SGLT2 inhibition reduces risk for kidney outcomes in T2DM patients
SGLT2 inhibitors for the prevention of kidney failure in patients with type 2 diabetes: a systematic review and meta-analysis
Introduction and Methods
SGLT2 inhibitors have been associated with promising effects on albuminuria and creatinine-based kidney outcomes in patients with type 2 diabetes (T2DM) [1-6]. The randomized trials that reported these results were primarily designed to study the effect of SGLT2 inhibitors on CV outcomes. In these trials, only few participants were at high risk of adverse kidney outcomes. Therefore, the effect of SGLT2 inhibitors in T2DM patients at high risk of kidney disease has remained unclear. Recently, the results of the CREDENCE trial were presented. This trial was specifically designed to assess the effect of the SGLT2 inhibitor canagliflozin on a primary kidney outcome in patients with T2DM .
This systematic review and meta-analysis included four randomized, controlled trials that evaluated effects of SGLT2 inhibition on kidney outcomes in T2DM patients. All studies compared a SGLT2 inhibitor with a placebo. Three different SGLT2 inhibitors were studied in the included trials, namely empagliflozin (EMPA-REG OUTCOME), canagliflozin (CANVAS Program and CREDENCE), and dapagliflozin (DECLARE–TIMI 58). Data from in total 38723 patients were analyzed.
The primary outcome was the composite of chronic dialysis, kidney transplantation, or death due to kidney disease. The consistency of effect size across these trials was determined. The effect size on different levels of albuminuria, eGFR and use of RAS blockers was also assessed.
- Risk of dialysis, transplantation, or death due to kidney disease was reduced by SGLT2 inhibitor treatment by 33% compared to placebo. This effect was consistent across the four assessed studies (I2=0%, Pheterogenicity=0.53).
- SGLT2 inhibition reduced risk of end-stage kidney disease by 35% and risk of substantial loss of kidney function, end-stage kidney disease, or death due to kidney disease was reduced by 42%. No differences in treatment effect were found between the assessed studies (I2=0.0%, Pheterogenicity=0.41 and I2=0.0%, Pheterogenicity=0.49, respectively).
- Risk of acute kidney injury was reduced by 25%, no differences between studies were found (I2=0%, Pheterogenicity=0.68).
- Although some evidence was found that the benefit of SGLT2 inhibitor treatment attenuated across progressively lower eGFR subgroups (Ptrent=0.073), significant risk reduction of major kidney outcomes was found in all eGFR subgroups. In patients with a baseline eGFR of <45 mL/min per 1.73 m², a relative risk reduction of 30% was found with SGLT2 inhibitor treatment.
- Effect of the SGLT2 inhibitor treatment was consistent irrespective of use of RAS blockage-base treatment at baseline (Pheterogenicity=0.31) and baseline albuminuria (Ptrent=0.66).
This meta-analysis shows that SGLT2 inhibition reduces risk of dialysis, kidney transplantation, or death due to kidney disease by 33% in patients with T2DM. Renoprotection was achieved at all eGFR baseline levels, even in patients with an eGFR lower than 45 mL/min per 1.73 m². The results presented in this meta-analysis suggest that a broader population of T2DM patients at high risk of kidney disease may benefit from SGLT2 inhibition.