Efficacy and Safety of Tirzepatide  for the Management of Obesity: A Systematic Review and Meta-analysis of Randomized  Controlled Trials (RCTs)

Objective: Obesity is a significant risk factor for Type 2 Diabetes and plays a significant role in global morbidity and mortality. While current pharmacological treatments, such as glucagon-like peptide-1 receptor agonists (GLP-1 RA), have demonstrated efficacy in weight loss and glycemic control, Tirzepatide, a dual glucose-dependent insulinotropic polypeptide, has arisen as a viable treatment option. This study aims to investigate the evidence on comparing Tirzepatide to placebo and GLP-1 RAs such as Semaglutide and Dulaglutide

Methods: We searched electronic databases to retrieve and include all randomized controlled trials (RCTs) that analyzed the effect of tirzepatide for the management of obesity. The revised Cochrane’s “Risk of Bias” tool for randomized trials (RoB 2.0) was used to assess the risk of bias in the included studies. Using RevMan, risk ratios (RR) along with the 95% confidence intervals (95% CI) were used for dichotomous outcomes, and standard mean differences (SMD) along with the 95% confidence intervals (95% CI) were used for continuous outcomes.

Results: A total of fourteen RCTs were included in our meta-analysis, reporting data from 9968 patients. When comparing tirzepatide to placebo, our analysis showed a statistically significant difference favoring Tirzepatide dosages of 5mg, 10mg and 15mg for change in mean body weight (SMD -2.25; 95% CI: -2.62 to -1.88), weight reduction of ≥ 5% (RR 3.76; 95% CI: 3.16-4.47), weight reduction of ≥ 10% (RR 6.40; 95% CI: 5.00-8.19) and weight reduction of ≥ 15% (RR 11.32; 95% CI: 8.34-15.37). When comparing Tirzepatide vs GLP-1 agonists, our meta-analysis showed a statistically significant difference favoring Tirzepatide dosages of 5mg, 10mg and 15mg for Change in mean body weight (SMD -2.18; 95% CI: -2.70 to -1.66), weight reduction of ≥ 5% (RR 2.96; 95% CI: 2.14-4.10), weight reduction of ≥ 10% (RR 3.25; 95% CI: 2.28-4.64), and weight reduction of ≥ 15% (RR 4.72; 95% CI: 2.75, 8.11).

Conclusion: This meta-analysis confirms that tirzepatide is an effective pharmacologic option for obesity treatment, demonstrating statistically significant reductions in mean body weight and BMI. Given its recent FDA approval for obesity, tirzepatide represents a promising advancement in obesity treatment, though further long-term studies are needed to assess sustained efficacy and long-term adverse effects.