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Updated: Oct 20, 2025
Assessment of Vascular Function in Patients With Chronic Kidney Disease
Published on: June 16, 2014
Systematic Review of Cardiovascular Outcome Trials Using New Antidiabetic Agents in CKD Stratified by Estimated GFR
Adam Arshad1, Nadia Sarween2, Adnan Sharif2,3
1University College Hospitals, London, UK.
Insights
New antidiabetic agents show cardiovascular benefits, but evidence in chronic kidney disease (CKD) patients is limited. Sodium-glucose cotransporter-2 (SGLT-2) inhibitors are effective for major adverse cardiovascular events (MACE) in CKD patients with reduced eGFR.
Area of Science:
- Nephrology
- Cardiology
- Endocrinology
Background:
- Cardiovascular benefits of novel antidiabetic agents may not apply to patients with chronic kidney disease (CKD).
- Systematic review and meta-analysis of cardiovascular outcome trials (CVOTs) were performed, stratifying by kidney function.
Purpose of the Study:
- To evaluate the cardiovascular outcomes of new antidiabetic agents in patients with varying degrees of kidney function.
- To determine if the cardiovascular benefits of these agents extend to patients with chronic kidney disease.
Main Methods:
- Searched MEDLINE and Cochrane Central Register up to November 16, 2020.
- Extracted major adverse cardiovascular event (MACE) data from 16 trials (GLP-1, DPP-4, SGLT-2 inhibitors) involving 150,816 participants.
- Performed meta-analysis stratified by estimated glomerular filtration rate (eGFR) and albuminuria.
Main Results:
- GLP-1 analogues showed a trend towards MACE reduction in CKD patients (eGFR <60 ml/min per 1.73 m²), but lacked statistical significance (RR 0.90; P=0.14).
- DPP-4 inhibitors showed no significant effect on MACE in any kidney function group (RR 0.99; P=0.86).
- SGLT-2 inhibitors demonstrated significant MACE reduction in CKD patients with reduced eGFR (RR 0.85; P=0.005), but not in those with preserved eGFR (RR 1.01; P=0.87).
Conclusions:
- Sodium-glucose cotransporter-2 (SGLT-2) inhibitors provide clear evidence for major adverse cardiovascular event (MACE) prevention in diabetes patients with reduced estimated glomerular filtration rate (eGFR <60 ml/min per 1.73 m²).
- Glucagon-like peptide-1 (GLP-1) analogue effect sizes suggest potential efficacy in CKD patients, but current trials may lack sufficient statistical power to confirm this benefit.
Introduction:
Cardiovascular benefits observed with new antidiabetic agents may not extend to chronic kidney disease (CKD) patients. This study performed a systematic review and meta-analysis of cardiovascular outcome trials (CVOTs) using new antidiabetic agents stratified by kidney function.
Methods:
MEDLINE (via PubMed) and the Cochrane Central Register of Controlled Trials were searched for eligible studies up to November 16, 2020. Data were stratified by the trial entry estimated glomerular filtration rate (eGFR) and albuminuria. Primary major cardiovascular event (MACE) outcomes were extracted, and a meta-analysis with a random effects model was performed to estimate overall risk ratios (RRs).
Results:
Our search identified 16 studies for inclusion (glucagon-like peptide-1 [GLP-1] analogues, n = 6; dipeptidyl-peptidase 4 [DPP-4] inhibitors, n = 4; and sodium-glucose cotransporter-2 [SGLT-2] inhibitors, n = 6) with a combined total of 150,816 participants (28.2% with eGFR <60 ml/min per 1.73 m2, n = 42,534). The RR for MACE with GLP-1 analogues with an eGFR ≥60 ml/min per 1.73 m2 was 0.87 (95% confidence interval [CI], 0.77-0.98; P = 0.02) and 0.90 (95% CI, 0.78-1.04; P = 0.14) with an eGFR <60 ml/min per 1.73 m2. The RR for MACE with DPP-4 inhibitors with eGFR ≥60 ml/min per 1.73 m2 was 0.99 (95% CI, 0.92-1.07; P = 0.86) and 0.99 (95% CI, 0.91-1.08; P = 0.86) with an eGFR <60 ml/min per 1.73 m2. The RR for MACE with SGLT-2 inhibitors with an eGFR ≥60 ml/min per 1.73 m2 was 1.01 (95% CI, 0.92-1.10; P = 0.87) and 0.85 (95% CI, 0.75-0.95; P = 0.005) with an eGFR <60 ml/min per 1.73 m2. Most analyses had significant heterogeneity. Sufficient albuminuria data were unavailable to analyze empirically.
Conclusion:
Clear evidence for MACE prevention in diabetes patients with an eGFR <60 ml/min per 1.73 m2 currently exists for SGLT-2 inhibitors only. However, similar GLP-1 analogue effect sizes suggest a lack of sufficient power rather than a lack of effect.
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