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Abstract
Diabetic kidney disease drug development faces significant challenges, with many agents failing to improve kidney outcomes despite strong mechanistic rationale.
- Standard care for diabetic kidney disease has evolved to include therapies targeting the renin-angiotensin-aldosterone system and sodium-glucose cotransporter 2 inhibitors.
- Several drug candidates have faced failures in translating preclinical success to meaningful clinical benefits, often due to issues like hyperkalaemia and acute kidney injury.
- Examples of successful therapies include SGLT2 inhibitors, finerenone, and semaglutide, while others like dual RAAS blockade and endothelin receptor antagonists have not succeeded.
- Key challenges in development include human target validation, translating animal studies to humans, and selecting appropriate pharmacodynamic biomarkers.
- A proposed de-risking framework emphasizes the importance of human tissue evidence and biology-guided patient selection to improve future outcomes.
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