SGLT2 inhibitors for the prevention of kidney failure in patients with type 2 diabetes: a systematic review and meta-analysis

Abstract

This review summarises data from four studies including 38,723 participants across six continents.There was clear evidence that SGLT2 inhibitors reduce the risk dialysis, transplantation or death due to kidney disease, as well as a range of other major kidney outcomes, and that these agents also provide protection against acute kidney injury. Additionally, there were definitive, separate benefits at all levels of kidney function, including an approximate 30% proportional risk reduction in the composite kidney outcome in participants with baseline eGFR less than 45 mL/min/1•73m 2 in whom these drugs are mostly not permitted for use. Implications of all the available evidenceThese results provide the strongest evidence yet that SGLT2 inhibitors should be routinely offered to individuals with type 2 diabetes at risk of progressive kidney disease. The clear evidence of renoprotection across the spectrum of kidney function studied to date call into question current restrictions on the use of SGLT2 inhibitors in people with reduced kidney function, and suggest that many more individuals with type 2 diabetes at high risk of kidney failure are likely to benefit from treatment.

Interplay of adenosine monophosphate‐activated protein kinase/sirtuin‐1 activation and sodium influx inhibition mediates the renal benefits of sodium‐glucose co‐transporter‐2 inhibitors in type 2 diabetes: A novel conceptual framework

“…The mechanisms by which SGLT2 inhibitors preserve renal function in patients with diabetes have not been established, but the effect cannot be attributed to a glucose‐lowering action of these drugs. Intensive glycaemic control over 5–10 years has been shown to prevent the development of macroalbuminuria in patients with diabetes, but SGLT2 inhibitors have been shown to reduce the risk of end‐stage renal disease after only 2–3 years of treatment . Comparable or greater decreases in blood glucose produced by glucagon‐like peptide‐1 receptor agonists and dipeptidyl peptidase‐4 inhibitors administered for similar or longer periods of time are accompanied by no or only small benefits on the rate of decline in glomerular function and no reduction in the risk of major adverse renal outcomes, despite a decrease in albuminuria .…”

“…By contrast, SGLT2 inhibitors have been hypothesized to decrease glomerular hyperfiltration by promoting afferent arteriolar vasoconstriction . Potentially because they act in complementary ways, SGLT2 inhibitors exert favourable effects on the diabetic kidney in patients who are already receiving inhibitors of the renin‐angiotensin system …”

“…Large‐scale, randomized, double‐blind, placebo‐controlled trials have shown that sodium‐glucose co‐transporter 2 (SGLT2) inhibitors slow the progressive loss of renal function in patients with diabetes . SGLT2 inhibitors reduce the risk of end‐stage renal events, including the occurrence of renal death and the need for dialysis or renal transplantation by 30%–35% . These benefits are seen in patients with preserved or impaired pretreatment renal function and have been reported with several members of the drug class, although only one trial with canagliflozin (CREDENCE) was specifically designed to show a favourable effect on renal outcomes …”

Preventing major adverse cardiovascular events by SGLT-2 inhibition in patients with type 2 diabetes: the role of kidney

“…Pooled summary estimates were calculated according to the random effects model, using the empirical Bayes method that, in Stata software, corresponds to the Paule-Mandel method [7]. In subgroup analysis, p-heterogeneity value lower than 0.1 was considered to reflect a high likelihood of difference beyond that expected by chance [8]. All analyses were done with Stata, version 16.0 (Stata Corp., College Station, TX).…”

Clinical Influence of Sodium-Glucose Cotransporter 2 (SGLT2) Inhibitors for Cardiovascular and Renal Points of View

“…As to the effects of SGLT2 inhibitors in renal failure, there was a systematic review and meta-analysis of randomized, controlled, cardiovascular or kidney outcome trials [14]. From data of 2085 records, four studies had met the inclusion criteria.…”