Exploring the Efficacy and Safety of Tirzepatide in Obesity Management and Cardiometabolic Risk Factors: A Comprehensive Systematic Review and Meta‐Analysis

The global prevalence of obesity and its related complications continue to rise, emphasising the need for effective treatment strategies. Tirzepatide, a novel glucagon-like peptide-1/glucose-dependent insulinotropic polypeptide dual agonist, has emerged as a promising pharmacological option in obesity management due to its potential in weight reduction and cardiometabolic improvement. We conducted a systematic review and meta-analysis following PRISMA guidelines, including randomised controlled trials (RCTs) comparing the efficacy and safety of Tirzepatide with placebo in adults with obesity, with or without type 2 diabetes. We searched PubMed, Cochrane Library, and EMBASE databases up to December 15, 2024. Ten RCTs were included, comprising 6257 participants. Tirzepatide significantly reduced body weight compared to placebo, with a total pooled mean difference of -11.62 kg (95% confidence interval: -14.24 to -9.01, p < 0.001). In the highest dosage group of 15 mg, 88.1%, 63.3%, and 51.8% of participants achieved weight reductions exceeding 5%, 10%, and 15% respectively. Significant improvements were also noted in cardiometabolic risk factors, including haemoglobin A1C, waist circumference, body mass index, and lipid profiles. Tirzepatide showed a favourable safety profile, without increasing the risk of serious adverse events or impacting mortality rates. Tirzepatide has demonstrated effectiveness in achieving significant weight loss and enhancing cardiometabolic health in adults with obesity. While it maintains a favourable safety profile, further studies are essential to investigate its long-term safety and determine the optimal duration of treatment.