Impact of GLP-1 receptor agonist-based therapies on cardiovascular and renal outcomes in diabetic and non-diabetic patients with CKD

Abstract

Background: The effect of glucagon-like peptide-1 (GLP-1) receptor agonists-based therapies on cardiovascular and renal outcomes has not been systematically reviewed across baseline kidney function groups. We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) with GLP-1 Receptor Agonists (RAs) in patients with and without chronic kidney disease (CKD).

Methods: We performed a PubMed/Medline search of randomized, placebo-controlled, event-driven outcome trials of GLP-1 RAs versus placebo in patients with and without diabetes from inception to January 2025. CKD was defined as an estimated glomerular filtration rate (eGFR) < 60 ml/min/1.73m2. The primary outcome was major adverse cardiovascular events (MACE). Secondary outcomes included hospitalization for heart failure, CKD progression, cardiovascular and all-cause mortality. The relative risk (RR) was estimated using a random-effects model.

Results: Nine RCTs were included with a total of 75,088 patients, including 17,568 with eGFR < 60 ml/min/1.73m2. Use of an GLP-1 RA in patients with CKD was associated with a lower incidence of MACE (RR 0.84; 95% CI 0.74-0.95; P 0.006) and of CKD progression (RR 0.85, 95% CI 0.77-0.94; P 0.002), compared with placebo. There was no differential treatment effect of GLP-1 RA on these endpoints by CKD status at baseline.

Conclusions: GLP-1 RAs offer substantial cardiovascular and renal protection in patients with CKD. These findings support their use in CKD patients and confirms that these therapies may be continued as kidney function declines.

Fig. 1

Incidence of MACE. Incidence of major adverse cardiovascular events (MACE) with GLP-1 agonists compared with placebo in patients with and without chronic kidney disease (CKD). Results are stratified by CKD status. Data are presented as risk ratios (RR) with 95% confidence intervals (95%-CI). A similar incidence of MACE is identified with GLP-1 agonists compared with placebo in patients with and without CKD. A random effects model is used. Definition of MACE is detailed in Table 1

Fig. 2

Incidence of composite renal outcome with GLP-1 agonists compared with placebo in patients with and without chronic kidney disease (CKD). Results are stratified by CKD status. Data are presented as risk ratios (RR) with 95% confidence intervals (95%-CI). A similar incidence of composite renal outcome is identified with GLP-1 agonists compared with placebo in patients with and without CKD. A random effects model is used. Definition of the composite renal outcome is detailed in Table 1

Fig. 3

Incidence of cardiovascular death with GLP-1 agonists compared with placebo in patients with and without chronic kidney disease (CKD). Results are stratified by CKD status. Data are presented as risk ratios (RR) with 95% confidence intervals (95%-CI). A similar incidence of cardiovascular death is identified with GLP-1 agonists compared with placebo in patients with and without CKD. A random effects model is used

Fig. 4

Incidence of heart failure with GLP-1 agonists compared with placebo in patients with and without chronic kidney disease (CKD). Results are stratified by CKD status. Data are presented as risk ratios (RR) with 95% confidence intervals (95%-CI). A similar incidence of heart failure is identified with GLP-1 agonists compared with placebo in patients with and without CKD. A random effects model is used

Fig. 5

Incidence of mortality with GLP-1 agonists compared with placebo in patients with and without chronic kidney disease (CKD). Results are stratified by CKD status. Data are presented as risk ratios (RR) with 95% confidence intervals (95%-CI). A similar incidence of mortality is identified with GLP-1 agonists compared with placebo in patients with and without CKD. A random effects model is used