Ann Intern Med

Tirzepatide-driven weight loss yields graded improvements in cardiometabolic risk factors

June 26, 2025

Study details: This post hoc analysis evaluated data from adults with obesity (n=1,605) who were randomized to once-weekly tirzepatide (5, 10, or 15 mg) or placebo in the SURMOUNT-1 trial (NCT04184622). Researchers assessed whether cardiometabolic improvements were attributable to weight loss itself or to direct drug effects.

Results: Participants (mean age, 45 years; BMI, 38 kg/m²; 68% female) who lost ≥35% of body weight experienced substantial improvements:

• Systolic BP: -14.2 mm Hg (95% confidence interval [CI], -16.1 to -12.3 mm Hg)
• Diastolic BP: -9.2 mm Hg (CI, -10.6 to -7.8 mm Hg)
• Waist circumference: -32.4 cm (CI, -33.5 to -31.3 cm)
• Homeostatic model assessment of insulin resistance (HOMA-IR): -59.7% (CI, -63.6% to -55.3%)
• HbA1c: -0.65 percentage points (CI, -0.70 to -0.61 percentage point).

The relationship between weight loss and cardiometabolic improvements was largely linear, with steeper effects for systolic BP. Notably, insulin sensitivity and glycemic control improved even with modest weight loss, while lipid improvements were more pronounced after >10% weight reduction.

Clinical impact: For patients with obesity, cardiometabolic improvements with tirzepatide tracked with weight loss magnitude, though response patterns varied by outcome.

Source:

Linetzky B, et al. (2025, June 24). Ann Intern Med. Improvements in Cardiometabolic Risk Factors by Weight Reduction: A Post Hoc Analysis of Adults With Obesity Randomly Assigned to Tirzepatide. https://pubmed.ncbi.nlm.nih.gov/40550133/