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The current preclinical research sought to investigate the effect of sotagliflozin on the secretion of fat\u2010regulating peptides such as GLP\u20101, glucagon and fibroblast growth factor 21 (FGF21) and their prospective association with sotagliflozin's potential beneficial effects on dyslipidaemia. During an oral fat tolerance test in mice, sotagliflozin substantially increased GLP\u20101 and insulin concentrations. Although sotagliflozin alone did not ameliorate postprandial lipemia, its combination with linagliptin (DPP\u2010IV inhibitor) significantly improved lipid tolerance comparable to orlistat (lipase inhibitor). In a triton\u2010induced hypertriglyceridemia model, sotagliflozin, along with other medications (fenofibrate, exenatide and linagliptin) reduced fat excursion; however, co\u2010administration with linagliptin provided no extra advantage. Furthermore, sotagliflozin stimulated glucagon secretion in the alpha TC1.6 cells and healthy mice, which resulted in an increased circulating FGF21 and \u03b2\u2010hydroxybutyrate concentration. Finally, chronic treatment of sotagliflozin in high\u2010fat diet (HFD)\u2010fed obese mice resulted in reduced body weight gain, liver triglyceride, cholesterol, interleukin\u20106 (IL\u20106) and tumour necrosis factor alpha (TNF\u2010\u03b1) levels compared with the placebo group. However, the addition of linagliptin did not provide any additional benefit. In conclusion, sotagliflozin was found to have an effect on GLP\u20101 and also stimulate the release of glucagon and FGF21, which are important for regulating fat metabolism. Therefore, sotagliflozin might represent a potential therapeutic approach for the treatment of diabetic dyslipidemia and steatohepatitis.<\/jats:p>","DOI":"10.1111\/1440-1681.13854","type":"journal-article","created":{"date-parts":[[2024,3,26]],"date-time":"2024-03-26T01:49:49Z","timestamp":1711417789000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Exploring the modulatory effects of sotagliflozin on dyslipidemia in mice: The role of glucagon, fibroblast growth factor 21 and glucagon\u2010like peptide 1"],"prefix":"10.1111","volume":"51","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-6555-2486","authenticated-orcid":false,"given":"Nitin J.","family":"Deshmukh","sequence":"first","affiliation":[{"name":"D.S.T.S. Mandal's Collage of Pharmacy  Solapur India"},{"name":"Wockhardt Research Centre  Aurangabad India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M. 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