Cardiorenal protective effects of glucagon-like peptide-1 receptor agonists in chronic kidney disease: a systematic review and meta-analysis.
GLP-1 receptor agonists may reduce major kidney and cardiovascular events in CKD patients with type 2 diabetes, but they are associated with significant gastrointestinal side effects.
Where it sits
this study against the rest of the dulaglutide corpusSummary and findings
This systematic review and meta-analysis evaluated the cardiorenal outcomes and adverse effects of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) in patients with chronic kidney disease (CKD). The analysis included nine trials with a total of 21,717 patients, primarily those with type 2 diabetes mellitus (T2DM). Findings indicated a reduction in major adverse kidney events and all-cause mortality, alongside increased gastrointestinal events.
Abstract
Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are widely used in patients with chronic kidney disease (CKD), but existing evidence regarding their efficacy and safety remains inconsistent. To evaluate the cardiorenal outcomes and adverse effects of GLP-1 RAs in this population, we conducted a systematic review and meta-analysis of randomized controlled trials from PubMed, Embase, Cochrane Central Register of Controlled Trials, and Web of Science up to December 2024. Nine trials involving 21,717 patients, the vast majority of whom had T2DM, were included. GLP-1RAs treatment for CKD was associated with decreasing the incidence of major adverse kidney events (MAKE; RR, 0.84; 95% CI, 0.76-0.94) and major adverse cardiac and cerebrovascular events (MACE; RR, 0.84; 95% CI, 0.72-0.97), reducing all-cause mortality (RR, 0.83; 95% CI, 0.76-0.90) and albuminuria level (SMD, -1.22; 95% CI, -1.53 - 0.90). Gastrointestinal events associated with GLP-1 RA treatments including nausea (RR, 4.14; 95% CI, 2.70-6.33), vomiting (RR, 3.05; 95% CI, 1.88-4.97), diarrhea (RR, 2.65; 95% CI, 1.76-3.98), and dyspepsia (RR, 3.79; 95% CI, 1.02-14.12) have garnered significant attention. In conclusion, administration of GLP-1RAs treatment demonstrates excellent cardiorenal protective effects in CKD, primarily in patients with co-existing T2DM, though with notable gastrointestinal concerns.
Background
This paper addresses the efficacy and safety of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) in patients with chronic kidney disease (CKD). Prior studies have shown inconsistent results regarding the cardiorenal benefits of GLP-1 RAs, particularly in populations with co-existing conditions such as type 2 diabetes mellitus (T2DM). Understanding these effects is crucial as CKD management often requires careful consideration of both renal and cardiovascular outcomes.
Methods
The study conducted a systematic review and meta-analysis of randomized controlled trials from databases including PubMed, Embase, Cochrane Central Register of Controlled Trials, and Web of Science, up to December 2024. A total of nine trials involving 21,717 patients were included, primarily those diagnosed with T2DM. The analysis focused on primary outcomes such as major adverse kidney events (MAKE), major adverse cardiac and cerebrovascular events (MACE), and all-cause mortality, alongside secondary outcomes like albuminuria levels.
Results
The primary endpoint for all-cause mortality showed a risk ratio (RR) of 0.83 with a 95% confidence interval (CI) of 0.76-0.90. Additionally, the incidence of major adverse kidney events (MAKE) was reduced with an RR of 0.84 (95% CI, 0.76-0.94), and major adverse cardiac and cerebrovascular events (MACE) also showed a reduction with an RR of 0.84 (95% CI, 0.72-0.97). The standardized mean difference (SMD) for albuminuria levels was reported as -1.22 (95% CI, -1.53 to -0.90).
Interpretation
The findings suggest that GLP-1 RAs may provide some cardiorenal protective effects in CKD patients, particularly those with T2DM. However, while the statistical significance of the results is noted, the clinical significance may be limited by the presence of gastrointestinal side effects and the predominance of T2DM in the study population. Furthermore, the potential for confounding factors, such as the short duration of follow-up and the reliance on surrogate endpoints, should be considered when interpreting these results.
Key findings
- RR for major adverse kidney events (MAKE) was 0.84; 95% CI, 0.76-0.94.
- RR for major adverse cardiac and cerebrovascular events (MACE) was 0.84; 95% CI, 0.72-0.97.
- RR for all-cause mortality was 0.83; 95% CI, 0.76-0.90.
- SMD for albuminuria level was -1.22; 95% CI, -1.53 to -0.90.
- RR for nausea was 4.14; 95% CI, 2.70-6.33.
- RR for vomiting was 3.05; 95% CI, 1.88-4.97.
Limitations
- Majority of trials involved patients with type 2 diabetes mellitus.
- Gastrointestinal side effects raise concerns about tolerability.
- Not all outcomes may be generalizable to non-diabetic CKD patients.
- Short follow-up duration may not capture long-term effects.
- Potential for confounding factors not fully addressed.