M Monami1, B Nreu2, A Scatena3, S Giannini2, F Andreozzi4, G Sesti4, E Mannucci2. 1. Diabetology, Azienda Ospedaliero Universitaria Careggi, University of Florence, Via delle Oblate 4, 50141, Florence, Italy. matteo.monami@unifi.it. 2. Diabetology, Azienda Ospedaliero Universitaria Careggi, University of Florence, Via delle Oblate 4, 50141, Florence, Italy. 3. Diabetology Unit, Ospedale San Donato Arezzo, Arezzo, Italy. 4. Department of Medical and Surgical Sciences, University Magna Graecia of Catanzaro, Catanzaro, Italy.
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.
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.
Authors: Steven P Marso; Stephen C Bain; Agostino Consoli; Freddy G Eliaschewitz; Esteban Jódar; Lawrence A Leiter; Ildiko Lingvay; Julio Rosenstock; Jochen Seufert; Mark L Warren; Vincent Woo; Oluf Hansen; Anders G Holst; Jonas Pettersson; Tina Vilsbøll Journal: N Engl J Med Date: 2016-09-15 Impact factor: 91.245
Authors: Matteo Monami; Stefania Zannoni; Laura Pala; Antonio Silverii; Francesco Andreozzi; Giorgio Sesti; Edoardo Mannucci Journal: Int J Cardiol Date: 2017-05-05 Impact factor: 4.164
Authors: Steven P Marso; Jason B Lindsey; Joshua M Stolker; John A House; Gabriela Martinez Ravn; Kevin F Kennedy; Troels M Jensen; John B Buse Journal: Diab Vasc Dis Res Date: 2011-06-08 Impact factor: 3.291
Authors: Mark M Smits; Marcel H A Muskiet; Lennart Tonneijck; Trynke Hoekstra; Mark H H Kramer; Michaela Diamant; Daniël H van Raalte Journal: Br J Clin Pharmacol Date: 2016-01-25 Impact factor: 4.335
Authors: Steven P Marso; Gilbert H Daniels; Kirstine Brown-Frandsen; Peter Kristensen; Johannes F E Mann; Michael A Nauck; Steven E Nissen; Stuart Pocock; Neil R Poulter; Lasse S Ravn; William M Steinberg; Mette Stockner; Bernard Zinman; Richard M Bergenstal; John B Buse Journal: N Engl J Med Date: 2016-06-13 Impact factor: 176.079
Authors: Martin Aguilar; Robert A Rose; Abhijit Takawale; Stanley Nattel; Svetlana Reilly Journal: Cardiovasc Res Date: 2021-06-16 Impact factor: 10.787