Canagliflozin, dapagliflozin, and empagliflozin consistently reduced progression of chronic kidney disease and risk of end-stage kidney disease in both diabetic and non-diabetic CKD patients independent of glycemic control as demonstrated in CREDENCE, DAPA-CKD, and EMPA-KIDNEY trials.
Do SGLT2 inhibitors improve renal outcomes in diabetic and non-diabetic individuals with chronic kidney disease?
SGLT2 inhibitors provide profound renoprotective effects in CKD patients regardless of diabetes status, driven by non-glycemic mechanisms, shifting the treatment paradigm toward organ protection.
A major healthcare burden and cause of high morbidity and mortality rates, chronic kidney disease (CKD) is a major concern in global health. We urgently need new and innovative therapeutic approaches because the progression of the disease has not been stopped, even though the main strategy for CKD management has been to maintain strict glycemic control and inhibit the renin-angiotensin-aldosterone system (RAAS). The impressive renoprotective activity of sodium-glucose cotransporter-2 (SGLT2) inhibitors extends far beyond their glucose-lowering effects.1,2 These drugs were first developed as antihyperglycemic medicines for type 2 diabetes mellitus. Evidence suggests that SGLT2 inhibitors may successfully halt the course of CKD in both diabetic and nondiabetic individuals, even when little changes in glycemic indices are detected. This conclusion is supported by recent preclinical investigations and large-scale cardiovascular and renal outcome trials.3,4 The renoprotective properties of SGLT2 inhibitors are attributed to their diverse non-glycemic actions, such as the normalization of tubuloglomerular feedback, reduction of intraglomerular pressure, suppression of renal inflammation and fibrosis, enhancement of renal oxygenation, reduction of oxidative stress, modulation of cellular energy metabolism, and reduction of serum uric acid levels.5-7 In addition, these drugs have shown beneficial actions on renal hemodynamics and tubular workload, thus protecting the integrity of nephrons and slowing the progression of end-stage kidney disease.8 In addition to glucose reduction, SGLT2 inhibitors have renoprotective effects, and this review seeks to summarize the current molecular and clinical information on these effects, as well as future research possibilities.
B. Venkata Lakshmi1*, L. Sahana2, K. Kujitha3, Dr. M. Tabitha Sharon4, Dr. K. Padmalatha5 (Tue,) conducted a review in Patients with chronic kidney disease including diabetic and non-diabetic individuals. SGLT2 inhibitors (canagliflozin, dapagliflozin, empagliflozin) vs. Placebo or standard of care including RAAS blockade was evaluated on Renal composite outcomes including progression to end-stage kidney disease (ESKD), doubling of serum creatinine, sustained decline in eGFR, renal or cardiovascular mortality, albuminuria progression. Canagliflozin, dapagliflozin, and empagliflozin consistently reduced progression of chronic kidney disease and risk of end-stage kidney disease in both diabetic and non-diabetic CKD patients independent of glycemic control as demonstrated in CREDENCE, DAPA-CKD, and EMPA-KIDNEY trials.