Tirzepatide and Obesity: A Narrative Review

Abstract This research systematically evaluates the efficacy and safety of Tirzepatide (TZP), a novel dual agonist of the glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 (GLP-1) receptors, in treating obesity and diabetes with implications for global health. A comprehensive electronic literature search was conducted across databases including Google Scholar, PubMed, Scopus and Web of Science. Keywords included ‘Tirzepatide’, AND ‘Excess Fat Accumulation’, AND ‘Non-Alcoholic Fatty Liver Disease’, AND ‘Insulin Resistance’, AND ‘Type 2 Diabetes Mellitus’, AND ‘Morbidity’, AND ‘Mortality’, ‘GIP’, AND ‘GLP-1, Glucose-Dependent Insulinotropic Polypeptide’, AND ‘Glucagon-Like Peptide-1’, AND ‘Obesity Pharmacotherapy’, AND ‘Weight Loss’, AND ‘Glycemic control’, AND ‘Weight loss’, AND ‘Weight loss maintenance’, AND ‘Satiety’, AND ‘Adverse effects’ in combination with Boolean operators. The retrieved studies, including randomised controlled trials, report that TZP significantly reduces body weight, body mass index and waist circumference in obese patients with or without type2 diabetes (T2DM). Its dose-dependent effect correlates with improvements in metabolic parameters, including glycaemic control (glycated haemoglobin reduction), insulin sensitivity and lipid profiles. TZP’s efficacy in weight loss surpasses that of GLP-1 receptor agonists alone, offering potential cardiovascular benefits and better metabolic health outcomes. Some evidence also suggests alterations in thyroid function tests during TZP treatment, underscoring the need to monitor thyroid-stimulating hormone (TSH) levels to avoid iatrogenic thyroid dysfunction. TZP’s role in managing metabolically healthy obesity and reducing progression to metabolically unhealthy states holds promise for enhancing global metabolic health. The drug’s dual mechanism slows gastric emptying and modulates gastrointestinal motility, thereby contributing to its potent weight-reducing effects. Overall, TZP represents a significant advancement in the pharmacotherapy of obesity and diabetes, with broader implications for public health worldwide. However, further studies are needed to assess long-term safety and thyroid-related outcomes.