Pharmacokinetics of novel drugs for the treatment of Diabetic nephropathy

INTRODUCTION: Diabetic kidney disease (DKD) alters drug pharmacokinetics (PK), affecting exposure, pharmacodynamic response, and toxicity. As newer therapies become central to DKD management, understanding their PK profiles is essential for individualized treatment across stages of kidney impairment. AREAS COVERED: PubMed/MEDLINE, Embase, and Scopus were searched from database inception through 18 April 2026, for evidence on PK, pharmacodynamics, renal-impairment effects, and drug-drug interactions. Evidence was synthesized for sodium-glucose cotransporter-2 inhibitors (SGLT2i), glucagon-like peptide-1 receptor agonists (GLP-1RA), dual incretin agonists, nonsteroidal mineralocorticoid receptor antagonists (nsMRA), endothelin receptor antagonists (ERA), aldosterone synthase inhibitors (vicadrostat, baxdrostat, and lorundrostat), avenciguat, and ziltivekimab, emphasizing exposure, clearance, metabolism, elimination, and dosing implications. EXPERT OPINION: In reduced kidney function, SGLT2i show modest exposure increases but attenuated glucose-lowering effects, finerenone shows modest exposure increases despite minimal renal clearance, and ERA may have larger increases that narrow the therapeutic window. Newer incretin therapies generally maintain stable exposure, while eGFR alone may incompletely capture PK risk because uremia, altered protein binding, and nonrenal clearance can influence exposure. The next advance is likely to be drug-specific decision support integrating estimated glomerular filtration rate trajectory, potassium, dialysis status, body composition, and interacting medications, rather than universal therapeutic drug monitoring.