Dapagliflozin

Jia Y, et al. Toxicology and Applied Pharmacology, 2026, 507, 117696.

In a high-fat diet/streptozotocin (HFD/STZ)-induced type 2 diabetic mouse model, dapagliflozin was experimentally applied to evaluate its neuroprotective efficacy in diabetes-associated cognitive dysfunction (DACD). Mice received dapagliflozin treatment followed by behavioral assessment using Y-maze, Morris water maze, and novel object recognition tests to quantify cognitive performance. Hippocampal tissues were subjected to histopathology, oxidative stress assays (SOD, catalase, MDA), ELISA-based inflammatory cytokine quantification, and integrated transcriptomic-metabolomic profiling. Mechanistically, dapagliflozin downregulated IDO1 and KMO while upregulating KYAT1, reprogramming kynurenine metabolism toward neuroprotection. In vitro, high-glucose-stimulated BV-2 microglia were treated with dapagliflozin, and TLR/MyD88 signaling and KMO overexpression assays confirmed pathway specificity. These experiments establish dapagliflozin as a metabolic and immunomodulatory regulator in DACD.

Dostal C, et al. Biomedicine & Pharmacotherapy, 2025, 193, 118771.

The cardioprotective application of dapagliflozin was investigated in an isolated working heart model using adult C57BL/6J mice subjected to 100 min cold cardioplegic arrest (St. Thomas' #2 solution) followed by 30 min reperfusion. Dapagliflozin was administered either 30 min prior to ischemia via perfusion buffer or as an adjunct to cardioplegia. Continuous hemodynamic monitoring quantified left ventricular contractility, aortic flow, and diastolic function. Myocardial biopsies were analyzed for high-energy phosphates and metabolic gene expression by RT-qPCR. Complementary in vitro studies in HUVECs and cardiac myoblasts assessed cell viability and energy charge following SGLT2i pretreatment. Pre-ischemic administration significantly enhanced functional recovery and metabolic resilience. These findings experimentally position dapagliflozin as a preconditioning agent to improve myocardial performance after ischemia/reperfusion.

Wang X, et al. Biochemical Pharmacology, 2026, 248, 117833.

Dapagliflozin was experimentally evaluated for anti-fibrotic efficacy in a high-fat diet/streptozotocin-induced diabetic mouse model and hyperglycemia-exposed renal tubular epithelial cells. Treatment groups received graded dapagliflozin dosing, with metformin as a comparator. Renal fibrosis was assessed via histopathology and collagen deposition analysis, alongside molecular quantification of MMP2, TGF-β1, phosphorylated Smad2/3, collagen III, and α-SMA. Mechanistic interrogation focused on STAT3 signaling: phosphorylation status and nuclear translocation were examined using protein analysis, and STAT3 knockdown experiments validated pathway involvement. Dapagliflozin dose-dependently suppressed profibrotic markers and inhibited STAT3 activation in vivo and in vitro. This experimental framework demonstrates dapagliflozin as a targeted modulator of STAT3-dependent fibrogenesis in diabetic nephropathy.