Abstract

Background and aims: While GLP-1 and dual GIP/GLP-1 receptor agonists are proven in trials, their real-world application in the Middle East requires scrutiny. This systematic review and meta-analysis compares the real-world effectiveness and treatment persistence of Tirzepatide versus Semaglutide in Middle Eastern populations.
Methods: Following PRISMA guidelines (PROSPERO: CRD42026019344), we searched PubMed, Embase, and the Saudi Digital Library for real-world studies published between 2020 and February 2026. Studies were included if they reported HbA1c or weight loss outcomes in adults with T2DM or obesity strictly within the MENA region.
Results: Seven studies (n=12,450) were synthesized. In the Middle Eastern subgroup, Tirzepatide demonstrated a superior weight loss of 15.5% to 22.0% compared to 10.3% to 11.6% for Semaglutide (p < 0.001). However, the 6-month discontinuation rate reached 56.3%, significantly higher than clinical trial benchmarks.
Conclusions: Tirzepatide offers enhanced clinical efficacy in MENA populations; however, high discontinuation rates—driven by localized supply chain disruptions and titration challenges during fasting periods—require tailored clinical protocols to maintain long-term metabolic outcomes.

Key words: Tirzepatide; Semaglutide; Metabolic syndrome; Treatment persistence; Middle East; Systematic review