Nayana Khurana1,2, Steven James3, Melinda T Coughlan2,4,5, Richard J MacIsaac1,6, Elif I Ekinci1,2. 1. Melbourne Medical School, Department of Medicine, the University of Melbourne, Parkville, Victoria, 3010, Australia. 2. Department of Endocrinology, Austin Health, Heidelberg, Victoria, 3084, Australia. 3. School of Nursing, Midwifery and Paramedicine, the University of the Sunshine Coast, Petrie, Queensland, 4502, Australia. 4. Baker Heart and Diabetes Institute, Melbourne, Victoria, 3004, Australia. 5. Department of Diabetes, Monash University, Central Clinical School, Alfred Medical Research Education Precinct, Melbourne, 3004, Australia. 6. Department of Endocrinology & Diabetes, St Vincent's Hospital Melbourne, Fitzroy, Victoria, 3065, Australia.
Abstract
CONTEXT: The increasing burden of diabetic kidney disease (DKD) has led to the discovery of novel therapies. OBJECTIVE: This review aims to summarize the results of recent clinical trials that test the efficacy of potential therapies for DKD. METHODS: A systematized narrative review was performed utilizing the PubMed, Embase (Ovid), CINAHL, and Cochrane databases (January 2010 to January 2021). The included trials assessed the efficacy of specific medications using renal endpoints in adult participants with type 1 or 2 diabetes. RESULTS: Fifty-three trials were identified. Large, multinational, and high-powered trials investigating sodium-glucose cotransporter 2 (SGLT2) 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 need 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. CONCLUSION: Trials have yielded promising results in the search for new therapies to manage DKD. SGLT2 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.
CONTEXT: The increasing burden of diabetic kidney disease (DKD) has led to the discovery of novel therapies. OBJECTIVE: This review aims to summarize the results of recent clinical trials that test the efficacy of potential therapies for DKD. METHODS: A systematized narrative review was performed utilizing the PubMed, Embase (Ovid), CINAHL, and Cochrane databases (January 2010 to January 2021). The included trials assessed the efficacy of specific medications using renal endpoints in adult participants with type 1 or 2 diabetes. RESULTS: Fifty-three trials were identified. Large, multinational, and high-powered trials investigating sodium-glucose cotransporter 2 (SGLT2) 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 need 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. CONCLUSION: Trials have yielded promising results in the search for new therapies to manage DKD. SGLT2 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.
Authors: Piotr Dobrowolski; Aleksander Prejbisz; Alina Kuryłowicz; Alicja Baska; Paweł Burchardt; Krzysztof Chlebus; Grzegorz Dzida; Piotr Jankowski; Jerzy Jaroszewicz; Paweł Jaworski; Karol Kamiński; Agnieszka Kapłon-Cieślicka; Marek Klocek; Michał Kukla; Artur Mamcarz; Agnieszka Mastalerz-Migas; Krzysztof Narkiewicz; Lucyna Ostrowska; Daniel Śliż; Wiesław Tarnowski; Jacek Wolf; Mariusz Wyleżoł; Tomasz Zdrojewski; Maciej Banach; Andrzej Januszewicz; Paweł Bogdański Journal: Arch Med Sci Date: 2022-08-30 Impact factor: 3.707