Table 1.
Review of drugs for DKD treatments
| Categories | Drugs | Studies | Outcomes/status |
|---|---|---|---|
| Newly approved drugs | |||
| SGLT2 inhibitor | Empagliflozin | NCT01392560 (clinicaltrials.gov) Wanner et al. [63], 2016 | Attenuate renal hyperfiltration in subjects with type 1 diabetes Slower progression of kidney disease |
| Canagliflozin | Perkovic et al. [64], 2019 Heerspink et al. [65], 2017 |
Significantly lower risk of kidney failure Slower the progression of renal disease over 2 years in type 2 diabetes |
|
| Dapagliflozin | Dekkers et al. [66], 2018 NCT02413398 (clinicaltrials.gov) |
6 weeks of dapagliflozin decrease albuminuria and eGFR Decrease from baseline in eGFR is greater with dapagliflozin than placebo at week 24 but eGFR return to baseline levels at week 27 |
|
| Promising drugs in phase III clinical trials | |||
| GLP-1 analog | Liraglutide | Marso et al. [68], 2016 Mann et al. [69], 2017 |
Lower rate of new onset of persistent macroalbuminuria and progression of DKD |
| Semaglutide | Marso et al. [70], 2016 | Lower rates of new or deteriorating nephropathy | |
| Endothelin-1 receptor A antagonist | Avosentan | Mann et al. [75], 2010 | Reduce urinary albumin excretion Terminated early because of excessive cardiovascular events |
| Atrasentan | de Zeeuw et al. [76], 2014 | Had a proteinuria-lowering effect Terminated early due to the recruitment issue | |
| MRA | Apararenone (MT−3995) | NCT02676401 (clinicaltrials.gov) | Ongoing in Japan |
| Esaxerenone | Kolkhof et al. [78], 2017 | In phase II and III randomized clinical trial | |
| Finerenone | Pitt et al. [79], 2013 Bakris et al. [80], 2015 NCT02540993 (clinicaltrials.gov) NCT 02545049 (clinicaltrials.gov) |
Reduce albuminuria Reduce albuminuria in a dose-dependent manner Ongoing Ongoing |
|
| Antifibrotic therapy | Pirfenidone | Sharma et al. [24], 2011 NCT02689778 (clinicaltrials.gov) |
Have an mean increase of eGFR after 1 year of therapy in 1,200 mg/d Ongoing |
| Pentoxifylline | Navarro-Gonzalez et al. [83], 2015 NCT03625648 NCT03664414 (clinicaltrials.gov) |
Reduce albuminuria, slow progression of renal disease in patients with type 2 diabetes and stages 3-4 CKD Ongoing Ongoing |
|
| Potential drugs required further validations | |||
| Anti-AGE drugs | Pyridoxamine | Williams et al. [84], 2007 | Not provide a significant renal protection in DKD patients |
| JAK-STAT inhibitor | Baricitinib | Tuttle et al. [85], 2018 | A phase II clinical trial showed a reduction of proteinuria |
| Nrf2 activator | Bardoxolone methyl | Pergola et al. [23], 2011 de Zeeuw et al. [90], 2013 |
Have no influence of albuminuria Increase the GFR in patients with type 2 DM Phase III clinical study was terminated early because of more cardiovascular events |
| Nox1/4 inhibitor | GKT137831 APX-115 | Gorin et al. [92], 2015 Cha et al. [94], 2017 |
A beneficial effect in murine models of DN A renal protective effect in an experimental animal model of diabetes |
| Inhibitor of chemokines cytokines | NOX-E36 | Boels et al. [95], 2017 Menne et al. [96], 2017 |
A reduction in albuminuria in mouse models A phase II clinical trial demonstrated a reduced albuminuria in patients with T2DM and DN |
SGLT2, sodium-glucose co-transporter-2; GLP-1, glucagon-like peptide-1; MRA, mineralocorticoid receptor antagonists; AGE, advanced glycation end products; JAK-STAT, janus kinase/signal transducer and activator of transcription; Nrf2, nuclear factor-2; Nox1/4, NADPH oxidase; DKD, diabetic kidney disease; GFR, glomerular filtration rate; CKD, chronic kidney disease; DN, diabetic nephropathy; T2DM, type 2 diabetes mellitus.