Sotagliflozin is the first dual SGLT1/2 inhibitor antidiabetic drug approved by the US Food and Drug Administration for the management of heart failure. SGLT1/2 inhibition is observed to potentiate the secretion of the incretin hormone, glucagon-like peptide-1 (GLP-1). The current preclinical research sought to investigate the effect of sotagliflozin on the secretion of fat-regulating peptides such as GLP-1, 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-1 and insulin concentrations. Although sotagliflozin alone did not ameliorate postprandial lipemia, its combination with linagliptin (DPP-IV inhibitor) significantly improved lipid tolerance comparable to orlistat (lipase inhibitor). In a triton-induced hypertriglyceridemia model, sotagliflozin, along with other medications (fenofibrate, exenatide and linagliptin) reduced fat excursion; however, co-administration 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 β-hydroxybutyrate concentration. Finally, chronic treatment of sotagliflozin in high-fat diet (HFD)-fed obese mice resulted in reduced body weight gain, liver triglyceride, cholesterol, interleukin-6 (IL-6) and tumour necrosis factor alpha (TNF-α) 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-1 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.
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http://dx.doi.org/10.1111/1440-1681.13854 | DOI Listing |
JACC Adv
December 2024
Division of Cardiac Surgery, St. Michael's Hospital of Unity Health Toronto, Toronto, Ontario, Canada.
Background: Valvular heart disease (VHD) management has evolved rapidly in recent decades, but disparities in health care access persist among countries with varying socioeconomic backgrounds.
Objectives: The purpose of this study was to investigate global mortality trends from VHD and assess the difference between middle- and high-income countries.
Methods: We obtained mortality data from the World Health Organization Mortality Database for VHD and its subgroups (rheumatic valvular disease [RVD], infective endocarditis [IE], aortic stenosis [AS], and mitral regurgitation [MR]) from 2000 to 2019.
JACC Adv
January 2025
Heart Failure Clinics, Instituto do Coracao, Hospital das Clínicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, Sao Paulo, Brazil.
Background: Worsening heart failure (WHF) challenges health care with frequent rehospitalizations and reduced quality of life for patients. Despite therapeutic advances, high rehospitalization risks highlight the urgent need for new treatments.
Objectives: This study evaluated the effectiveness of initiating novel therapies during hospitalization or vulnerable phase for WHF patients to reduce rehospitalization risks and determine the optimal treatment sequence.
Molecules
December 2024
Department of Medicinal Chemistry, Medical University of Lublin, Jaczewskiego 4, 20-090 Lublin, Poland.
This study represents the first-time experimental analysis of lipophilicity for antidiabetic drugs from the gliflozin class using chromatographic methods alongside computational approaches. The lipophilicity of five gliflozins (canagliflozin (CANA), dapagliflozin (DAPA), empagliflozin (EMPA), ertugliflozin (ERTU), and sotagliflozin (SOTA)) was assessed using R and log k parameters with RP8, RP18, and CN coatings, while methanol and acetonitrile were used as organic modifiers. To enhance the reliability, six reference substances with established lipophilicity values (0.
View Article and Find Full Text PDFJ Am Coll Cardiol
January 2025
Mount Sinai Fuster Heart Hospital, Icahn School of Medicine at Mount Sinai, New York, New York, USA. Electronic address: https://twitter.com/DLBHATTMD.
Background: In patients with ST-segment elevation myocardial infarction (STEMI) and multivessel coronary artery disease, most but not all randomized trials have reported that complete revascularization (CR) offers advantages over culprit vessel-only revascularization. In addition, the optimal timing and assessment methods for CR remain undetermined.
Objectives: The purpose of this study was to identify the optimal revascularization strategy in patients with STEMI and multivessel disease, using a network meta-analysis of randomized controlled trials.
Int J Cardiol
February 2025
Brigham and Women's Hospital Heart and Vascular Center, Boston, MA, USA; Baim Institute for Clinical Research, Boston, MA, USA. Electronic address:
Background: Patients with a history of coronary revascularization are at a higher risk for subsequent cardiovascular events and all-cause mortality. Lowering LDL-cholesterol (LDL-C) levels post-revascularization significantly reduces these risks.
Methods: This analysis compared LDL-C-lowering therapies at baseline and over time among patients with and without prior coronary revascularization in the GOULD registry (a prospective multicenter cohort study).
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