Pharmacogenomics of GLP-1 Receptor Agonists: Precision Medicine in the Age of Ozempic and Mounjaro

Glucagon-like peptide-1 (GLP-1) receptor agonists — including semaglutide (Ozempic®, Wegovy®) and the dual GIP/GLP-1 agonist tirzepatide (Mounjaro®, Zepbound®) — have transformed the management of type 2 diabetes, obesity, and cardiovascular disease. Yet a clinically significant and underappreciated challenge persists: profound inter-individual variability in both efficacy and tolerability. Some patients lose more than 20% of body weight; others less than 5%. Some experience debilitating nausea; others experience none at all.This narrative review synthesises the rapidly evolving evidence in pharmacogenomics as it applies to GLP-1 therapies, with a focus on: (1) the genetic architecture of drug-response variability across GLP1R, GIPR, ARRB1, TCF7L2, MC4R, and related loci; (2) landmark genomic research including the April 2026 23andMe GWAS published in Nature (n=27,885) — the largest pharmacogenomic study of GLP-1 drugs to date; (3) the strategic positioning of leading biopharma companies (Novo Nordisk, Eli Lilly, 23andMe Research Institute, PGxAI) in this space; (4) the emerging research landscape in India and South Asia, where the world's largest diabetes burden intersects with a distinct and undercharacterised pharmacogenomic profile; and (5) a roadmap toward clinically actionable precision prescribing. We argue that GLP-1 pharmacogenomics has moved from exploratory science to actionable discovery, and that its translation into clinical practice — particularly for the 1.3 billion people of South Asia — is the defining precision medicine challenge of the next decade in metabolic disease.