Beyond glycemic control: Roles for sodium-glucose cotransporter 2 inhibitors and glucagon-like peptide-1 receptor agonists in diabetic kidney disease

Table 1 Summary of key trials assessing sodium-glucose cotransporter 2 inhibitors in chronic kidney disease

Trial	SGLT2i	Population	Results (primary outcome)
CREDENCE[86]	Canagliflozin (100 mg)	Patients with T2D; eGFR 30-90 mL/minute and uACR > 300 to 5000 mg/g	↓Evolution to ESKD; ↓death from cardiovascular causes
DAPA-CKD[85]	Dapagliflozin (10 mg)	Regardless of T2D status; eGFR 25-75 mL/minute and uACR > 200 to 5000 mg/g	↓Sustained decline of eGFR of 50% or more; ↓evolution to ESKD
SCORED[88]	Sotagliflozin (200-400 mg)	Patients with T2D; eGFR 25-50 mL/minute (regardless of albuminuria); an additional CVD risk factor	↓Hospitalization and urgent visits due to heart failure
EMPA-KIDNEY[89]	Empagliflozin (10 mg)	Patients with and without T1D or T2D; eGFR 20-45 mL/minute (regardless of albuminuria); or eGFR 45-90 mL/minute (with uACR > 200 mg/g)	↓Progression of kidney disease

eGFR: Estimated glomerular filtration rate; uACR: Urinary albumin-to-creatinine ratio; T1D: Type 1 diabetes; T2D: Type 2 diabetes; CVD: Cardiovascular disease; SGLT2i: Sodium-glucose cotransporter 2 inhibitor; ESKD: End-stage kidney disease; CKD: Chronic kidney disease.

Table 2 Summary of key trials assessing glucagon-like peptide-1 versus placebo in diabetic kidney disease

Trial	GLP-1 RA	Population	Cardiovascular outcomes	Renal outcomes
ELIXA[149]	Lixisenatide (10-20 μg)	Patients with T2D and past MI or unstable angina; eGFR ≥ 30 mL/minute	No significant effect in MACE	↓uACR
EXSCEL[150]	Exenatide (2 mg)	Patients with T2D; with and without CKD or CVD; eGFR ≥ 30 mL/minute	No significant effect in MACE	No significant effects in renal outcomes
AMPLITUDE-O[151]	Efpeglenatide (4-6 mg)	Patients with T2D and CVD or eGFR 25-59.9 mL/minute with CVD risk factors	↓MACE	↓uACR
LEADER[153]	Liraglutide (1.8 mg)	Patients with T2D; with and without CKD	↓MACE	↓uACR
SUSTAIN 6[154]	Subcutaneous semaglutide (0.5-1 mg)	Patients with T2D; With and without CKD; eGFR ≥ 30 mL/minute	↓MACE	↓uACR
PIONEER 6[155]	Oral semaglutide (14 mg)	Patients with T2D; With and without CKD; eGFR ≥ 30 mL/minute	↓MACE	Not measured
REWIND[156]	Dulaglutide (1.5 mg)	Patients with T2D and CVD or CVD risk factors; eGFR ≥ 15 mL/minute	↓MACE	↓uACR
FLOW[148]	Subcutaneous semaglutide (1 mg)	Patients with T2D and CKD; eGFR of 25-75 mL/minute (uACR 300-5000 if eGFR ≥ 50 mL/minute)	↓MACE	↓uACR; ↓eGFR; ↓major kidney disease events

GLP-1 RA: Glucagon-like peptide-1 receptor agonists; eGFR: Estimated glomerular filtration rate; uACR: Urinary albumin-to-creatinine ratio; MI: Myocardial infarction; CVD: Cardiovascular Disease; T2D: Type 2 diabetes; MACE: Major adverse cardiovascular events; CKD: Chronic kidney disease.