Effects of finerenone and glucagon-like peptide 1 receptor agonists on cardiovascular and renal outcomes in type 2 diabetes mellitus: a systematic review and meta-analysis

To assess the effects of finerenone and glucagon-like peptide 1 receptor agonists (GLP1-RA) on cardiovascular and renal outcomes in patients with type 2 diabetes mellitus (T2DM), and the relative cardiovascular benefits in patients with or without established atherosclerotic cardiovascular disease for different outcomes with these classes of drugs.

We searched PubMed, the Cochrane Library, and Embase from January 1, 2000, to December 30, 2022, to identify randomized controlled trials. The primary outcomes were the composite of nonfatal myocardial infarction, nonfatal stroke, and cardiovascular death (MACE); hospitalization for heart failure (HHF); and a composite of renal outcomes. The results were reported as hazard ratios (HRs) with 95% confidence intervals (CIs).

In total, we identified 11 trials and 73,927 participants, 13,847 (18.7%) in finerenone trials and 60,080 (81.3%) in GLP1-RA trials. Finerenone reduced the risk of MACE by 13% (HR, 0.87; 95% CI, 0.79–0.95; P = 0.003), while GLP1-RA reduced the risk in a similar magnitude by 13% (HR, 0.87; 95% CI, 0.83–0.92; P < 0.001). For both drug classes, the effect on lowering the risk of MACE was restricted to approximately 14% in patients with established atherosclerotic cardiovascular disease (HR, 0.86; 95% CI, 0.82–0.90; P < 0.001), whereas no effect was observed in patients without established atherosclerotic cardiovascular disease (HR, 0.93; 95% CI, 0.85–1.02; P = 0.12). GLP1-RA reduced myocardial infarction, stroke and cardiovascular death more than finerenone (which appeared to have no effect). Only finerenone was beneficial for reducing the risk of HHF (HR, 0.78; 95% CI, 0.66–0.92; P = 0.003). Both finerenone (HR, 0.84; 95% CI, 0.77–0.92; P < 0.001) and GLP1-RA (HR, 0.81; 95% CI, 0.76–0.86; P < 0.001) reduced the risk of kidney disease progression, including macroalbuminuria, and finerenone was superior to GLP1-RA in delaying deterioration of kidney function.

Finerenone and GLP1-RA lead to a risk reduction in MACE to a similar degree in patients with established atherosclerotic cardiovascular disease. For both drug classes, the effect on lowering the risk of progression of kidney disease was also in a similar magnitude in patients with T2DM, whereas only finerenone had a significant protective effect against HHF. Treatment decisions for patients with T2DM should consider the clinical benefit profiles of each drug.