Improvements in Cardiometabolic Risk Factors by Weight Reduction: A Post Hoc Analysis of Adults With Obesity Randomly Assigned to Tirzepatide
Bruno Linetzky, Naveed Sattar, Subodh Verma, Harlan M. Krumholz, Cathy Chang Xie, Hunter T. Hoffmann, Sarah Zimner‐Rapuch, Amelia Torcello‐Gómez, Adam Stefański
Abstract
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.