Table 3.
Summaries of landmark trials with GLP-1 agonists.
| Trial | Year Published | Treatment (s) | Primary or Secondary | Kidney Outcome | Results |
|---|---|---|---|---|---|
| LEADER [39] | 2016 | Liraglutide vs. placebo | Secondary | Diabetic Nephropathy | HR 0.78 (95% CI 0.67–0.92) |
| SUSTAIN-6 [40] | 2016 | Semaglutide vs. placebo | Secondary | Macroalbuminuria, doubling of serum creatinine, Creatinine clearance ≤ 45 mL/min or KRT | HR 0.64 (95% CI 0.46–0.88) |
| AWARD-7 [41] | 2018 | Dulaglutide vs. insulin glargine | Secondary | eGFR and UACR | A decline in eGFR of the insulin arm but not in the higher-dose dulaglutide arm |
| REWIND [42] | 2019 | Dulaglutide vs. placebo | Secondary | 300 mg/g > UACR in lower baseline concentration, sustained 30% > eGFR decline, KRT | HR 0.85 (95% CI 0.77–0.93) |
| Kristensen et. al. meta-analysis [43] | 2019 | GLP-1′s | --- | New-onset macroalbuminuria, decline in eGFR, progression of kidney disease or death of kidney cause | HR 0.83 (95% CI 0.78–0.89) |
| AMPLITUDE-O [44] | 2021 | Efpeglenatide vs. placebo | Secondary | Incident microalbuminuria > 300 mg/g, increase in UACR of at least 30% from baseline, sustained eGFR decrease > 40% for > 30 days, KRT for 90 days or more, eGFR < 15 for 30 days or more | HR 0.68 (95% CI 0.57–0.79) |
| FLOW | To be completed in 2024 | Semaglutide vs. placebo | Primary | Persistent ≥ 50% reduction in eGFR, reaching ESKD, death from kidney disease or death from CV cause | Ongoing |
AMPLITUDE-O = cardiovascular and renal outcomes with efpeglenatide in type 2 diabetes; AWARD-7 = dulaglutide versus insulin glargine in patients with type 2 diabetes and moderate-to-severe chronic kidney disease; CI = confidence interval; CKRT = continuous kidney replacement therapy; CV = cardiovascular; FLOW = effect of semaglutide versus placebo on the progression of renal impairment in subjects with type 2 diabetes and chronic kidney disease; eGFR = estimated glomerular filtration rate; ESKD = end-stage kidney disease; HR = hazard ratio; KRT = kidney replacement therapy; LEADER = liraglutide effect and action in diabetes: evaluation of cardiovascular outcome results; REWIND = dulaglutide and cardiovascular outcomes in type 2 diabetes; SUSTAIN-6 = trial to evaluate cardiovascular and other long-term outcomes with semaglutide in subjects with type 2 diabetes; UACR = urine albumin to creatinine ratio.