sodium glucose cotransporter-2 (SGLT2) inhibitors

Overview

Sodium-glucose cotransporter-2 (SGLT2) inhibitors are a class of glucose-lowering therapies used primarily in type 2 diabetes mellitus. They act by blocking SGLT2 in the proximal renal tubule, reducing renal glucose reabsorption and promoting urinary glucose excretion. Beyond their glycemic effects, this drug class has become clinically important because of consistent cardiovascular and renal benefits observed across multiple patient populations, particularly in type 2 diabetes, heart failure, and chronic kidney disease.

In contemporary practice, SGLT2 inhibitors are often discussed alongside other cardiometabolic therapies such as glucagon-like peptide-1 agonists, finerenone, metformin, and statins. Recent research has focused on their effects on heart failure risk, Blood Pressure, kidney outcomes, and broader cardiovascular protection, including in patients with arterial hypertension, coronary artery disease, and chronic renal insufficiency. Individual agents in the class include empagliflozin and dapagliflozin, which are frequently used as representative SGLT2 inhibitors in clinical and translational studies.

Focus of Latest Publications

Recent investigations have focused on the cardiovascular and renal protective effects of SGLT2 inhibitors across diverse patient populations and clinical scenarios. Studies have demonstrated benefits in heart failure with both preserved and reduced ejection fraction, including improved diastolic function after transcatheter aortic valve implantation and reduced mortality when initiated early following acute myocardial infarction. In patients with diabetes and end-stage kidney disease, SGLT2i exposure was associated with lower all-cause mortality, reduced sepsis risk, and fewer hospitalizations compared to dipeptidyl peptidase-4 inhibitors. These agents have also shown renoprotective effects in diabetic kidney disease and preserved kidney function, with evidence suggesting that acute changes in estimated glomerular filtration rate may inform long-term clinical benefit in chronic kidney disease populations.

Metabolic effects and glycemic control remain central to SGLT2i efficacy in real-world practice. Monotherapy with SGLT2 inhibitors achieved the highest rates of glycemic control in Hispanic populations, with rates exceeding 85% achieving target hemoglobin A1c levels. Blood pressure reduction represents a key mechanism, though the magnitude of reduction varies with patient-specific factors including baseline characteristics and comorbidities. However, these agents are associated with increased genitourinary infection risk—including urinary tract infections and genital tract infections—particularly when combined with dipeptidyl peptidase-4 inhibitors, though this adverse effect profile appears population-dependent.

Combination therapy strategies have emerged as areas of active investigation. Combined use of SGLT2 inhibitors with glucagon-like peptide-1 receptor agonists has shown potential for synergistic benefits in metabolic dysfunction-associated steatotic liver disease, with evidence suggesting superior liver fibrosis outcomes and cardiovascular protection compared to monotherapy. Similarly, co-administration with finerenone demonstrated enhanced renal protection in immunoglobulin A nephropathy compared to monotherapy, while combination with statins showed promising effects on ejection fraction in ischemic heart disease patients.

Emerging applications have broadened beyond traditional cardiovascular and metabolic indications. SGLT2 inhibitors have been investigated for their potential roles in reducing seizure risk, slowing progression of early-stage pulmonary malignancies, improving survival in bladder cancer patients, and providing neuroprotective benefits in mild cognitive impairment. In patients with Type 1 diabetes and chronic kidney disease, these agents were observed to be used in clinical practice and associated with favorable outcome patterns, though evidence remains limited. Additionally, despite concerns about weight and muscle loss, SGLT2 inhibitors were associated with lower incidence of frailty-related events compared to dipeptidyl peptidase-4 inhibitor therapy in heart failure patients, suggesting potential benefits that warrant further investigation in vulnerable populations.

