Sodium-glucose cotransporter 2 inhibitors (SGLT2i) have been used as anti-hyperglycemic drugs in patients with type 2 diabetes. However, beyond its glucose-lowering effects, evidence is fast accumulating in favor of SGLT2i becoming a standard of care in patients with heart failure. A meta-analysis of randomized controlled trials published in the January 2023 issue of the journal Clinical Research in Cardiology provides further evidence urging their use in heart failure patients.¹

A team of researchers from Brazil and the United States conducted a meta-analysis of 9 studies involving 2824 patients with acute heart failure. Through this meta-analysis, they sought to compare cardiovascular and renal outcomes in 1411 patients who received SGLT2i in addition to conventional diuretic therapy (intervention group) and 1413 patients who received diuretic therapy alone (control group).

Pooled analysis revealed that the addition of SGLT2i to standard therapy of patients with acute heart failure reduced all-cause mortality rate with odds ratio of 0.75. Rehospitalizations for heart failure also declined with OR 0.54. The composite of cardiovascular death and readmissions for HF decreased as well with hazard ratio 0.71. These beneficial effects of SGLT2i were seen to persist in a sensitivity analysis after follow-up of 1–12 months including in a time-to-event sensitivity analysis calculating hazard ratios. Results of a subgroup analysis of only placebo-controlled studies were also supportive of the positive effects of SGLT2i similar to the pooled analysis.

Assessment of renal function showed a marked increase in the mean daily urinary output (MD 0.45 liters) in the intervention group compared to the control group. The SGLT2i-treated patients also had significantly lower daily doses of loop diuretics (MD -34.90 mg of furosemide equivalent). No worsening of renal function was observed (OR 0.75) with the addition of SGLT2i.

The incidence of worsening renal function was also less in a sensitivity analysis of studies defining worsening renal function as an increase ≥ 0.3 mg/dL of serum creatinine level.

In a subgroup analysis of only placebo-controlled trials, similar results were observed in the frequency of worsening renal function (OR 0.70).

The reduction in all-cause mortality, rehospitalizations and daily dose of loop diuretics during hospital stay along with increase in daily urinary output suggest a role for SGLT2i in the treatment of inpatients in acute heart failure as add-on to the conventional diuretic therapy. The diuretic and natriuretic effects of SGLT2i via inhibition of sodium and glucose absorption from the proximal tubule come into play in such cases.

Reference

1. Carvalho PEP, et al. Cardiovascular and renal effects of SGLT2 inhibitor initiation in acute heart failure: a meta-analysis of randomized controlled trials. Clin Res Cardiol. 2023 Jan 2;1-12. doi: 10.1007/s00392-022-02148-2.