SGLT2 inhibitors in chronic kidney disease: cardiorenal outcomes, safety, and implementation in primary care

Background: Chronic kidney disease (CKD) is linked to high cardiovascular morbidity and mortality. Many patients remain at risk despite standard treatment. This review assessed the renal, cardiovascular, safety, and primary care implementation outcomes of sodium-glucose cotransporter-2 (SGLT2) inhibitors in CKD, including patients with and without diabetes. Methods: This systematic review followed PRISMA 2020 guidelines. PubMed, Scopus, and Google Scholar were searched for English-language human studies published between 2016 and 2026. Reference lists of eligible articles were also manually screened. Eligible studies included randomized controlled trials and primary observational studies evaluating SGLT2 inhibitors in patients with CKD, with or without diabetes. Studies reporting renal, cardiovascular, safety, or primary care implementation outcomes were included. Data were extracted using a standardized form and synthesized qualitatively because of clinical and methodological heterogeneity. Results: Fifteen primary studies were included, comprising randomized controlled trials and observational studies. Across landmark clinical trials and real-world studies, SGLT2 inhibitors slowed eGFR decline, reduced albuminuria, and lowered the risk of kidney and heart failure hospitalization. Renal and cardiovascular benefits were observed in patients with and without diabetes. SGLT2 inhibitors were generally well tolerated, with genital mycotic infections and volume depletion being the most reported adverse events, while serious adverse events were uncommon. Real-world studies consistently identified underprescription and implementation barriers in primary care. Discussion: SGLT2 inhibitors are foundational therapies for CKD, providing consistent renal and cardiovascular benefits with an acceptable safety profile in patients with and without diabetes. However, substantial gaps remain in their implementation in primary care. Improving early identification of eligible patients, clinician awareness, and integration of guideline-directed prescribing into routine practice may help reduce CKD progression and cardiovascular events.