This systematic review and meta-analysis of real-world observational studies assessed the renoprotective effects of SGLT2 inhibitors in people with type 2 diabetes, in order to determine whether the benefits seen in clinical trials extended to broader populations treated in routine clinical practice, including in people without chronic kidney disease (CKD) at treatment initiation. A total of 34 studies, with a pooled population of 1 494 373 adults with diabetes, were analysed.
The primary outcome was a standardised composite of kidney failure events, comprising kidney transplantation, haemodialysis, death from kidney failure, sustained eGFR decline or a sustained eGFR of <15 mL/min/1.73 m2. Meta-analysis showed that, compared with other glucose-lowering therapies as a whole, SGLT2 inhibitor use reduced the risk of this composite outcome by 46% (HR, 0.54; 95% CI, 0.47–0.63). The absolute risk reduction was 6.4 kidney failure events per 1000 person-years, such that 156 people would need to be treated to prevent one kidney failure event per year.
The renal benefits of SGLT2 inhibitors were independent of CKD status at baseline and were consistent across various categories of eGFR, including in people with an eGFR of ≥90 mL/min/1.73 m2 and those with eGFR <60 at treatment initiation. Similarly, the benefits were independent of albuminuria category and extended to those without albuminuria at baseline. SGLT2 inhibitors were associated with a 15% lower risk of new-onset albuminuria.
SGLT2 inhibitors were associated with a 50% lower risk of kidney failure when compared with DPP-4 inhibitors and a 49% lower risk when compared with a combination of other diabetes drug classes. However, there was no significant difference in risk when compared with GLP-1 receptor agonists (HR, 0.93; 95% CI, 0.80–1.09).
The authors highlight the substantial heterogeneity across the reviewed studies, which is a recognised limitation when combining large observational studies. Most studies had a moderate degree of bias, mostly in the confounding domain, and there may have been publication bias in which only positive results were published, which may have overestimated the benefit of SGLT2 inhibitors. However, the authors conducted a number of sensitivity analyses, which did not alter their results.
Therefore, the authors conclude that the renoprotective benefits of SGLT2 inhibitors extend to the broader population of people with type 2 diabetes who are treated in routine clinical practice, including those at lower risk of kidney events with normal eGFR and without albuminuria. The findings support the recent updates to national and international guidelines which recommend SGLT2 inhibitors as renoprotective agents for use in the wider population with type 2 diabetes.