Degree of Weight Loss Affects Tirzepatide-Linked Cardiometabolic Risk Improvement
TUESDAY, July 1, 2025 -- For adults with obesity or overweight, tirzepatide-linked improvements in cardiometabolic risk factors are associated with the degree of weight reduction, according to a study published online June 24 in the Annals of Internal Medicine.
Bruno Linetzky, M.D., Ph.D., from Eli Lilly and Company in Indianapolis, and colleagues examined changes in cardiometabolic risk factors by degree of weight reduction in a post-hoc analysis of a phase 3 trial involving 1,605 adults with obesity or overweight with weight-related complications (excluding diabetes) who were randomly assigned to tirzepatide treatment groups (once-weekly 5, 10, or 15 mg).
The researchers found that participants who lost at least 35 percent of their body weight from baseline to week 72 had mean changes of up to –14.2 and –9.2 mm Hg for systolic and diastolic blood pressure, respectively, –32.4 cm for waist circumference, –59.7 percent for the homeostatic model assessment of insulin resistance (HOMA-IR), and –0.65 percentage point for hemoglobin A1c. For waist circumference and blood pressure, the relationship between percentage weight reduction and changes in cardiometabolic risk factors was mostly linear, with a steeper slope for systolic than diastolic blood pressure. Even with modest weight reduction, there were decreases in HOMA-IR and hemoglobin A1c, with the steepest effect between <5 percent and <20 percent weight reduction. Levels of triglycerides, high-density lipoprotein (HDL) cholesterol, low-density lipoprotein cholesterol, and non-HDL cholesterol improvements were mainly seen after weight reductions >10 percent.
"Understanding whether there are specific thresholds of weight reduction associated with minimum or maximum cardiometabolic benefits may assist clinicians in tailoring weight reduction goals to individual patients seeking to reduce their cardiometabolic risk," the authors write.
Several authors disclosed ties to relevant organizations, including Eli Lilly, the manufacturer of tirzepatide.
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