Effects of SGLT2is on kidney outcomes across subpopulations with HF, CKD, and/or T2D

27/11/2024

In a large systematic review and meta-analysis, SGLT2 inhibitors reduced the risk of adverse kidney outcomes compared with placebo in patients with HF, CKD, T2D, or a combination thereof.

This summary is based on the publication of Siddiqi TJ, Cherney D, Siddiqui HF, et al. - Effects of Sodium-Glucose Cotransporter-2 Inhibitors on Kidney Outcomes across Baseline Cardiovascular-Kidney-Metabolic Conditions: A Systematic Review and Meta-Analyses. J Am Soc Nephrol. 2024 Sep 4 [Online ahead of print]. doi: 10.1681/ASN.0000000000000491

Introduction and methods

Background

Several trials have demonstrated the beneficial effects of SGLT2 inhibitors on kidney outcomes in patients with T2D, HF, or CKD [1-10]. Often, patients exhibit a complex interplay of these 3 diseases, which greatly influences their prognosis. To guide personalized treatment decisions, the therapeutic effects within these subpopulations and in various combinations of multimorbidity need to be understood. However, individual studies lack statistical power and previous meta-analyses did not include different combinations of the 3 conditions [11-13].

Aim of the study

In a systematic review and study-level data meta-analysis, the authors assessed the effects of SGLT2 inhibitors on kidney outcomes in specific subpopulations characterized by the presence of various combinations of HF, CKD, and T2D at baseline.

Methods

The authors performed a systematic literature search in PubMed and Scopus to identify primary and secondary analyses of relevant placebo-controlled RCTs of the efficacy of SGLT2 inhibitors with regard to kidney outcomes in patients with HF, CKD, and/or T2D published until March 2024 . This resulted in 11 included trials (n=80,928). Effect sizes were pooled using the generic inverse variance method and random-effects model.

Outcomes

The endpoints were a composite kidney outcome (defined as eGFR <15 mL/min/1.73 m², sustained doubling of serum creatinine level, varying percent change in eGFR, or need for kidney replacement therapy), rate of eGFR slope decline, and albuminuria progression.

Main results

  • In the overall study population, treatment with SGLT2 inhibitors versus placebo reduced the risk of the composite kidney outcome (HR: 0.67; 95%CI: 0.59–0.75; I²=61%; τ²=0.03), promoted regression of albuminuria (HR: 1.50; 95%CI: 1.32–1.70; I²=82%; τ²=0.02), reduced the risk of sustained doubling of the serum creatinine level (HR: 0.64; 95%CI: 0.56–0.72; I²=6%; τ²=0.00), slowed the annual rate of eGFR slope decline (mean difference: 1.16 mL/min/1.73 m² per year; 95%CI: 1.08–1.24; I²=90%) , and reduced progression of albuminuria (HR: 0.65; 95%CI: 0.57–0.76; I²=86%; τ²=0.02).
  • In patients with HFrEF (i.e., LVEF ≤40%), SGLT2 inhibitor use decreased the risk of the composite kidney outcome compared with placebo (HR: 0.59; 95%CI: 0.42–0.83; I²=9%; τ²=0.01) but not in patients with HFpEF (HR: 0.87; 95%CI: 0.63–1.21; I²=62%; τ²=0.05). The difference in treatment effects was not statistically significant (Χ²=3.72; P=0.05).
  • In patients with T2D, SGLT2 inhibitors reduced the risk of the composite kidney outcome compared with placebo (HR: 0.62; 95%CI: 0.56–0.69; I²=32%; τ²=0.01) and promoted regression of albuminuria (HR: 1.42; 95%CI: 1.20–1.69; I²=75%; τ²=0.02).
  • Compared with placebo, SGLT2 inhibitors also decreased the risk of the composite kidney outcome in patients with CKD (HR: 0.64; 95%CI: 0.55–0.73; I²=40%; τ²=0.01).
  • Overall, similar patterns for the beneficial effects of SGLT2 inhibitors over placebo were observed in subpopulations with different combinations of multimorbidity, as well patients with no HF, CKD, or T2D.

Conclusion

In this systematic review and meta-analysis among >80,000 patients with HF, CKD, and/or T2D, the use of SGLT2 inhibitors reduced the risk of the composite kidney outcome, slowed the rate of eGFR slope decline, and reduced progression of albuminuria compared with placebo. Overall, the beneficial effects of SGLT2 inhibitors were consistent across subpopulations with different combinations of multimorbidity, as well as patients with none of these comorbidities.

Find this article online at J Am Soc Nephrol.

References

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