Highlights
- •Disparities were found in the cardiorenal outcomes among different GLP-1RAs.
- •GLP-1RAs with high concentration was associated with less cardiorenal events.
- •Long acting GLP-1RAs was associated more improved cardiovascular outcomes.
- •The molecular weight of GLP-1RAs did not influence the cardiorenal outcomes.
Abstract
Importance
Disparities were found in the cardiovascular and renal outcomes among different glucagon-like
peptide 1 receptor agonist (GLP-1RA) subtypes. However, whether the characteristics
of GLP-1RA itself are associated with these disparities remains unclear.
Objective
To assess the association between the steady-state concentration, duration of action,
or molecular weight of GLP-1RA and the risks of cardiovascular and renal outcomes
in patients with type 2 diabetes (T2D).
Data Sources
PubMed, MEDLINE, EMBASE, Cochrane and Clinicaltrial.gov from inception to April 2022.
Study Selection
Randomized controlled trials (RCTs) investigating GLP-1RAs in patients with T2D were
included.
Data Extraction And Synthesis
Literature screening and data extraction were performed independently by 2 researchers.
The outcomes were computed as odds ratio (OR) and its 95% confidence interval (CI).
Subgroup analyses were conducted according to steady-state concentration, duration
of action and molecular weight of GLP-1RAs.
Main Outcomes and Measures
Primary outcomes were major adverse cardiovascular events (MACE), composite renal
outcome and all-cause mortality.
Results
In all, 61 RCTs were included. When compared with non-GLP-1RA agents, GLP-1RAs with
high steady-state concentration were associated with greater risk reduction in MACE
(p for subgroup difference = 0.01) and the composite renal outcome (p for subgroup
difference = 0.008) in patients with T2D. Greater risk reductions in MACE between
GLP-1RA users versus non-GLP-RA users were observed in long acting stratum when compared
with short acting stratum (p for subgroup difference = 0.04) in patients with T2D.
The molecular weight of GLP-1RAs was not associated with the risk of cardiovascular
and renal outcomes.
Conclusions and Relevance
GLP-1RAs with high steady-state concentrations might be associated with greater risk
reductions in cardiovascular and renal outcomes in patients with T2D. Long acting
GLP-1RAs might outperform short acting ones in reducing the risk of cardiovascular
outcomes. These findings provided new insights for guiding the clinical applications
of GLP-1RAs in patients with T2D.
Keywords
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Article info
Publication history
Published online: January 09, 2023
Accepted:
January 5,
2023
Received in revised form:
January 2,
2023
Received:
October 26,
2022
Publication stage
In Press Corrected ProofIdentification
Copyright
© 2023 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.
