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August 15, 2026CureusOpen Access

Comparative Efficacy and Safety of Tirzepatide Versus Semaglutide for Obesity: A Systematic Review

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Authors

SASamih Abdelmutalab Mohamed AbdallaLGLima GharbawiPortsmouth Hospitals NHS TrustNENamaa Elshaikh

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Implication

Systematic review demonstrates superior weight reduction with tirzepatide over semaglutide in adults with obesity, indicating enhanced metabolic benefits from dual-receptor agonism.

Key Points

  • To systematically identify, appraise, and synthesize original comparative studies evaluating the efficacy and safety of tirzepatide versus semaglutide in adults with overweight or obesity.
  • Conducted a PRISMA-compliant search across PubMed/MEDLINE, Embase, Scopus, and Web of Science up to 20 July 2026, using RoB 2 and ROBINS-I tools for risk-of-bias assessment.
  • Identified 11 comparative studies comprising approximately 62,700 analyzed participants across one phase 3b open-label randomized active-controlled trial and 10 retrospective observational cohorts from multiple countries.
  • In the randomized trial, mean weight change at 72 weeks was -20.2% with tirzepatide versus -13.7% with semaglutide.
  • In real-world cohorts, adjusted between-group differences in weight loss ranged from approximately 2.3 to 4.4 percentage points favoring tirzepatide, with greater improvements in blood pressure and glycated hemoglobin.
  • Both medications exhibited broadly comparable short-term safety profiles, with gastrointestinal adverse events predominating for both agents.

Cite This Study

Abdalla et al. (2026) studied this question.

synapsesocial.com/papers/6a801a2875c2e31742c86a2dhttps://doi.org/10.7759/cureus.114454
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Also Consider

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  1. 1Worldwide trends in underweight and obesity from 1990 to 2022: a pooled analysis of 3663 population-representative studies with 222 million children, adolescents, and adults2024 · 2,443 citations
  2. 2Real-World Weight Loss Observed With Semaglutide and Tirzepatide in Patients with Overweight or Obesity and Without Type 2 Diabetes (SHAPE)2025 · 20 citations
  3. 3Real-World Effectiveness and Safety of Tirzepatide, Semaglutide, and Liraglutide in Adults with Overweight or Obesity without Diabetes: A Comparative Study2026 · 2 citations
  4. 4Cardiovascular outcomes of semaglutide and tirzepatide for patients with type 2 diabetes in clinical practice2025 · 41 citations
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