Abstract 4343615: Improvements in Cardiometabolic Risk Factors by Body Weight Reduction with Tirzepatide in Adults with Obesity and Prediabetes: A Post Hoc Analysis of the 3-year SURMOUNT-1 study

Background: In the 3-year SURMOUNT-1 study in people with obesity and prediabetes, tirzepatide treatment was associated with significant and consistent body weight reduction, lower risk of progression to type 2 diabetes, and significant improvement in cardiometabolic risk factors compared with placebo. This post hoc analysis assessed changes in cardiometabolic risk factors by body weight reduction thresholds with tirzepatide. Methods: Participants (N=458) randomized to receive tirzepatide (pooled 5/10/15 mg doses) and with an on-treatment body weight measurement at Week 176 were included in the analysis. The proportion of participants achieving body weight reduction thresholds (<5%, 5 to <10%, 10 to <15%, 15 to <20%, 20 to <25%, 25 to <30%, 30 to <35%, and ≥35%) at Week 176 and change from baseline at Week 176 in cardiometabolic risk factors, including blood pressure, lipid profile, and glycemic parameters, by body weight reduction thresholds were assessed. Results: At baseline, mean waist circumference was 116.5 cm, systolic blood pressure: 126.1 mmHg, diastolic blood pressure: 80.4 mmHg, triglycerides: 153.1 mg/dL, HDL-C: 48.6 mg/dL, non-HDL-C: 141.6 mg/dL, LDL-C: 111.8 mg/dL, and HOMA-2-IR (computed with insulin): 2.1. Improvements in waist circumference (3.2-35.3 cm reduction), HbA1c (0.30-0.76% reduction) and triglycerides (15-48% reduction) were observed among all body weight reduction subgroups (Table). HOMA2-IR, blood pressure and HDL-C, non-HDL-C and LDL-C also improved among participants who lost ≥5% of body weight. Overall, greater improvements in cardiometabolic risk factors were generally associated with greater body weight reduction. Conclusions: In this post hoc analysis of the 3-year SURMOUNT-1 study, tirzepatide treatment was associated with improved cardiometabolic risk factors, that were generally greater in magnitude with higher degrees of body weight reduction among people with obesity and prediabetes.