Selected clinical trials of GLP-1 RA, liraglutide, semaglutide, and dulaglutide
| GLP-1 RA | Trial | Intervention | N | Mean baseline eGFR (mL/min/1.73 m2) | Median follow-up (years) | Primary composite outcome (HR (95% CI)) | Kidney outcome (HR (95% CI)) |
| Liraglutide | LEADER | Liraglutide 1.8 mg subcutaneous once per day or placebo | 9340 | 80.4 | 3.8 | Death from cardiovascular causes, non-fatal (including silent) myocardial infarction, or non-fatal stroke (0.87 (0.78 to 0.97)) | New-onset albuminuria, doubling of serum creatinine and eGFR of <45 mL/min/1.73 m2, need for continuous renal replacement therapy, or death due to renal disease (0.78 (0.67 to 0.92)) |
| Semaglutide | SUSTAIN-6 | Semaglutide 0.5 mg subcutaneous once weekly, semaglutide 1.0 mg subcutaneous once weekly, or placebo | 3297 | Not reported. 28% eGFR of <60 mL/min/1.73 m2 | 2.1 | Death from cardiovascular causes, non-fatal myocardial infarction (including silent), or non-fatal stroke (0.74 (0.58 to 0.95)) | New or worsening nephropathy (0.64 (0.46 to 0.88)) |
| PIONEER-6 | Semaglutide 14 mg oral once per day or placebo | 3183 | 74 | 1.3 | Death from cardiovascular causes (including undetermined causes of death), non-fatal myocardial infarction, or non-fatal stroke (0.79 (0.57 to 1.11)) | None. There was no significant difference in the change in eGFR from baseline or in the rate of renal death. | |
| Dulaglutide | REWIND | Dulaglutide 1.5 mg subcutaneous once a week or placebo | 9901 | 77 | 5.4 | Non-fatal myocardial infarction, non-fatal stroke, or death from cardiovascular causes (including unknown causes) (0.88 (0.79 to 0.99)) | UACR of >33.9 mg/mmol in those with a lower baseline concentration, sustained 30% or greater decline in eGFR based on two consecutive eGFR concentrations, or chronic renal replacement therapy (0.85 (0.77 to 0.93)) |
| AWARD-7 | Dulaglutide 1.5 mg subcutaneous once weekly, dulaglutide 0.75 mg subcutaneous once weekly, or insulin glargine titrated daily | 577 | 38.3 | Total 52 weeks | At 26 weeks, change in HbA1c with dulaglutide 0.75 mg (LSM difference −1.1% (SE 0.1) and dulaglutide 1.5 mg (−1.2% (0.1)) was not statistically different from insulin glargine (−1.1% (0.1)). | At 52 weeks, eGFR with dulaglutide of 0.75 mg (mean 33.8 mL/min/1.73 m2 (SE 0.7), p=0.009) and dulaglutide of 1.5 mg (34.0 mL/min/1.73 m2 (0.7), p=0.005) were statistically different from insulin glargine (31.3 mL/min/1.73 m2 (0.7)); UACR reduction with dulaglutide of 0.75 mg and dulaglutide 1.5 mg were not significantly different from insulin glargine. |
AWARD-7, Dulaglutide vs Insulin Glargine in Patients with Type 2 Diabetes and Moderate-to-Severe CKD; eGFR, estimated glomerular filtration rate; GLP-1 RA, glucagon-like peptide-1 receptor agonist; HbA1c, glycated hemoglobin; LEADER, Liraglutide and Cardiovascular Outcomes in Type 2 Diabetes; LSM, least squares mean; PIONEER-6, Oral Semaglutide and Cardiovascular Outcomes in Patients with Type 2 Diabetes; REWIND, Dulaglutide and Cardiovascular Outcomes in Type 2 Diabetes; SUSTAIN-6, Semaglutide and Cardiovascular Outcomes in Patients with Type 2 Diabetes; UACR, urine albumin-to-creatinine ratio.