Table 1.

Secondary kidney outcomes in clinical trials of glucagon like peptide-1 receptor agonists in patients with type 2 diabetes

Name of the Study	Agent	Intervention	Study Population	Kidney Outcomes	Results
Clinical trial for glycemic control in moderate-to-severe chronic kidney disease
AWARD-7* (n = 576)	Dulaglutide	Dulaglutide 0.75 and 1.5 mg vs. insulin glargine	Type 2 diabetes7.5% ≥ HbA1c ≤ 10.5%15 ≥ eGFR ≤ 6 0 ml·min−1·1.73 m−2Baseline means ± SD eGFR: 35 ± 0.6 ml·min−1·1.73 m−2Baseline median (interquartile range): UACR (mg/g): 209 (39–965)	eGFR and UACR change from baseline	eGFR in dulaglutide 1.5 mg (−1.1 ml·min−1·1.73 m−2, P < 0.05), and 0.75 mg (−1.5 ml·min−1·1.73 m−2 m2, P < 0.05) groups vs. eGFR in insulin glargine group (−2.9 ml·min−1·1.73 m−2 V, P < 0.0001)
					In those with UACR >300 mg/g, eGFR decline was less with dulaglutide (1.5 mg: −0.5 ml·min−1·1.73 m−2, P < 0.05 vs. insulin; 0.75 mg: −0.7 ml·min−1·1.73 m−2, P < 0.05 vs. insulin; insulin: −5.5 ml·min−1·1.73 m−2)
					UACR reduction in dulaglutide 1.5 mg −29% (−34, −11.5), and −12.3% (−29,8.5) in 0.75 mg vs. insulin −13% (27.1, −39); P = 0.020 and P = 0.363, respectively)
Clinical trials for cardiovascular safety
LEADER† (n = 9,340)	Liraglutide	1.8 mg (or the maximum tolerated dose) vs. placebo	Type 2 diabetes	New-onset albuminuria, doubling of sCr and CrCl <45 ml·min−1·1.73 m−2; RRT; death due to kidney disease	1.9 events/100 patient-year in placebo group vs. 1.5 events/100 patient-year in liraglutide group (P = 0.003)
			HbA1c >7%
			Prevalent CVD
			Baseline eGFR: n/N (%):
			eGFR >90 ml·min−1·1.73 m−2:
			placebo [1,655/4,672 (35.4)]; liraglutide [1,620/4,668 (34.7)]
			eGFR 60 ≤ 90 ml·min−1·1.73 m−2: placebo [1,975/4,672 (41.4)]; liraglutide [1,932/4,668 (42.3)]
			eGFR 30 ≤ 60 ml·min−1·1.73 m−2: placebo [935/4,672 (20.0)]; liraglutide [999/4,668 (21.4)]
			eGFR <30 ml·min−1·1.73 m−2:
			placebo [107/4,672 (2.3)];
			liraglutide [117/4,668 (2.5)]
			Microalbuminuria or proteinuria at baseline: n/N (%):
			placebo: 558/4,672 (11.9%);
			liraglutide: 501/4,668 (10.7%)
ELIXA‡ (n = 6,068)	Lixisenatide	10–20 μg of lixisenatide vs. placebo	Type 2 diabetes5.5% ≥ HbA1c ≤ 11%	Proportional change in UACR from baseline to 108 wk	24 vs. 34% reduction in UACR in placebo group vs. lixisenatide group (P = 0.004)
			Recent acute coronary syndrome
			Baseline means ± SD eGFR:
			placebo: 75.2 ± 21.4 ml·min−1·1.73 m−2; lixisenatide: 76.7 ± 21.3 ml·min−1·1.73 m−2
			Baseline median (interquartile range) UACR (mg/g):
			placebo: 10.4 (5.9–32.6); lixisenatide: 10.0 (6.0 −28.0)
SUSTAIN-6¶ (n = 3,297)	Semaglutide	0.5 mg vs. 1.0 mg of semaglutide vs. placebo	Type 2 diabetesHbA1c >7%	New or worsening nephropathy (persistent UACR >300 mg/g; doubling of sCr or eGFR <45 ml·min−1·1.73 m−2; RRT)	6.1% with composite outcome in placebo group vs. 3.8% in semaglutide group (P = 0.005)
			Age >50 yr with established CVD or CKD stages 3–5
			Age >60 yr with CVD risk factors
			Baseline eGFR n/N (%):
			eGFR >90: 990/3,297 (30)
			eGFR 60 ≤ 90: 1,368/3,297 (41.5)
			eGFR 30 ≤ 60: 832/3,297 (25.2)
			eGFR 15 ≤ 30: 95/3,297 (2.9)
			eGFR <15: 12/3,297 (0.4)

UAC, urine albumin-to-creatinine ratio (with albumin measured in mg/g); CKD, chronic kidney disease, CVD, cardiovascular disease; sCr, serum creatinine; CrCl, creatinine clearance; RRT, renal replacement therapy; HbA1c, hemoglobin A1c; eGFR, estimated glomerular filtration rate in ml·min⁻¹·1.73 m⁻².

^*A Randomized, Open-Label, Parallel-Arm Study Comparing the Effect of Once-weekly Dulaglutide With Insulin Glargine on Glycemic Control in Patients With Type 2 Diabetes and Moderate or Severe Chronic Kidney Disease (AWARD-7) (36).

^†Liraglutide Effect and Action in Diabetes: Evaluation of Cardiovascular Outcome Results (LEADER) (21, 22).

^‡Lixisenatide in Patients with Type 2 Diabetes and Acute Coronary Syndrome (ELIXA) (26).

^¶Semaglutide and Cardiovascular Outcomes in Patients with Type 2 Diabetes (SUSTAIN-6) (23).