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Glucagon-like peptide-1 receptor agonists and atrial fibrillation: a systematic review and meta-analysis of randomised controlled trials

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Abstract

Background

The pharmacological stimulation of GLP-1 receptors is associated with an increase in heart rate. A pooled analysis of patient-level data from phase III trials with albiglutide revealed a significant increase in the risk of atrial fibrillation. Aim of the present meta-analysis is to summarize all available evidence on the effects of individual GLP-1 receptor agonists (RA), and of the whole class, on the incidence of atrial fibrillation.

Methods

A Medline search for GLP-1 RA (exenatide, liraglutide, lixisenatide, albiglutide, dulaglutide, or semaglutide) was performed, collecting all randomized clinical trials with a duration ≥12 weeks, enrolling patients with type 2 diabetes and comparing a GLP-1 RA with placebo or any other non-GLP-1 RA drug.

Results

Of the 113 trials fulfilling the inclusion criteria, 19 did not report information on atrial fibrillation, whereas 63 reported zero events in all treatment groups. In the remaining trials (enrolling 17,966 and 15,305 patients in GLP-1 RA and comparator arms, respectively, 55.3% women, with a mean age of 57.0 ± 3.8 years), treatment with GLP-1 RA was not associated with a significant increase in the incidence of atrial fibrillation [Mantel–Haenszel OR (95% CI) 0.87 (0.71–1.05), p = 0.15].

Conclusions

In conclusion, available data suggest that GLP-1 RA is not associated with atrial fibrillation, with the only possible exception of albiglutide. Newly onset atrial fibrillation deserves to be investigated as an event of special interest in future trials with GLP-1 RA.

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Acknowledgements

This research was performed independently of any funding as part of the institutional activity of the investigators.

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Authors and Affiliations

  1. Diabetology, Azienda Ospedaliero Universitaria Careggi, University of Florence, Via delle Oblate 4, 50141, Florence, Italy

    M. Monami, B. Nreu, S. Giannini & E. Mannucci

  2. Diabetology Unit, Ospedale San Donato Arezzo, Arezzo, Italy

    A. Scatena

  3. Department of Medical and Surgical Sciences, University Magna Graecia of Catanzaro, Catanzaro, Italy

    F. Andreozzi & G. Sesti

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  1. M. Monami
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Correspondence to M. Monami.

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Conflict of interest

Matteo Monami has received speaking fees from Bristol Myers Squibb, Eli-Lilly, Merck, Novo Nordisk, Merck, and Takeda, and research grants from Bristol Myers Squibb. Nreu Besmir, Alessia Scatena, Stefano Giannini, Francesco Andreozzi have no conflicts of interest. Giorgio Sesti has received consultancy fees from Servier, Intarcia, Novo Nordisk, Janssen, Boehringer Ingelheim, Eli Lilly, Astra Zeneca, MSD Italy, Sanofi, Pfizer, and Abbott, and speaking fees from Novo Nordisk, MSD Italy, Boehringer Ingelheim, Eli Lilly, Janssen, Astra Zeneca, Theras Lifetech and Takeda. Edoardo Mannucci has received consultancy fees from Merck and Novartis, speaking fees from Astra Zeneca, Bristol Myers Squibb, Merck, and Novartis, and research grants from Merck, Novartis, and Takeda.

Ethical approval

This article does not contain any studies with human participants or animals performed by any of the authors.

Informed consent

For this type of study informed consent was not necessary.

Author contributions

MM was involved in each of the following points: 1. design, 2. data collection, 3. analysis, 4. writing manuscript. BN, AS, and SG were involved in each of the following points: 1. data collection, 2. manuscript revision. GS was involved in each of the following points: 1. design, 2. reviewing manuscript. EM was involved in each of the following points: 1. design, 2. data collection, 3. analysis, 4. writing manuscript. All the authors approved the final version of this manuscript.

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Monami, M., Nreu, B., Scatena, A. et al. Glucagon-like peptide-1 receptor agonists and atrial fibrillation: a systematic review and meta-analysis of randomised controlled trials. J Endocrinol Invest 40, 1251–1258 (2017). https://doi.org/10.1007/s40618-017-0698-7

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  • DOI: https://doi.org/10.1007/s40618-017-0698-7

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