Improvements in Cardiometabolic Risk Factors by Weight Reduction: A Post Hoc Analysis of Adults With Obesity Randomly Assigned to Tirzepatide

BACKGROUND: Tirzepatide reduced weight and improved cardiometabolic risk factors for participants in the SURMOUNT-1 trial. The changes in cardiometabolic risk factors by degree of tirzepatide-induced weight reduction across a wide spectrum of weight loss have not been reported. OBJECTIVE: To determine changes in cardiometabolic risk factors by weight reduction. DESIGN: Post hoc analysis of the phase 3, randomized, double-blind, SURMOUNT-1 trial (ClinicalTrials.gov: NCT04184622). SETTING: 119 sites in 9 countries. PARTICIPANTS: = 1605) with obesity, or overweight with weight-related complications (excluding diabetes), randomly assigned to tirzepatide treatment groups. INTERVENTION: Once-weekly tirzepatide, 5, 10, or 15 mg. MEASUREMENTS: Changes from baseline to week 72 in cardiometabolic risk factors by weight reduction. RESULTS: were observed even with modest weight reduction, with the steepest effect occurring between less than 5% and less than 20% weight reduction. Improvements in levels of triglycerides, high-density lipoprotein (HDL) cholesterol, low-density lipoprotein cholesterol, and non-HDL cholesterol were primarily observed only after weight reductions greater than 10%. Results were consistent after adjustment for baseline differences. LIMITATIONS: The analysis was post hoc and should be regarded as hypothesis-generating. Duration and sample size precluded evaluation of cardiovascular outcomes. CONCLUSION: In SURMOUNT-1, tirzepatide-associated improvements in cardiometabolic risk factors positively related to the degree of weight reduction, but the pattern varied depending on outcome measure. PRIMARY FUNDING SOURCE: Eli Lilly and Company.