Tirzepatide and Cardiometabolic Effects in Obese Non-diabetic Adults: A Systematic Review, Meta-Analysis, and Narrative Synthesis of Cardiovascular Outcomes

Obesity is a recurrent disease condition that predisposes individuals to an increased likelihood of developing hypertension, dyslipidemia, insulin resistance, systemic inflammation, heart failure, and atherosclerotic cardiovascular disease (ASCVD). Tirzepatide, a dual agonist of the glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 receptors, has been shown to produce clinically significant weight loss and metabolic improvements. However, the combined cardiometabolic effects of tirzepatide in adults with obesity or who are overweight and have no diabetes are not fully understood. In this systematic review and meta-analysis, the effects of tirzepatide were systematically evaluated using data from randomized controlled trials in adults with obesity or overweight without diabetes. The meta-analyzed body weight effects of tirzepatide included data from four clinical trials. Weight-loss measures assessed include 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. Cardiovascular outcomes based on heart failure with preserved ejection fraction and ASCVD populations were narratively assessed. According to the results of this analysis, the overall estimate for the tirzepatide effect size compared to placebo shows significant weight loss (MD = -18.42%; 95% CI, -22.05 to -14.79; I² = 70.9%). When omitting the randomized-withdrawal study, there was still a substantial effect (MD = -18.01%, 95% CI, -24.86 to -11.16; I² = 77.6%). A highly statistically significant reduction in waist circumference was also observed (MD = -15.20 cm; 95% CI, -17.69 to -12.70; I² = 23.5%). Additionally, significant improvements in blood pressure and lipid measures were shown by tirzepatide. It is worth mentioning that the effect sizes for blood pressure and lipids are less precise due to a smaller sample size. Overall, tirzepatide is effective in producing considerable improvements in body weight and waist circumference in adults with obesity or overweight without diabetes. However, evidence regarding hard cardiovascular outcomes in this population remains insufficient.