Novel drug may introduce new avenue for diabetes treatment

Type 2 diabetes is the primary contributing risk factor for chronic kidney disease (CKD), which develops in approximately 40% of patients with diabetes. Historically, treatment options diabetic-induced CKD have included a narrow list agents, mainly ACE inhibitors and ARBs, slow progression tissue fibrosis. However, very recently, medical community has seen potential surge new applications drugs preventing progression, despite development novel agents that target diabetic pathology specifically. Results from Phase III clinical trial agent finerenone, published October 2020 issue New England Journal Medicine, set promising stage favorable outcomes type Molecularly, finerenone dihydropyridine (DHP) does not steroid homology, like spironolactone. Pharmacists may recall this makes drug similar structure to peripheral calcium channel blockers, such as amlodipine. finerenone's therapeutic effect result vasodilation, but selective inhibition mineralocorticoid receptor, ultimately resulting aldosterone antagonism. Although preliminary evidence use traditional receptor antagonists (MRAs) yet yielded hard benefit, insights surrogate over years given hope. A meta-analysis American Kidney Diseases, example, observed 30% reduction proteinuria when MRAs, spironolactone, were added regimen or ARBs. In addition, recent review pathophysiology International suggested MRAs mitigate proinflammatory processes CKD-associated hyperaldosteronism—such reducing local increases reactive oxygen species inflammatory cytokines—that contribute fibrosis failure. Indeed, Nephrology indicated benefit extend nonsteroidal finerenone. Traditional nicely investigate most MRA date. While offer their structural similarity hormones can cause collateral damage long-term use, gynecomastia, erectile dysfunction, hyperglycemia. Conversely, unique DHP conveys more binding minimal metabolic hormonal adverse effects. JAMA 2015 suggest lesser degree hyperkalemia compared Remarkably, data Medicine FIDELIO-DKD, trial, demonstrated receiving had statistically significant 18% relative composite outcome renal failure, glomerular function decrease (40% baseline), disease–related mortality after median follow-up 2.6 years, on standard-of-care ACE/ARB therapy. time-to-event analysis revealed cardiovascular events just 1 month began. The results FIDELIO-DKD trials are encouraging raised further questions about efficacy existing agents—SGLT2 steroidal primarily. “Finerenone distinctly different, only SGLT2 inhibitors, its cousins, spironolactone eplerenone,” said George Bakris, MD, lead investigator video statement Managed Care. reduces albuminuria same extent SGLT2s.” He went note slowing disease, however, was similar, quite good SGLT2s. Bakris hypothesized could be lack exclusion taking SGLTs within trial. “Unfortunately, numbers too small you look at make whether there additivity synergy between two compounds,” Bakris. other investigating eagerly anticipated. still infancy needed, one thing certain: strategies tackling been long overdue.