{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T13:22:05Z","timestamp":1788355325212,"version":"build-2803163510"},"reference-count":113,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2025,8,25]],"date-time":"2025-08-25T00:00:00Z","timestamp":1756080000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Natural Science Foundation of China","award":["82170485"],"award-info":[{"award-number":["82170485"]}]},{"name":"Natural Science Foundation of China","award":["2023JJ30426"],"award-info":[{"award-number":["2023JJ30426"]}]},{"name":"Natural Science Foundation of Hunan Province","award":["82170485"],"award-info":[{"award-number":["82170485"]}]},{"name":"Natural Science Foundation of Hunan Province","award":["2023JJ30426"],"award-info":[{"award-number":["2023JJ30426"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Type 2 diabetes mellitus (T2DM) is frequently complicated by atherosclerosis (AS), with substantial overlap in their underlying pathophysiological mechanisms, posing serious threats to patient health. Tirzepatide, a novel dual agonist of glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptors, has demonstrated remarkable efficacy in glycemic control, weight reduction, and cardiometabolic improvement, making it a promising candidate for managing T2DM comorbid with AS. However, substantial interindividual variability in treatment response suggests a role for genetic determinants. This review systematically summarises current evidence on pharmacogenomic variants influencing the efficacy and toxicity of tirzepatide, explores the interplay between drug response genes and genetic susceptibilities to T2DM and AS, and highlights the potential of pharmacogenomics in guiding precision subtyping and individualised therapy. Finally, we highlight key challenges and future directions in the clinical translation of tirzepatide pharmacogenomics, aiming to inform personalized, genomics-guided therapy for cardiometabolic disease.<\/jats:p>","DOI":"10.3390\/ph18091261","type":"journal-article","created":{"date-parts":[[2025,8,26]],"date-time":"2025-08-26T06:25:57Z","timestamp":1756189557000},"page":"1261","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Pharmacogenomics of Tirzepatide: Genomic Insights into Dual GIP\/GLP-1 Agonist Response in Type 2 Diabetes and Atherosclerosis"],"prefix":"10.3390","volume":"18","author":[{"given":"Zihang","family":"Song","sequence":"first","affiliation":[{"name":"Key Laboratory of Model Animals and Stem Cell Biology in Hunan Province, Health Science Center, Hunan Normal University, Changsha 410013, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yifan","family":"Tang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Model Animals and Stem Cell Biology in Hunan Province, Health Science Center, Hunan Normal University, Changsha 410013, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mao","family":"Peng","sequence":"additional","affiliation":[{"name":"Key Laboratory of Model Animals and Stem Cell Biology in Hunan Province, Health Science Center, Hunan Normal University, Changsha 410013, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruoyu","family":"Han","sequence":"additional","affiliation":[{"name":"Key Laboratory of Model Animals and Stem Cell Biology in Hunan Province, Health Science Center, Hunan Normal University, Changsha 410013, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pingping","family":"He","sequence":"additional","affiliation":[{"name":"Key Laboratory of Model Animals and Stem Cell Biology in Hunan Province, Health Science Center, Hunan Normal University, Changsha 410013, China"},{"name":"Aging Health Research Center, School of Nursing, Health Science Center, Hunan Normal University, Changsha 410013, China"},{"name":"Engineering Research Center of Reproduction and Translational Medicine of Hunan Province, Hunan Normal University, Changsha 410013, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,8,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"16520","DOI":"10.1074\/jbc.M011205200","article-title":"5-Lipoxygenase interacts with coactosin-like protein","volume":"276","author":"Provost","year":"2001","journal-title":"J. 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