Novel Therapies for Kidney Disease in People with Diabetes.

Abstract

The increasing burden of diabetic kidney disease (DKD) has led to the discovery of novel therapies. This review aims to summarise the results of recent clinical trials that test the efficacy of potential therapies for DKD. A systematised narrative review was performed utilising PubMed, Embase (Ovid), CINAHL and Cochrane databases (January 2010-January 2021). Trials included assessed the efficacy of specific medications using renal endpoints in adult participants with either type 1 or 2 diabetes. 53 trials were identified. Large, multinational and high-powered trials investigating sodium-glucose cotransporter-2 inhibitors demonstrated improved renal outcomes, even in patients with established DKD. Trials examining incretin-related therapies also showed some improvement in renal outcomes. Additionally, mineralocorticoid-receptor antagonists exhibited potential with multiple improved renal outcomes in large trials, including those involving participants with established DKD. Atrasentan, baricitinib, ASP8232, PF-04634817, CCX140-B, atorvastatin, fenofibrate, probucol, doxycycline, vitamin D, omega-3 fatty acids, silymarin, turmeric, total glucosides of paeony and tripterygium wilfordii Hook F extract were all associated with some improved renal endpoints, but with need for further exploration. While bardoxolone methyl was associated with a decrease in albuminuria, high rates of cardiovascular adverse effects curtailed further exploration into this agent. Selonsertib, allopurinol, praliciguat, palosuran, benfotiamine and diacerein were not associated with improved renal outcomes. Trials have yielded promising results in the search for new therapies to manage DKD. Sodium-glucose cotransporter-2 inhibitors and incretin-related therapies have demonstrated benefit and were associated with improved cardiovascular outcomes. Mineralocorticoid-receptor antagonists are another class of agents with increasing evidence of benefits.