Key Publications

• NEWJun Nephrotoxic medication burden and drug-related problems in patients with chronic kidney disease using SGLT2 inhibitors. (Renal failure, 2026, PMID 42336367): "Sodium-glucose cotransporter 2 inhibitors (SGLT2i) are increasingly prescribed because of their renal and cardiovascular benefits."
• NEWJun Semaglutide and Risk of Adult-Onset Seizure: A Target Trial Emulation. (Neurology, 2026, PMID 42308439): "We evaluated whether semaglutide initiation is associated with a lower incidence of adult-onset seizure compared with sodium-glucose cotransporter 2 inhibitors (SGLT2i) and other glucose-lowering drugs (GLDs) in adults with type 2 diabetes."
• Jun Survival association of GLP-1 receptor agonists and SGLT2 inhibitors in bladder cancer patients. (Urologic oncology, 2026, PMID 42224918): "To evaluate whether exposure to glucagon-like peptide-1 receptor agonists (GLP-1) or sodium-glucose cotransporter 2 inhibitors (SGLT2) is associated with overall survival (OS) in adults with treated bladder cancer."
• Jul Short-term comparative effects of semaglutide, either alone or in conjunction with canagliflozin, on early diabetic kidney disease. (Pakistan journal of pharmaceutical sciences, 2026, PMID 42170981): "To date, SGLT2 inhibitors and GLP-1 receptor agonists are known to provide renoprotective and metabolic benefits; however, there is limited evidence available regarding the combined use of these treatments in early DKD."
• May Real-world evidence of urinary tract infections and genital tract infections with sodium-glucose cotransporter-2 inhibitors (SGLT2i) alone or in combination with dipeptidyl peptidase-4 inhibitors (DPP4i) in individuals with type-2 diabetes mellitus in India. (BMC endocrine disorders, 2026, PMID 42163184): "Sodium-glucose cotransporter-2 inhibitors (SGLT2i), increasingly used in India, are linked to higher genitourinary infection (UTI/GTI) rates in people with T2D worldwide, yet real-world evidence in India remains limited."
• Jun Precision Prescribing of SGLT2 Inhibitors in Individuals With Type 2 Diabetes for Primary Prevention of Heart Failure: Model Development and Validation Study. (Diabetes care, 2026, PMID 42160591): "Sodium-glucose cotransporter 2 inhibitors (SGLT2i) reduce heart failure (HF) risk in type 2 diabetes (T2D) and are recommended for patients with T2D who have atherosclerotic cardiovascular disease (ASCVD), HF, or chronic kidney disease (CKD)."
• Jun Factors That Influence Blood Pressure Changes With the Use of Sodium-Glucose Cotransporter 2 Inhibitors in People With Type 2 Diabetes. (Pharmacotherapy, 2026, PMID 42130462): "Multiple clinical trials have reported variable reductions in blood pressure with sodium-glucose cotransporter 2 (SGLT2) inhibitors."
• May The Effect of the combination therapy of statin and dapagliflozin, a selective inhibitor of sodium_glucose Co-transporter type 2, in the treatment of Ischemic heart disease with heart failure: A randomized controlled trial. (European journal of clinical pharmacology, 2026, PMID 42133048): "Although both are well known for diminishing cardiovascular risk and heart failure-related mortality, the possible synergistic benefits of using them together have not been thoroughly investigated."
• May Multi-Omics and network-based exploration of potential molecular pathways in heart failure relevant to left bundle branch pacing response heterogeneity: Immune remodeling, hub gene identification, and drug repurposing hypotheses. (PloS one, 2026, PMID 42113804): "Drug prediction suggested multiple candidates, including β-blockers, RAAS inhibitors, anti-fibrotic agents, vericiguat, metformin, and SGLT2 inhibitors."
• May Effectiveness and Safety of SGLT2 Inhibitor Initiation in Sacubitril-Valsartan Users with Heart Failure: A Population-Based Cohort Study. (European heart journal. Cardiovascular pharmacotherapy, 2026, PMID 42098937): "Large-scale real-world evidence regarding outcomes of sodium-glucose cotransporter-2 inhibitors (SGLT2i) initiation added to sacubitril-valsartan is currently limited."