In short: SGLT2 inhibitors, GLP-1 receptor agonists, and finerenone (a non-steroidal mineralocorticoid-receptor antagonist) are three drug classes that protect the heart and kidney together rather than treating them separately. Each is supported by large randomized trials showing reductions in kidney and/or cardiovascular events, and in appropriate patients they are increasingly used in combination for additive organ protection.
Three classes, one goal
SGLT2 inhibitors (e.g., dapagliflozin, empagliflozin) reduce chronic kidney disease progression and cardiovascular events across broad CKD populations, including patients without diabetes. GLP-1 receptor agonists (e.g., semaglutide) reduce major kidney events and cardiovascular death in type 2 diabetes with CKD, and support weight and glycaemic control. Finerenone blocks mineralocorticoid-receptor–driven inflammation and fibrosis, reducing kidney and cardiovascular events in CKD associated with type 2 diabetes.
The landmark trials
The hazard ratios below are the primary (or, where noted, key secondary) outcomes reported in each pivotal trial. A hazard ratio below 1.0 favors the drug; the figures in brackets are 95% confidence intervals.
| Trial · drug | Population | Outcome | Hazard ratio (95% CI) |
|---|---|---|---|
| DAPA-CKD · dapagliflozin | CKD with or without type 2 diabetes | ≥50% eGFR decline, kidney failure, or renal/CV death | 0.61 (0.51–0.72) |
| EMPA-KIDNEY · empagliflozin | Broad CKD population | Kidney-disease progression or CV death | 0.72 (0.64–0.82) |
| FLOW · semaglutide | Type 2 diabetes with CKD | Major kidney events (incl. renal/CV death) | 0.76 (0.66–0.88) |
| FLOW · semaglutide | Type 2 diabetes with CKD | Death from cardiovascular causes | 0.71 (0.56–0.89) |
| FIDELIO-DKD · finerenone | CKD with type 2 diabetes | Kidney failure, ≥40% eGFR decline, or renal death | 0.82 (0.73–0.93) |
| FIGARO-DKD · finerenone | CKD with type 2 diabetes | CV death, nonfatal MI, nonfatal stroke, or HF hospitalization | 0.87 (0.76–0.98) |
Finerenone’s benefit also extends to heart failure: in FINEARTS-HF, in patients with mildly reduced or preserved ejection fraction (LVEF ≥40%), it reduced total worsening–heart-failure events and cardiovascular death.
How they fit together
These classes act through different mechanisms — glucose- and sodium-handling, incretin signalling, and mineralocorticoid-receptor blockade — so their benefits are largely complementary. In line with the 2026 CKM guideline, an angiotensin-system inhibitor plus an SGLT2 inhibitor form the shared foundation for albuminuric CKD (or CKD with type 2 diabetes), with a GLP-1 receptor agonist and/or finerenone added according to the patient’s diabetes status, residual albuminuria, weight, and heart-failure phenotype.
Compare the therapies interactivelyExplore each drug class and its landmark trial side by side in the CKM Explorer therapy module.Open the CKM Explorer →Frequently asked questions
What is the difference between SGLT2 inhibitors, GLP-1 receptor agonists, and finerenone?
SGLT2 inhibitors act on kidney glucose and sodium handling and reduce CKD progression and cardiovascular events across broad populations. GLP-1 receptor agonists act through incretin signalling and reduce major kidney events and cardiovascular death in type 2 diabetes with CKD while aiding weight and glucose control. Finerenone is a non-steroidal mineralocorticoid-receptor antagonist that reduces mineralocorticoid-driven inflammation and fibrosis, lowering kidney and cardiovascular events in CKD with type 2 diabetes.
Can these organ-protective drugs be combined?
Yes. Because the three classes work through different mechanisms, their benefits are largely complementary, and in appropriate patients they are increasingly combined for additive heart and kidney protection under specialist guidance.
Which trials support these therapies?
Key trials include DAPA-CKD and EMPA-KIDNEY for SGLT2 inhibitors, FLOW for semaglutide, FIDELIO-DKD and FIGARO-DKD for finerenone in CKD with type 2 diabetes, and FINEARTS-HF for finerenone in heart failure with mildly reduced or preserved ejection fraction.
Do SGLT2 inhibitors work in people without diabetes?
Yes. DAPA-CKD and EMPA-KIDNEY included patients with chronic kidney disease with or without type 2 diabetes and showed reductions in kidney and cardiovascular outcomes across the population.
References
- Heerspink HJL, et al. Dapagliflozin in Patients with Chronic Kidney Disease (DAPA-CKD). N Engl J Med. 2020. doi:10.1056/NEJMoa2024816
- The EMPA-KIDNEY Collaborative Group. Empagliflozin in Patients with Chronic Kidney Disease (EMPA-KIDNEY). N Engl J Med. 2023. doi:10.1056/NEJMoa2204233
- Perkovic V, et al. Effects of Semaglutide on Chronic Kidney Disease in Type 2 Diabetes (FLOW). N Engl J Med. 2024. doi:10.1056/NEJMoa2403347
- Bakris GL, et al. Effect of Finerenone on Chronic Kidney-Disease Outcomes in Type 2 Diabetes (FIDELIO-DKD). N Engl J Med. 2020. doi:10.1056/NEJMoa2025845
- Pitt B, et al. Cardiovascular Events with Finerenone in Kidney Disease and Type 2 Diabetes (FIGARO-DKD). N Engl J Med. 2021. doi:10.1056/NEJMoa2110956
- Solomon SD, et al. Finerenone in Heart Failure with Mildly Reduced or Preserved Ejection Fraction (FINEARTS-HF). N Engl J Med. 2024. doi:10.1056/NEJMoa2407107
- 2026 AHA/ACC/ADA/ASN Guideline for the Prevention, Detection, Evaluation, and Management of Cardiovascular-Kidney-Metabolic Syndrome. J Am Coll Cardiol. 2026. doi:10.1016/j.jacc.2026.03.056
Educational use only. This page explains concepts for health professionals, trainees, and students. It is not medical advice and does not calculate an individual patient’s risk.