BMI shift and associated cardiometabolic risk factors in people with type 2 diabetes and obesity and/or overweight: a post hoc analysis from SURMOUNT-2

Abstract In SURMOUNT-2 (SM-2), treatment with once weekly GIP and GLP-1 receptor agonist tirzepatide (TZP) resulted in superior body weight reductions relative to placebo in people living with obesity and T2D. This post hoc analysis assessed whether participants with obesity (body mass index [BMI] ≥30 kg/m2) or overweight (BMI ≥27 kg/m2 with at least one weight-related comorbid condition) who shifted to a lower BMI category had improved cardiometabolic factors. Change in BMI category (<25 kg/m2, 25 to <30 kg/m2, 30 to <35 kg/m2, 35 to <40 kg/m2, and ≥40 kg/m2) from baseline to week 72 was assessed in participants from SM-2 treated with TZP 10 or 15 mg (N=623) or placebo (PBO)(N=315). BMI shifts were grouped into "improved" (shift to lower BMI category) or "non-improved" (stable or shift to a higher BMI category). Cardiometabolic parameters examined included waist circumference, fasting insulin, fasting glucose, HbA1c, blood pressure, and lipid profile. A mixed model with repeated measures was performed to estimate the mean change from baseline to week 72 for these parameters. In this post hoc analysis a total of 484 (52.1%) participants had improved BMI at week 72. For those whose BMI did not improve, most had stable BMI and only 11 (1.2%) had worsened BMI. Nine participants had no post-baseline BMI measurements and were excluded from analysis. Most participants demonstrated improved BMI with TZP treatment (N=418, 67%) vs PBO (N=66, 21%)(Table). Furthermore, 21% (N=129) of participants on TZP improved by ≥2 BMI categories compared to only 1 participant with PBO. Compared to those with non-improved BMI, participants with improved BMI demonstrated greater improvement in cardiometabolic risk factors, including decreases from baseline in waist circumference, fasting insulin, fasting glucose, HbA1c, systolic and diastolic blood pressure, triglycerides, and cholesterol (non-HDL-c, and LDL-c) and increases from baseline in HDL-c (Figure). Greater improvements to cardiometabolic risk factors were seen in participants on TZP vs PBO. Shifts to lower BMI categories were greater among TZP-treated people living with obesity or overweight and T2D in SM-2 and were associated with improved cardiometabolic risk factors, in this post hoc analysis. SURMOUNT-mortality and morbidity and cardiovascular outcome trials are ongoing to examine the impact of TZP treatment on CVD and mortality.