Studies of either intensive glucose-lowering therapy or specific glucose-lowering drugs versus standard of care have consistently shown that correction of hyperglycemia reduces microvascular complications, including nephropathy, in people with T2D. Therefore, progressive renal impairment increases the risk of patients experiencing not only renal but also CV morbidity and mortality. Indeed, up to half of deaths in patients with ESKD are thought to be due to CV complications. A large-scale analysis (N = 1,120,295) in a cohort not undergoing RRT found that the adjusted hazard ratio (HR) for CV events increased from 1.4 in those with eGFR of 45–59 mL/min/1.73 m 2 to 3.4 in those with eGFR of < 15 mL/min/1.73 m 2. Įven small decreases in estimated glomerular filtration rate (eGFR) are associated with an increased risk of CV events, including CV mortality. Furthermore, observational studies have identified duration of diabetes as an independent risk factor for progression of renal impairment. Similarly, in large outcomes trials evaluating angiotensin receptor blockers in people with T2D, progression of nephropathy occurred in approximately 15–27% of placebo-treated patients over 2 years, depending on the level of baseline risk. The UK Prospective Diabetes Study (UKPDS) showed annual accrual rates of approximately 2–3% for the development of microalbuminuria, transition of micro- to macroalbuminuria, and elevated plasma creatinine or need for renal replacement therapy (RRT). 1) many people with T2D already have some degree of renal dysfunction or abnormality at the time of diagnosis, and this may evolve over time, potentially leading to the development of CKD and ultimately to end-stage kidney disease (ESKD). The risk of renal disorders in T2D includes the development of multiple phenotypes of organ damage, often overlapping and ultimately progressing, similar to what occurs for cardiovascular disease (CVD) (Fig. An analysis of the US Diabetes Collaborative Registry revealed that 94% of people with T2D presented with at least one cardiovascular (CV), metabolic, or renal comorbidity, including 20% with chronic kidney disease (CKD). Renal disorders are common in type 2 diabetes (T2D), with approximately 50% of patients developing some degree of renal impairment and an increasing prevalence of both conditions over time. This review outlines the evidence that SGLT2 inhibitors may prevent the development of CKD and prevent and delay the worsening of CKD in people with T2D at different levels of renal risk. In addition, recent studies such as CREDENCE and DAPA-CKD offer a greater insight into the renoprotective effects of SGLT2 inhibitors in patients with moderate-to-severe CKD. Benefits were observed in patients across a spectrum of renal risk, but were evident also in those without renal damage, suggesting a role for SGLT2 inhibition in the prevention of CKD in people with T2D. Patient cardiovascular risk profiles did not relevantly impact the renoprotective benefits observed in these studies. Although patients in most cardiovascular outcomes trials had higher prevalence of existing cardiovascular disease compared with those normally seen in clinical practice, the proportion of patients with renal impairment was similar to that observed in a real-world context. Recent cardiovascular outcomes trials investigating sodium–glucose cotransporter 2 (SGLT2) inhibitors have suggested that these therapies have renoprotective effects distinct from their glucose-lowering action, including the potential to reduce the rates of ESKD and acute kidney injury. Even with widespread use of renin–angiotensin system blockers and tight glycemic control, a substantial residual risk of nephropathy progression remains. In many of them, chronic kidney disease (CKD) progresses over time, eventually leading to end-stage kidney disease (ESKD) requiring dialysis and conveying a substantially increased risk of cardiovascular morbidity and mortality. Approximately half of all patients with type 2 diabetes (T2D) develop a certain degree of renal impairment.

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