SGLT2 inhibitor dapagliflozin
SGLT2 inhibitor dapagliflozin
Overview
Dapagliflozin is a sodium-glucose cotransporter 2 (SGLT2) inhibitor used as a therapeutic agent, most prominently in type 2 diabetes. By inhibiting SGLT2-mediated glucose reabsorption in the kidney, it promotes urinary glucose excretion and lowers blood glucose. Beyond glycemic control, dapagliflozin has been investigated for broader cardiometabolic and organ-protective effects, including potential benefits in the kidney, heart, and other tissues.
In recent biomedical research, dapagliflozin has been studied not only as a glucose-lowering therapy but also as a modulator of disease-associated pathways such as oxidative stress, ferroptosis, TGF-β signaling, and inflammatory injury. These studies place dapagliflozin within the broader class of sodium glucose cotransporter-2 (SGLT2) inhibitors, alongside agents such as empagliflozin, and suggest that its effects may extend into renal protection, cardiovascular remodeling, metabolic regulation, and possibly neurobiological outcomes.
Focus of Latest Publications
Recent publications on dapagliflozin have focused on its comparative effectiveness in cardiometabolic disease, with several real-world and modeling studies examining outcomes in type 2 diabetes, heart failure, chronic kidney disease, and cardiovascular-kidney-metabolic syndrome. A prospective cohort study in heart failure with reduced ejection fraction noted that dapagliflozin and empagliflozin are both sodium-glucose cotransporter-2 inhibitors with equivalent Class IA guideline recommendations. In a nationwide propensity-matched study of adults with type 2 diabetes, dapagliflozin was compared with empagliflozin and dipeptidyl peptidase-4 inhibitors; the authors reported broadly similar outcomes between dapagliflozin and empagliflozin consistent with a class effect, while empagliflozin showed lower risks of all-cause hospitalization and kidney events versus dipeptidyl peptidase-4 inhibitors. A separate cost-offset analysis in adults with cardiovascular-kidney-metabolic syndrome in Spain modeled the clinical events and healthcare costs associated with dapagliflozin over 3 years from the Spanish National Health System perspective.
Other recent studies have explored dapagliflozin in kidney disease and transplant settings. In diabetic nephropathy, dapagliflozin was reported to ameliorate renal histopathological changes and to modulate ferroptosis-related markers in mice and high-glucose-cultured human renal tubular epithelial cells, with effects linked to activation of the Nrf2/HO-1 signaling pathway. In inactive lupus nephritis with residual proteinuria, a randomized crossover trial evaluated the efficacy and safety of dapagliflozin. In de novo kidney transplant recipients, the DEAK study was designed as a randomized, double-blind, placebo-controlled trial to assess dapagliflozin’s effects on kidney structure, function, histopathology, metabolic outcomes, and safety, reflecting interest in extending SGLT2 inhibition to transplant populations that were excluded from earlier studies.
Preclinical work has also examined dapagliflozin in cardiovascular, neurologic, and metabolic contexts. In a mouse model of HIV-associated cardiac disease, dapagliflozin attenuated cardiac fibrosis and steatosis and preserved diastolic function, with the authors attributing these effects to inhibition of TGFβ signaling. In a rat model of diabetic cardiomyopathy, dapagliflozin reduced oxidative stress markers, improved histopathology, and increased connexin-43 expression, suggesting potential protection against gap junction disruption. Additional experimental studies reported dapagliflozin pretreatment attenuating focal cerebral ischemia-reperfusion injury in rats and dapagliflozin improving cognitive dysfunction-related biochemical and behavioral measures in streptozotocin/nicotinamide-induced diabetic rats, alongside in silico interactions with targets including acetylcholinesterase, SGLT1/2, RAGE, and interleukin-1β.
Several publications also addressed broader metabolic and pharmacologic effects of dapagliflozin. In hospitalized patients with type 2 diabetes receiving continuous subcutaneous insulin infusion, a retrospective matched study compared add-on henagliflozin or dapagliflozin with CSII alone. Another mouse study examined time-of-day differences in plasma N-glycome changes after dapagliflozin dosing in the morning or at night, finding that nighttime administration normalized several high-fat-diet-induced glycan alterations despite limited effects on blood glucose or body weight. Together, these studies highlight ongoing interest in dapagliflozin not only as a glucose-lowering therapy, but also as a candidate for organ-protective and disease-modifying effects across cardiovascular, renal, neurologic, and inflammatory conditions.