Efficacy and Safety of Tirzepatide for Weight Management in Non-Diabetic Obese ‎Individuals: A Narrative Review

Obesity remains a global health challenge, requiring long-term, sustainable treatment strategies. Tirzepatide, a dual glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptor agonist is the latest clinically approved and commercially available pharmacological option for obesity management, necessitating further research in non-diabetic individuals. This narrative review synthesizes existing clinical evidence on the efficacy and safety of Tirzepatide in non-diabetic obese individuals. A comprehensive literature search was conducted using PubMed, Scopus, Web of Science, ClinicalTrials.gov, and Google Scholar databases to identify relevant clinical trials, meta-analyses, and studies assessing its weight-loss impact from 2022 onwards. Synthesized evidence indicates that Tirzepatide achieved up to 20.9% weight loss over 72 weeks (SURMOUNT-1), 18.4% after lifestyle intervention (SURMOUNT-3), 17.5% in Chinese adults (SURMOUNT-CN), and 25.3% with continued treatment over 88 weeks (SURMOUNT-4). Meta-analyses confirmed higher odds of ≥5%-20% weight loss versus Semaglutide and Liraglutide, significantly reducing body mass index (BMI), waist circumference, blood pressure, and Atherosclerotic Cardiovascular Disease (ASCVD) risk. Health-related quality of life (HRQoL) improved with greater weight loss, and gastrointestinal side effects (nausea, diarrhea, constipation) were common but mild to moderate, with <5% treatment discontinuation. Tirzepatide achieved significant weight loss, cardiometabolic benefits, and improved quality of life in non-diabetic obese individuals, but further research is needed on long-term efficacy, safety, and clinical application.