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

Obesity represents a global health challenge, with a critical and urgent need for long-term, sustainable management strategies. Tirzepatide is a novel dual glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptor agonist. At first approved for the treatment of type 2 diabetes mellitus, tirzepatide represents one of the latest clinically approved and commercially available pharmacological options for obesity management. This narrative review aimed to synthesize existing clinical evidence on the efficacy and safety of tirzepatide in non-diabetic obese individuals. A comprehensive literature search was conducted using the PubMed, Scopus, Web of Science, ClinicalTrials.gov, and Google Scholar databases to identify relevant clinical trials, meta-analyses, and original studies assessing the weight-loss impact of tirzepatide from 2022 onwards. Synthesized evidence indicated 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, waist circumference, blood pressure, and atherosclerotic cardiovascular disease risk. Health-related quality of life 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.