Tirzepatide significantly reduces body weight, waist circumference, blood pressure, and lipids in obese non-diabetic adults

Obesity is a chronic disease that significantly increases the risk of developing hypertension, dyslipidemia, insulin resistance, systemic inflammation, heart failure, and atherosclerotic cardiovascular disease (ASCVD). Current standard-of-care often falls short in achieving sustained weight loss and comprehensive cardiometabolic improvements. Tirzepatide, a dual agonist of the glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptors, has demonstrated substantial weight loss and metabolic benefits in various populations, but its combined cardiometabolic effects specifically in non-diabetic adults with obesity or overweight required a comprehensive evaluation.

This systematic review and meta-analysis evaluated the cardiometabolic effects of tirzepatide in adults with obesity or who were overweight and had no diabetes. Data were systematically extracted from four randomized controlled trials (RCTs) identified through a comprehensive search. Primary endpoints included percentage weight change, percentage change in waist circumference, percentage change in systolic and diastolic blood pressure, and reductions in triglycerides, LDL cholesterol, and HDL cholesterol. Cardiometabolic effects were analyzed using a random-effects generic inverse-variance model, comparing tirzepatide against placebo. Cardiovascular outcomes related to heart failure with preserved ejection fraction and ASCVD populations were narratively assessed.

The meta-analysis revealed that tirzepatide significantly reduced body weight compared to placebo. The overall estimate for weight loss was a mean difference (MD) of -18.42% (95% CI, -22.05 to -14.79; I² = 70.9%). Even after omitting a randomized-withdrawal study, the effect remained substantial (MD = -18.01%, 95% CI, -24.86 to -11.16; I² = 77.6%). A highly statistically significant reduction in waist circumference was also observed:

Tirzepatide reduced waist circumference by -15.20 cm (95% CI, -17.69 to -12.70; I² = 23.5%). Additionally, tirzepatide demonstrated significant improvements in both systolic and diastolic blood pressure, as well as favorable changes in lipid profiles, including reductions in triglycerides and LDL cholesterol, and increases in HDL cholesterol. These findings extend previous research on tirzepatide in T2D patients, confirming its broad cardiometabolic benefits in a non-diabetic obese population.