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.

Key Publications

• NEWJun Comparative effectiveness of dapagliflozin vs. empagliflozin on major adverse cardiovascular events in patients with heart failure with reduced ejection fraction: A real-world prospective cohort study. (British journal of clinical pharmacology, 2026, PMID 42357835): "Dapagliflozin and empagliflozin are sodium-glucose cotransporter-2 inhibitors (SGLT2i) with equivalent Class IA guideline recommendations in heart failure with reduced ejection fraction (HFrEF)."
• NEWJun Clinical events and healthcare costs of dapagliflozin in adults with cardiovascular-kidney-metabolic syndrome in Spain: a cost-offset analysis. (Journal of medical economics, 2026, PMID 42343656): "Dapagliflozin has demonstrated significant benefits in adults with type 2 diabetes (T2D), heart failure (HF) and CKD."
• NEWJun Head-to-head comparative effectiveness of empagliflozin versus dapagliflozin and DPP-4 inhibitors on clinical and metabolic outcomes: a nationwide propensity-matched study. (Scientific reports, 2026, PMID 42342812): "This retrospective study compared the clinical and metabolic effectiveness of empagliflozin (EMPA) versus dapagliflozin (DAPA) and dipeptidyl peptidase-4 inhibitors (DPP-4i) using real-world data from the Korean National Health Insurance Service (2013-2024)."
• NEWJun Dapagliflozin pretreatment attenuates focal cerebral ischemia-reperfusion injury in rats. (Molecular biology reports, 2026, PMID 42334656): "This study evaluated the prophylactic neuroprotective effects of dapagliflozin (Dapa), a sodium-glucose cotransporter 2 (SGLT2) inhibitor, in a non-diabetic rat model of cerebral ischemia/reperfusion (C/IR) injury."
• NEWJun Can sodium-glucose cotransporter 2 (SGLT2) inhibition preserve renal structure and function in de novo kidney transplant recipients? Protocol for a randomised, double-blind, placebo-controlled trial assessing the efficacy of dapagliflozin on kidney structure, function and safety in kidney transplant recipients in Norway-the DEAK study. (BMJ open, 2026, PMID 42315275): "The Dapagliflozin Early After Kidney Transplantation (DEAK) study aims to prospectively evaluate the effects of the SGLT2 inhibitor dapagliflozin on kidney function, histopathology and metabolic outcomes among de novo KTRs."
• May Role of suberoylanilide hydroxamic acid and dapagliflozin on Cx43 gene expression in diabetic cardiomyopathy rat's model. (Scientific reports, 2026, PMID 42156803): "SAHA demonstrated comparatively greater effects than dapagliflozin in preserving gap junction integrity and attenuating diabetic cardiomyopathy development, potentially through both antioxidant and epigenetics mechanisms, while Dapa enhances glycemic control although these findings are limited to a single-dose experimental model."
• May Dapagliflozin attenuates ferroptosis in diabetic nephropathy through activation of the Nrf2/HO‑1 signaling pathway. (International journal of molecular medicine, 2026, PMID 42099241): "Dapagliflozin (DAPA), a sodium‑glucose cotransporter 2 inhibitor, has demonstrated efficacy in attenuating DN progression and preserving renal function."
• May SGLT2 inhibitor dapagliflozin attenuates HIV-associated cardiac fibrosis, steatosis and diastolic dysfunction in a mouse model via inhibition of TGFβ signaling. (AIDS (London, England), 2026, PMID 42054528): "The sodium-glucose cotransporter type 2 inhibitor (SGLT2i) dapagliflozin has efficacy for cardiovascular disease (CVD) prevention in type 2 diabetes and is a promising therapy for the inflammatory component of CVD risk in PWH."
• May Time-of-Day Differences in the Plasma N-Glycome of Normal and Obese Mice and the Effects of Dapagliflozin Administered in the Morning or at Night. (Journal of proteome research, 2026, PMID 41948954): "with or without treatment using the sodium-glucose cotransporter 2 (SGLT2) inhibitor dapagliflozin (Dap), administered either in the morning or at night."
• May Efficacy and hypoglycemia-related safety of henagliflozin or dapagliflozin as add-on to CSII in hospitalized patients with T2DM: A retrospective matched study using continuous glucose monitoring. (Journal of diabetes and its complications, 2026, PMID 41916043): "To compare the efficacy and hypoglycemia-related safety of add-on henagliflozin or dapagliflozin to continuous subcutaneous insulin infusion (CSII) versus CSII alone in hospitalized patients with type 2 diabetes mellitus (T2DM)."