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Meta-Analysis
. 2021 Sep 15;20(1):189.
doi: 10.1186/s12933-021-01366-8.

GLP-1 receptor agonists and cardiorenal outcomes in type 2 diabetes: an updated meta-analysis of eight CVOTs

Dario Giugliano #  1   2 , Lorenzo Scappaticcio #  3   4 , Miriam Longo #  3   4 , Paola Caruso  3   4 , Maria Ida Maiorino  5 , Giuseppe Bellastella  3 , Antonio Ceriello  6 , Paolo Chiodini  7 , Katherine Esposito  4   5
Affiliations
Meta-Analysis

GLP-1 receptor agonists and cardiorenal outcomes in type 2 diabetes: an updated meta-analysis of eight CVOTs

Dario Giugliano et al. Cardiovasc Diabetol. .

Abstract

Background: A meta-analysis is presented of cardiovascular outcome trials (CVOTs) comparing glucagon-like peptide-1 receptor agonists (GLP-1RA) versus placebo on cardiorenal outcomes in patients with type 2 diabetes mellitus (T2DM).

Methods: We did an electronic search up to June 30, 2021, for eligible trials. We did a meta-analysis of available trial data using a random-effects model to calculate overall hazard ratios (HRs) and 95% CI (confidence intervals). We included data from 8 CVOTs and 60,080 patients (72.4% with established cardiovascular disease).

Results: GLP-1RA reduced major cardiovascular events (MACE) by 14% (HR = 0.86, 95% CI 0.79-0.94, P = 0.006) with a non-significant heterogeneity between subgroups of patients with and without cardiovascular disease (P = 0.127). GLP-1RA also reduced the risk of cardiovascular death by 13% (P = 0.016), nonfatal stroke by 16% (P = 0.007), hospitalization for heart failure by 10% (P = 0.023), all-cause mortality by 12% (P = 0.012), and the broad composite kidney outcome by 17% (P = 0.012), which was driven by a reduction in macroalbuminuria only (HR = 0.74, 0.67-0.82, P < 0.001).

Conclusions: GLP-1RA have moderate benefits on MACE, and also reduce hospitalization for heart failure and all-cause mortality; they also have robust benefits on reducing the incidence of macroalbuminuria.

Keywords: Albiglutide; Cardiorenal outcomes; Cardiovascular outcome trials; Dulaglutide; Efpeglenatide; Exenatide; GLP-1RA; Liraglutide; Lixisenatide; Oral semaglutide; Semaglutide; Type 2 diabetes.

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Conflict of interest statement

D. G. received a consultancy fee from Eli Lilly and has held lectures for Eli Lilly, Boehringer Ingelheim, Novo Nordisk, Novartis, Mundipharma, Sanofi. M. I. M. has held lectures for Astrazeneca, Sanofi, NovoNordisk, and MSD. K. E. received a consultancy fee from Eli Lilly and has held lectures for Eli Lilly, Sanofi, and Novo Nordisk. A.C. has been an advisory board member for Abbott, Astra Zeneca, Boehringer Ingelheim, DOC Generici, Eli Lilly, Janssen, Mundipharma, Novo Nordisk and OM Pharma; has given lectures for Astra Zeneca, Berlin Chemie, Boehringer Ingelheim, Eli Lilly, Mundipharma, Novo Nordisk and Roche Diagnostics; and has received research grants from Astra Zeneca, Eli Lilly, Mitsubishi and Novartis. No other potential conflicts of interest relevant to this article were reported.

Figures

Fig. 1
Fig. 1
Process of studies’ selection
Fig. 2
Fig. 2
Cochrane risk of bias (graph) for the 8 trials
Fig. 3
Fig. 3
Forest plots of meta-analysis of the eight CVOTs with GLP-1RA on MACE. The results are expressed as HR (hazard ratio)
Fig. 4
Fig. 4
Forest plots of meta-analysis of the six CVOTs with GLP-1RA on MACE, in patients with history of CV disease (top) or in patients without such a history (bottom)
Fig. 5
Fig. 5
Forest plots of meta-analysis of the eight CVOTs with GLP-1RA on CV mortality
Fig. 6
Fig. 6
Forest plots of meta-analysis of the eight CVOTs with GLP-1RA on nonfatal stroke
Fig. 7
Fig. 7
Forest plots of meta-analysis of the eight CVOTs with GLP-1RA on nonfatal myocardial infarction
Fig. 8
Fig. 8
Forest plots of meta-analysis of the eight CVOTs with GLP-1RA on hospitalization for heart failure
Fig. 9
Fig. 9
Forest plots of meta-analysis of the eight CVOTs with GLP-1RA on composite renal endpoint
Fig. 10
Fig. 10
Forest plots of meta-analysis of the eight CVOTs with GLP-1RA on incidence of new macroalbuminuria
See this image and copyright information in PMC

References

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