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. 2022 Sep 29;7(12):2589–2607. doi: 10.1016/j.ekir.2022.09.018

Table 6.

Summary of select GLP-1RA cardiovascular outcome trials130, 131, 132, 133

Study LEADER (n = 9340) SUSTAIN-6 (n = 3297) AWARD-7 (n = 577) REWIND (n = 9901)
Agent Liraglutide Semaglutide Dulaglutide Dulaglutide
Median follow-up (yr) 3.8 2.1 52 wk 5.4
Prior CVD (%) 81 60 NA 31
Mean baseline A1C (%) 8.7 8.7 7.5–10.5 7.3
Kidney function at baseline (ml/min/1.73 m2) 21% eGFR 30–59
2% eGFR < 30		 25% eGFR 30–59
3% eGFR < 30		 26% eGFR 45–60
35% eGFR 30–44
31% eGFR < 30
46% UACR > 300 mg/g		 21.8% eGFR < 60
34.5% UACR > 30 mg/g
Primary outcomeb 3-point MACE
0.87 (0.78–0.97)		 3-point MACE
0.74 (0.58–0.95)		 HbA1C change from baseline to 26-weeks:
  • •

    Insulin glargine: −1.1%

  • •

    Dulaglutide 0.75 mg: −1.1%

  • •

    Dulaglutide 1.5 mg: −1.2%

  • •

    Noninferior (P ≤ 0.0001 for both dulaglutide doses vs. insulin glargine)

 3-point MACE
0.88 (0.79–0.99)
Secondary outcomes Lower incidence of composite
outcome (new onset
albuminuria, doubling
of sCr and CrCl
<45 ml/min, need for KRT, death due to renal causes)
1.5 events/100 patient/year in liraglutide
vs. 1.9 events
events/100 patient/year in placebo group (P = 0.003)		 Lower incidence of new or worsening
nephropathy:
3.8% in semaglutide vs. 6.1% in placebo
group (P = 0.005)
Lower rate of new onset macroalbuminuria:
2.5% in semaglutide vs. 4.9% in placebo		 eGFR decline (ml/min/1.73 m2):
• 3.3 insulin glargine
• 0.7 duaglutide 0.75 mga and 1.5 mga
• aP < 0.05 compared with glargine
eGFR decline (ml/min/1.73 m2) in UACR
> 300 mg/g group:
• 5.5 insulin glargine
• 0.7 dulaglutide 0.75 mga
• 0.5 dulaglutide 1.5 mga
• aP < 0.05 compared with glargine
UACR reduction:
• 13% insulin glargine
• 29% dulaglutide 1.5 mga
• aP < 0.05 compared with glargine		 Lower incidence of the composite
endpoint (new onset
macroalbuminuria,
≥30% decline in eGFR, or need for chronic
KRT); 17% in dulaglutide vs. 20% in placebo group (P < 0.001)
Worsening nephropathyb 0.78 (0.67–0.92) 0.64 (0.46–0.88) - 0.85 (0.77–0.93)

A1C, glycated hemoglobin; AWARD, X; CI, confidence interval; eGFR, glomerular filtration rate; GLP-1RA, glucagon-like peptide-1 receptor agonist; HR, hazard ratio; KRT, kidney replacement therapy; LEADER, A Long-term, Multi-centre, International, Randomised Double-blind, Placebo-controlled Trial to Determine Liraglutide Effects on Cardiovascular Events; MACE, major adverse cardiovascular events; REWIND, The Effect of Dulaglutide on Major Cardiovascular Events in Patients With Type 2 Diabetes: Researching Cardiovascular Events With a Weekly INcretin in Diabetes; SUSTAIN, A Long-term, Randomised, Double-blind, Placebo-controlled, Multinational, Multi-centre Trial to Evaluate Cardiovascular and Other Long-term Outcomes With Semaglutide in Subjects With Type 2 Diabetes; UACR, urine to albumin creatinine ratio.

a

Statistically significant.

b

Outcome data represented as HR and 95% CI.