Sodium-glucose cotransporter-2 (SGLT2) inhibitors have emerged as one of the most significant advances in nephrology in recent decades. The CREDENCE trial (Perkovic et al., New England Journal of Medicine, 2019) evaluated canagliflozin in 4,401 patients with type 2 diabetes and CKD and demonstrated a 30 percent relative risk reduction in the composite primary endpoint of doubling of serum creatinine, ESRD, or renal or cardiovascular death, leading to early trial termination for efficacy.
ISN (International Society of Nephrology) has incorporated SGLT2 inhibitor evidence into international clinical guidance, including the ISN-supported 2022 KDIGO Clinical Practice Guideline for Diabetes Management in CKD, which recommends SGLT2 inhibitors for patients with type 2 diabetes and CKD with eGFR ≥20 mL/min/1.73 m². The DAPA-CKD trial (Heerspink et al., New England Journal of Medicine, 2020) extended these findings to patients with CKD regardless of diabetic status, demonstrating significant reductions in CKD progression and cardiovascular mortality with dapagliflozin.
Mechanistically, the renoprotective effects of SGLT2 inhibitors extend well beyond glycemic control. Intraglomerular pressure reduction through tubuloglomerular feedback modulation has been documented in micropuncture studies, and anti-inflammatory effects mediated through NLRP3 inflammasome suppression have been characterized in preclinical models reviewed by Packer in the European Heart Journal (2020).
The EMPA-KIDNEY trial (EMPA-KIDNEY Collaborative Group, New England Journal of Medicine, 2023) enrolled 6,609 patients with CKD, including those with eGFR as low as 20 mL/min/1.73 m² and low albuminuria, and demonstrated that empagliflozin significantly reduced disease progression and cardiovascular death irrespective of albuminuria level or diabetic status, substantially expanding the eligible patient population for SGLT2 inhibitor therapy.
The International Society of Nephrology has emphasized the implementation challenges associated with these findings, noting that SGLT2 inhibitors remain unavailable or unaffordable for many patients in LMICs. ISN’s access and equity agenda, outlined in the ISN Global Kidney Health Roadmap (Levin et al., Kidney International, 2023), identifies generic formulations and procurement programs as critical priorities for equitable access to nephroprotective therapy.