.0% to -2.8% vs. -0.8% to -1.0%, respectively) and percent change in body weight (-5.5% to -10.8% vs. 1.0% to 2.5%, respectively) versus insulin glargine, across the BMI subgroups. Compared with insulin glargine, a higher proportion of tirzepatide-treated participants achieved treatment goals for HbA1c and body weight reduction. Improvements in other cardiometabolic indicators were also observed with tirzepatide across all the BMI subgroups. The safety profile of tirzepatide was similar across all subgroups by BMI. The most frequent adverse events with tirzepatide were gastrointestinal-related events and decreased appetite, with relatively few events leading to treatment discontinuation. Conclusions: In participants with T2D, regardless of baseline BMI, treatment with tirzepatide resulted in statistically significant and clinically meaningful glycaemic reductions and body weight reductions compared with insulin glargine, with a safety profile consistent with previous reports.