SGLT2 Inhibitors for Diabetic Kidney Disease Prevention: Mechanisms, Clinical Evidence, and Guidelines

Nambi Namusisi H.

School of Natural and Applied Sciences Kampala International University Uganda

                                                                                                        ABSTRACT
Diabetic kidney disease remained a leading cause of end stage renal disease globally, affecting approximately 40% of individuals with diabetes mellitus. Sodium glucose cotransporter 2 inhibitors represented a novel therapeutic class originally developed for glycemic control but have demonstrated profound renoprotective effects independent of glucose-lowering mechanisms. This review examined the biochemical mechanisms underlying the renoprotective effects of sodium glucose cotransporter 2 inhibitors, evaluated the clinical evidence supporting their use in diabetic kidney disease prevention, and synthesized current guideline recommendations for their implementation in clinical practice. A comprehensive synthesis of mechanistic studies, randomized controlled trials, meta-analyses, and international clinical practice guidelines published through early 2025 was conducted to evaluate sodium glucose cotransporter 2 inhibitor efficacy and safety in diabetic kidney disease. Sodium glucose cotransporter 2 inhibitors exerted renoprotection through multiple interconnected mechanisms, including restoration of tubuloglomerular feedback, reduction of intraglomerular pressure, attenuation of oxidative stress and inflammation, and modulation of renal energy metabolism. Recent evidence extended these benefits to patients with chronic kidney disease irrespective of diabetes status. Current guidelines recommend sodium glucose cotransporter 2 inhibitors as foundational therapy alongside renin angiotensin system blockade for patients with diabetic kidney disease and preserved ejection fraction. Sodium glucose cotransporter 2 inhibitors represented a paradigm shift in diabetic kidney disease management, offering robust renoprotection through pleiotropic mechanisms with an acceptable safety profile, though implementation barriers and knowledge gaps regarding optimal patient selection persist.

Keywords: Sodium glucose cotransporter 2 inhibitors, Diabetic kidney disease, Renoprotection, tubuloglomerular
feedback, chronic kidney disease.

CITE AS: Nambi Namusisi H. (2026). SGLT2 Inhibitors for Diabetic Kidney Disease Prevention: Mechanisms, Clinical Evidence, and Guidelines. Research Output Journal of Engineering and Scientific Research 5(1): 29-35. https://doi.org/10.59298/ROJESR/2026/5.12935