# Who Wins the Battle Against Obesity? A Network Meta‐Analysis Comparing Tirzepatide and Semaglutide

## TL;DR

Tirzepatide is more effective than semaglutide in reducing body weight and improving blood sugar levels in people with obesity.

## Contribution

This study provides a network meta-analysis comparing the efficacy of tirzepatide and semaglutide for obesity treatment.

## Key findings

- Tirzepatide showed greater weight reduction than semaglutide in percentage and absolute kilograms.
- Tirzepatide led to more significant reductions in BMI and waist circumference compared to semaglutide.
- Tirzepatide improved glycemic parameters more effectively than semaglutide, reducing HbA1c and fasting blood glucose.

## Abstract

Pharmacological therapies are recommended for individuals with obesity. Semaglutide, a glucagon‐like peptide‐1 receptor agonist (GLP‐1), and tirzepatide, a dual glucose‐dependent insulinotropic polypeptide and GLP‐1 receptor agonist (GIP/GLP‐1), are among the leading pharmacological options for obesity treatment. This network meta‐analysis (NMA) aims to evaluate the comparative efficacy of these two agents in reducing body weight and improving glycemic parameters.

Pairwise comparisons within the NMA were conducted using a frequentist approach in RCTs comparing tirzepatide or semaglutide versus placebo, as well as tirzepatide versus semaglutide at their maximum dosages (15 and 2.4 mg, respectively).

A total of 28 RCTs were included, comprising 34 367 participants, 39.6% of whom were women and with a mean age of 57.8 ± 8.95 years. Tirzepatide demonstrated superiority over semaglutide in percentage weight reduction (mean difference [MD] 6.10%; 95% CI: 3.64, 8.57), absolute weight loss (MD 4.55 kg; 95% CI: 1.28, 7.83), BMI reduction (MD 1.71 kg/m2; 95% CI: 0.08, 3.34), and waist circumference reduction (MD 2.89 cm; 95% CI: 1.25, 4.53). Regarding glycemic parameters, tirzepatide was also more effective than semaglutide in reducing HbA1c (MD 0.33%; 95% CI: 0.20, 0.46) and fasting blood glucose (MD 10.39 mg/dL; 95% CI: 4.48, 16.29).

In this NMA, tirzepatide appeared to be superior to semaglutide in both body weight reduction and improvement of glycemic indices.

Tirzepatide demonstrated greater effectiveness in reducing body weight compared to semaglutide and placebo, both in percentage and absolute kilograms, and also led to more pronounced reductions in BMI and waist circumference.

Beyond weight loss, tirzepatide was superior to semaglutide in improving glycemic parameters, achieving greater reductions in HbA1c and fasting blood glucose in individuals with overweight or obesity.

Network meta‐analysis comparing the effects of tirzepatide, semaglutide, and placebo on body weight reduction and glycemic outcomes in adults with overweight or obesity.