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Medications that may offer clinical benefits to all three conditions are being developed. Glucagon\u2010like peptide\u20101 receptor agonists (GLP\u20101RAs) are approved for the management of T2D and obesity and there is great interest in evaluating higher doses of available GLP\u20101RAs and developing novel GLP\u20101RA\u2010based co\u2010agonists to provide greater reductions in glycated hemoglobin (HbA1c) and body weight as well as modifying NAFLD\/NASH complications in clinically meaningful ways. High\u2010dose GLP\u20101RAs and multi\u2010hormonal strategies including GLP\u20101R agonism have either already been approved or are in development for managing T2D, obesity, or NASH. We provide a mechanistic outline with a detailed summary of the available clinical data and ongoing trials that are adjudicating the impact of high\u2010dose GLP\u20101RAs, unimolecular, and multimolecular GLP\u20101R\u2010based co\u2010agonists in populations living with T2D, obesity, or NASH. The available trial findings are aligned with preclinical observations, showing clinical efficacy and safety thus providing optimism for the expansion of GLP\u20101R\u2010based drug classes for managing the triad of T2D, obesity and NASH. Development, access, and wide\u2010spread utilization of these new therapeutic approaches will offer important opportunities to markedly improve the collective global burden of T2D, obesity, and NASH.<\/jats:p>","DOI":"10.1111\/obr.13663","type":"journal-article","created":{"date-parts":[[2023,11,16]],"date-time":"2023-11-16T04:04:46Z","timestamp":1700107486000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":26,"title":["Management of type 2 diabetes, obesity, or nonalcoholic steatohepatitis with high\u2010dose GLP\u20101 receptor agonists and GLP\u20101 receptor\u2010based co\u2010agonists"],"prefix":"10.1111","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1788-3255","authenticated-orcid":false,"given":"Ronald M.","family":"Goldenberg","sequence":"first","affiliation":[{"name":"LMC Diabetes &amp; Endocrinology  Concord Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7456-9396","authenticated-orcid":false,"given":"Jeremy D.","family":"Gilbert","sequence":"additional","affiliation":[{"name":"Division of Endocrinology and Metabolism, Sunnybrook Health Sciences Centre, and Department of Medicine University of Toronto  Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-8221-4916","authenticated-orcid":false,"given":"Priya","family":"Manjoo","sequence":"additional","affiliation":[{"name":"Department of Endocrinology University of British Columbia, and Cardiometabolic Collaborative Clinic, Vancouver Island Health Authority  Vancouver British Columbia Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4355-1764","authenticated-orcid":false,"given":"Sue D.","family":"Pedersen","sequence":"additional","affiliation":[{"name":"C\u2010ENDO Diabetes &amp; Endocrinology Clinic Calgary  Calgary Alberta Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1745-6381","authenticated-orcid":false,"given":"Vincent C.","family":"Woo","sequence":"additional","affiliation":[{"name":"Section of Endocrinology, Health Sciences Centre, Max Rady College of Medicine University of Manitoba  Winnipeg Manitoba Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9171-8952","authenticated-orcid":false,"given":"Julie A.","family":"Lovshin","sequence":"additional","affiliation":[{"name":"Division of Endocrinology and Metabolism, Sunnybrook Health Sciences Centre, and Department of Medicine University of Toronto  Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,11,15]]},"reference":[{"key":"e_1_2_15_2_1","unstructured":"World Health Organization.Obesity and overweight.2021. 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