SGLT-2I–MRA combo yields maximal kidney, cardiovascular protection in T2DM, CKD

Sodium-glucose cotransporter-2 inhibitors (SGLT-2Is) confer the greatest reduction in kidney and cardiovascular risks in patients with type 2 diabetes mellitus (T2DM) and chronic kidney disease (CKD), according to a study.

Researchers conducted a systematic review of studies in which the comparative efficacy and safety of promising nephroprotective drugs, such as SGLT-2Is, glucagon-like peptide-1 receptor agonists (GLP-1RAs), dipeptidyl-peptidase IV Inhibitors (DPP-4Is), MRAs, endothelin receptor antagonist (ERAs), pentoxifylline (PTF), and pirfenidone (PFD), were evaluated in relation to cardiovascular and kidney outcomes in T2DM and CKD population.

Multiple online databases were searched, yielding 2,589 citations. A total of 27 trials, which involved 50,237 patients, met the inclusion criteria and were included in the network meta-analysis. The quality of evidence across the studies were moderate to high.

Pooled data showed that for kidney outcomes, SGLT-2Is were the best at reducing the risk of composite kidney events (risk ratio [RR], 0.69, 95 percent confidence interval [CI], 0.61–0.79) and slowing the estimated glomerular filtration rate (eGFR) slope (mean difference [MD], 1.34, 95 percent CI, 1.06–1.62). Other top-ranked drugs were MRAs (RR, 0.77, 95 percent CI, 0.68–0.88; MD, 1.31, 95 percent CI, 0.89–1.74), GLP-1RAs (RR, 0.78, 95 percent CI, 0.62–0.97; MD, 0.75, 95 percent CI, 0.46–1.05), and ERAs (RR, 0.75, 95 percent CI, 0.57–0.99; MD, 0.7, 95 percent CI, 0.3–1.1).

For cardiovascular outcomes, SGLT-2Is also ranked first for lowering the risk of heart failure hospitalization (RR, 0.67, 95 percent CI, 0.57–0.78), followed by GLP-1RAs (RR, 0.73, 95 percent CI, 0.55–0.97) and MRAs (RR, 0.79, 95 percent CI, 0.67–0.92).

Of note, SGLT-2Is and GLP-1RAs had comparable effects on the risk of major adverse cardiovascular events (RR, 0.80, 95 percent CI, 0.71–0.89 and RR, 0.72, 95 percent CI, 0.60–0.86, respectively). MRAs showed a potential association with increased drug discontinuation due to adverse events (RR, 1.21, 95 percent CI, 1.05–1.38).

For the hyperkalemia outcome, SGLT-2Is had a protective effect (RR, 0.78, 95 percent CI, 0.65–0.93), whereas MRAs were associated with a risk increase (RR, 2.08, 95 percent CI, 1.86–2.33).