Effectiveness of SGLT2 inhibitors, incretin-based therapies, and finerenone on cardiorenal outcomes: a meta-analysis and network meta-analysis
An updated meta-analysis and network meta-analysis confirms that SGLT2 inhibitors, incretin-based therapies, and finerenone each reduce cardiorenal outcomes across high-risk groups, and indirect comparisons suggest SGLT2 inhibitors may reduce heart-failure and kidney composite outcomes more than incretin-based therapies in type 2 diabetes with cardiovascular risk and in CKD.
Background
Guidelines recommend SGLT2 inhibitors, GLP-1 receptor agonists, and finerenone for cardiorenal protection in selected patients, but their relative effectiveness across populations is not well defined. This study synthesized the evidence and used a network meta-analysis to compare drug classes.
Study design
A systematic search (MEDLINE and CENTRAL, January 2023–April 2025) plus prior meta-analyses identified 33 randomized controlled trials. Random-effects models generated hazard ratios for cardiovascular mortality, all-cause mortality, heart-failure hospitalization/events, non-fatal MI, non-fatal stroke, and kidney composite outcomes across subpopulations (T2D with ASCVD/high CV risk, CKD, HFrEF, HFpEF, HFpEF with obesity, post-MI, acute HF, and obesity without diabetes). A network meta-analysis compared classes using placebo as the common comparator.
Key findings
Incretin-based therapies reduced cardiovascular and all-cause mortality, non-fatal MI, and kidney composite outcomes in CKD, and additionally reduced HF events and stroke in T2D with ASCVD; in HFpEF with obesity they reduced HF events. SGLT2 inhibitors reduced cardiovascular/all-cause mortality, HF hospitalizations, and kidney composite outcomes in HFrEF and CKD/T2D, and lowered HF hospitalizations in HFpEF, post-MI, and acute HF. Finerenone reduced HF hospitalizations and kidney composite outcomes in diabetic CKD. In indirect comparisons, SGLT2 inhibitors conferred significantly greater reductions in HF events and kidney composite outcomes than incretin-based therapies in T2D with ASCVD and in CKD.
Clinical implications
All three drug classes have a confirmed role in cardiorenal risk reduction, with benefits extending to newer populations (acute HF/post-MI for SGLT2 inhibitors; obese HFpEF for incretins). The indirect signal favoring SGLT2 inhibitors for heart-failure and kidney outcomes can help prioritize therapy, though head-to-head trials remain lacking.
Category
Research
Source
Cardiovascular Diabetology: Endocrinology Reports
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