SGLT2 inhibitors for non-diabetic kidney disease: drugs to treat CKD that also improve glycaemia

Abstract

Sodium–glucose co-transporter-2 (SGLT2) inhibitors decreased cardiovascular (CV) events and improved renal outcomes in CV safety studies in type 2 diabetes melitus (T2DM) patients at high CV risk. Canagliflozin also improved kidney outcomes in diabetic kidney disease in the Canagliflozin and Renal Events in Diabetes and Nephropathy Clinical Evaluationtrial. More recently, the Dapagliflozin and Prevention of Adverse Outcomes in Heart Failure (DAPA-HF) trial showed that dapagliflozin improved CV outcomes in patients with HF with or without diabetes. Protection from HF in non-diabetics was confirmed for empagliflozin in the EMPagliflozin outcomE tRial in Patients With chrOnic heaRt Failure With Reduced Ejection Fraction (EMPEROR-Reduced) trial. A meta-analysis of DAPA-HF and EMPEROR-Reduced confirmed reductions in all-cause and CV death and the combined risk of CV death or worsening HF, as well as in the composite renal endpoint {hazard ratio [HR] 0.62 [95% confidence interval (CI) 0.43–0.90]} without differences based on the presence of diabetes or baseline estimated glomerular filtration rate (eGFR). Moreover, the Study to Evaluate the Effect of Dapagliflozin on Renal Outcomes and Cardiovascular Mortality in Patients With Chronic Kidney Disease (DAPA-CKD) showed that dapagliflozin as an add-on over renin–angiotensin system blockade in patients with chronic kidney disease (CKD; with or without T2DM) reduced the HR for the primary endpoint (time to the first occurrence of ≥50% eGFR decline, end-stage kidney disease or renal or CV death) to 0.61 (95% CI 0.51–0.72) and for the secondary endpoints of worsening renal function or death from kidney failure [HR 0.56 (95% CI 0.45–0.68)], hospitalization for HF or CV death [HR 0.71 (95% CI 0.55–0.92)] and all-cause mortality [HR 0.69 (95% CI 0.53–0.88)]. These beneficial effects were consistent in patients with and without T2DM. In conclusion, SGLT2 inhibitors offer CV and kidney protection in both diabetic and non-diabetic CKD and, additionally, improve glycaemic control in T2DM, making them first-line therapy for CKD independent from diabetic status.

How Do I Manage Hypertension in Patients with Advanced Chronic Kidney Disease Not on Dialysis? Perspectives from Clinical Practice

“…Dapagliflozin reduced significantly the risk of the primary combined endpoint of >50% eGFR decline, onset of ESKD or kidney or CV death with a hazard ratio of 0.61 (95% CI 0.51-0.72). 76 The renal benefits were comparable in patients with diabetic and non-diabetic kidney diseases. The impact on cardiac events and mortality were also significant.…”

Empagliflozin therapy and insulin resistance-associated disorders: effects and promises beyond a diabetic state

“…Large randomized controlled trials in diabetic and non-diabetic patients with CKD and HF have shown that SGLT2 inhibitors can slow kidney dis-ease progression, reduce cardiovascular events, and improve survival independently of the presence of diabetes [136]. Moreover, their potential use in several IR associated disorders, to improve current clinical management and ameliorate the increased cardiovascular burden, is evolving [2,3,17,137].…”

Undiagnosed cardiovascular risk factors in overweight and obese individuals: a low income country experience

“…This may be based on simple lifestyle changes (exercise, diet, stop smoking) or be further supported, once the diagnoses were confirmed, by drug therapy. Renin-angiotensin system blockade and metformin represent low cost and effective drugs for hypertension, kidney protection, diabetes treatment and weight loss ( Fernandez-Fernandez et al, 2020 ). While SGLT2 inhibitors are yet expensive, the cost is expected to significantly come down in the near future, providing additional drugs that treat type 2 diabetes while promoting weight loss, a lowering blood pressure and affording kidney and cardiac protection ( Fernandez-Fernandez et al, 2019 ).…”