{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,6,3]],"date-time":"2025-06-03T04:09:57Z","timestamp":1748923797789,"version":"3.41.0"},"reference-count":53,"publisher":"Georg Thieme Verlag KG","issue":"05","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Drug Res (Stuttg)"],"published-print":{"date-parts":[[2025,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Sotagliflozin, a dual SGLT1\/2 inhibitor, enhances glucagon like peptide-1\n                        (GLP-1) levels and GLP-1 receptor agonists are used to manage non-alcoholic\n                        fatty liver disease (NAFLD). Study investigates the effects of sotagliflozin\n                        on NAFLD, alone and combined with linagliptin, comparing outcomes in\n                        normoglycemic and hyperglycemic animal models.<\/jats:p><jats:p>Obese fatty liver disease (FLD) model was induced by high-fat diet (HFD)\n                        feeding, while a diabetic non-alcoholic steatohepatitis (NASH) model was\n                        developed by administering a single dose of streptozotocin to neonatal mice,\n                        followed by HFD feeding post-weaning. At termination of the study,\n                        parameters including biochemical markers, inflammatory cytokines, hepatic\n                        lipid content, and histopathology were assessed.<\/jats:p><jats:p>In NASH mice, sotagliflozin and linagliptin reduced hepatic triglycerides by\n                        60% and 44%, respectively, and cholesterol by 46% and 49%. Their combination\n                        further decreased triglycerides by 68.5% and cholesterol by 83.9%. In FLD\n                        mice, sotagliflozin and linagliptin reduced triglycerides by 33% and 17%,\n                        respectively, and cholesterol by 46% and 21%. Combination treatment offered\n                        no benefit, reducing triglycerides by 38% and cholesterol by 27%. Both the\n                        treatments improved plasma fibroblast growth factor 21, hepatic\n                        interlukin-6, glucose tolerance, steatosis and mitigated fat pad weight, but\n                        their combination did not show additional benefit. However, combination\n                        treatment demonstrated added benefit in modulating NAFLD activity score,\n                        liver enzymes, glycogenated hepatic nuclei, plasma glucose and active GLP-1\n                        levels.<\/jats:p><jats:p>Study underscores sotagliflozin\u02bcs potential to mitigate NAFLD and highlights\n                        the benefit of combining it with linagliptin in hyperglycemic NASH model,\n                        which showed limited efficacy in normoglycemic FLD mice.<\/jats:p>","DOI":"10.1055\/a-2557-8927","type":"journal-article","created":{"date-parts":[[2025,4,14]],"date-time":"2025-04-14T23:09:51Z","timestamp":1744672191000},"page":"129-139","source":"Crossref","is-referenced-by-count":0,"title":["Therapeutic Potential of Sotagliflozin in Animal Models of\n                    Non-alcoholic Fatty Liver Disease with and without Diabetes"],"prefix":"10.1055","volume":"75","author":[{"given":"Nitin J.","family":"Deshmukh","sequence":"additional","affiliation":[{"name":"D.S.T.S. Mandal\u2019s Collage of Pharmacy, Solapur, Maharashtra,\n                    India"},{"name":"Wockhardt Research Centre, D4 MIDC, Chikalthana, Aurangabad,\n                    Maharashtra, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M. S.","family":"Kalshetti","sequence":"additional","affiliation":[{"name":"D.S.T.S. Mandal\u2019s Collage of Pharmacy, Solapur, Maharashtra,\n                    India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mohan","family":"Patil","sequence":"additional","affiliation":[{"name":"Wockhardt Research Centre, D4 MIDC, Chikalthana, Aurangabad,\n                    Maharashtra, India"},{"name":"Curtin Medical School, Curtin Health Innovation Research Institute,\n                    Curtin University, Perth, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Manohar","family":"Nandanwar","sequence":"additional","affiliation":[{"name":"Wockhardt Research Centre, D4 MIDC, Chikalthana, Aurangabad,\n                    Maharashtra, India"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ganesh V.","family":"Sangle","sequence":"additional","affiliation":[{"name":"Wockhardt Research Centre, D4 MIDC, Chikalthana, Aurangabad,\n                    Maharashtra, India"},{"name":"Kashiv BioSciences Private Limited, Ahmedabad, Gujarat"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"194","published-online":{"date-parts":[[2025,4,14]]},"reference":[{"key":"ref1","doi-asserted-by":"crossref","first-page":"356","DOI":"10.1159\/000444547","article-title":"Non-Alcoholic steatohepatitis: from pathophysiology to novel therapies","volume":"34","author":"D Jahn","year":"2016","journal-title":"Dig Dis"},{"key":"ref2","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1111\/liv.13299","article-title":"The epidemiology of non-alcoholic fatty liver disease","volume":"37","author":"S Bellentani","year":"2017","journal-title":"Liver International"},{"key":"ref3","doi-asserted-by":"crossref","first-page":"431","DOI":"10.1590\/s0004-2803.201900000-67","article-title":"Impact of current diet at the risk of non-alcoholic fatty liver disease\n                    (NAFLD)","volume":"56","author":"SM B Duarte","year":"2019","journal-title":"Arq 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      diabetic mice","volume":"3","author":"P Millar","year":"2017","journal-title":"J Endocrinol"},{"key":"ref54","doi-asserted-by":"crossref","first-page":"489","DOI":"10.1111\/dom.12838","article-title":"Effects on \u03b1- and \u03b2-cell function of sequentially adding empagliflozin and\n                    linagliptin to therapy in people with type 2 diabetes previously receiving\n                    metformin: an exploratory mechanistic study","volume":"19","author":"T Forst","year":"2017","journal-title":"Diabetes Obes Metab"},{"key":"ref55","doi-asserted-by":"crossref","first-page":"1447","DOI":"10.1016\/j.celrep.2019.07.009","article-title":"The GLP1R agonist liraglutide reduces hyperglucagonemia induced by the SGLT2\n                    inhibitor dapagliflozin via somatostatin release","volume":"28","author":"C Saponaro","year":"2019","journal-title":"Cell Rep"}],"container-title":["Drug 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