Aim/Purpose: The purpose of this clinical research article is to determine if there are comparable alternatives to industry-standard or gold-standard renin-angiotensin system (RAS) blockade for diabetic nephropathy (DN) prevention or delayed progression when RAS blocking agents are contraindicated or not tolerated.

Method: A PubMed literature search was conducted utilizing search terms including diabetic nephropathy unaccompanied and in combination with sodium-glucose co-transporter 2 (SGLT2) inhibitor, glucagon-like peptide 1 (GLP1) receptor agonist, calcium channel blocker (CCB), mineralocorticoid receptor antagonist (MRA) and RAS blockade or blocker. PubMed search filters included full-text articles and article submissions no greater than 5 years from approximately February to June of 2022.

Results: Evidence supporting alternative agents to RAS blockade for DN prevention and delay is based on numerous randomized-controlled trials (RCT) and meta-analyses of these and other trials.

Conclusion: Emerging data/literature support comparable alternative therapeutics to RAS blockade for prevention and delayed progression of DN including SGLT2 inhibitors, GLP1 receptor agonists, and non-dihydropyridine CCBs. Based on the contained research, promising data are emerging supporting renoprotective benefits of CCBs, SGLT2 inhibitors, and GLP1 receptor agonists in type II diabetes patients, along with CCBs and SGLT2 inhibitors in type I diabetes patients. In limited circumstances, these benefits may be comparable to RAS blockade and suitable alternatives that are worth implementing in other circumstances, with the potential for promising data still to come. The medical community is in need of more research on both adjunct MRA therapy or MRA monotherapy for the prevention and delayed progression of DN in both type I and type II diabetes patients, though current evidence is promising.