Table 1.

The Selected Landmark Achievements of the Clinical Trials in Diabetic Kidney Disease.

Name of the Trials	Tested Drugs	Brief Description of the Trial	Renal Outcomes	Ref.
SGLT2 Inhibitor
CREDENCE	Canaglifozin	Patients recruited: 4,401 (690 sites, 34 countries); Median Follow-up:2.62years; eGFR:30 to <90 ml/min/1.73 m2; Urinary Albumin/Creatinine Ratio (UACR): 300–5000 mg/g; HbA1c:6.5–12%; Established cardiovascular disease; Treated with RAS blocker.	30% lower relative risk of the primary outcome (a composite of ESRD, a doubling of the serum creatinine level, or death from renal or cardiovascular causes): 43.2 vs. 61.2 per 1000 patient-years	[132]
EMPA-REG OUTCOME	Empaglifozin	Patients recruited: 7,020 (590 sites, 42 countries); Median duration of treatment: 2.6 years; Median observation time: 3.1 years; eGFR:≥30 ml/min/1.73 m2; Established cardiovascular disease.	39% relative risk reduction of incident or worsening nephropathy:12.7% vs. 18.8%; 38% relative risk reduction of progression to macroalbuminuria:11.2% vs. 16.2%; 44% relative risk reduction of doubling of Scr: 1.5% vs. 2.6%; 55% lower relative risk in replacement therapy: 0.3% vs. 0.6%.	[136]
GLP-1 Receptor Agonist
LEADER	Liraglutide	Patients recruited: 9,340; Median Follow-up:3.84years; eGFR: ≥30 ml/min/1.73 m2; A high risk of cardiovascular disease.	Lower incidents of the renal outcome (new-onset persistent macroalbuminuria, persistent doubling of the Scr level and eGFR of 45 ml or less per min/1.73 m2, need renal-replacement therapy, or death):5.7% vs. 7.2%; New-onset persistent macroalbuminuria: 3.4% vs. 4.6%; eGFR decline:7.44 vs. 7.82 ml/min/1.73 m2.	[137]
AWARD-7	Dulaglutide	Patients recruited: 577 (99 sites, 9 countries); Duration of treatment: 52 weeks; HbA1c:7.5–10.5%; Moderate-to-severe CKD; Treated with insulin or insulin plus an oral antihyperglycemic drug, RAS blocker, GLP-1 receptor agonist or DPP4 inhibitor.	HbA1c-lowering effects persisted to 52 weeks; eGFR was higher at 52 weeks; No significant difference on UA reduction.	[130]
Dipeptidyl Peptidase 4 (DPP-4) Inhibitor
CARMELINA	Linagliptin	Patients recruited: 6,979 (605 sites, 27 countries); Median Follow-up:2.2years; HbA1c:7.5–10.5%; High CV risk and renal risk.	No significant difference in kidney composite outcome: 9.4% vs. 8.8%.	[165]
SAVOR-TIMI 53	Saxagliptin	Patients recruited: 16,492 (25 countries); Median Follow-up:2.1years; HbA1c:6.5–12%; Established cardiovascular disease.	Improvement in and/or less deterioration in ACR, without affecting eGFR.	[166]
Selective Endothelin Receptor Antagonist
SONAR	Atrasentan	Patients recruited: 2,648 (689 sites, 41 countries); Median Follow-up:2.2years; eGFR:25–75 ml/min/1.73 m2; Urinary Albumin/Cr: 300–5000 mg/g; Treated with RAS blocker at least 4 weeks.	Lower primary composite renal endpoint event: 6.0% vs. 7.9%;	[167]