SGLT2 Inhibitors in Diabetic Nephropathy: A Systematic Review of SGLT2 Inhibitors Benefits in Diabetic Nephropathy

Background: Diabetic nephropathy (DN), which affects 25–40% of those with type 2 diabetes (T2DM), is the main cause of end-stage kidney disease (ESKD) and a significant microvascular effect of diabetes mellitus. The need for better treatments is highlighted by the fact that disease progression frequently continues even after improvements in glycemic management and renin-angiotensin system (RAS) inhibition. Since they provide advantages beyond glucose management, such as kidney protection, sodium-glucose cotransporter-2 (SGLT2) inhibitors have become an attractive therapy option. Objective: This systematic review aims to evaluate the therapeutic potential, safety, and efficacy of SGLT2 inhibitors in the treatment of DN, with a focus on the renoprotective effects they have on individuals with type 2 diabetes. Method: A thorough literature search was carried out up until April 10, 2025, using PubMed, Google Scholar, PubMed Central, and ScienceDirect in accordance with PRISMA 2020 standards. Cohort studies published in English within the previous five years, meta-analyses, and randomized controlled trials (RCTs) were all considered eligible studies. The Quality Assessment Tool for Observational Cohort Studies, the Cochrane Risk of Bias Tool for RCTs, and AMSTAR 2 for meta-analyses were used to evaluate the risk of bias. Result: The inclusion of 243,682 patients from eight high-quality studies (two meta-analyses, three RCTs, and three cohort studies) was noted. SGLT2 inhibitors showed considerable renoprotective benefits, such as a 20–40% decrease in UACR, a 0.7–1.81 mL/min/year reduction in the rate of eGFR decline, and a 34–36% relative risk reduction in composite renal outcomes. Empagliflozin and dapagliflozin were especially effective due to their mechanisms, which included enhanced renal oxygenation, decreased glomerular hyperfiltration, and anti-inflammatory effects. The safety profiles were encouraging, with manageable adverse effects like genital infections and uncommon occurrences of diabetic ketoacidosis (DKA). Conclusion: Given their strong renal protective effects in diabetic nephropathy, SGLT2 inhibitors should be started early in Type 2 diabetes patients, with or without chronic kidney disease. They are a cornerstone in the management of DN since their advantages span all phases of renal illness. Additional study is needed to examine long-term results and comparative effectiveness among various SGLT2 medications.