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Glucagon-like peptide-1 receptor agonists and the risk of atrial fibrillation in adults with diabetes: a real-world study

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Abstract

Background

Glucagon-like peptide-1 receptor agonists (GLP-1RA) have cardiovascular benefits in type 2 diabetes, but none of the cardiovascular trials studied atrial fibrillation/atrial flutter (AF) as a primary endpoint. Data from post-marketing surveillance studies remains sparse.

Objective

To examine the real-world risk of AF comparing GLP-1RA with other non-insulin glucose-lowering agents.

Design

Cohort study using de-identified electronic health record data from the Optum Labs Data Warehouse.

Participants

Adult patients with diabetes who were newly prescribed add-on non-insulin glucose-lowering agents and were on metformin between 2005-2020.

Exposures

New users of GLP-1RA were separately compared with new users of dipeptidyl peptidase-4 inhibitors (DPP4i) and sodium-glucose cotransporter 2 inhibitors (SGLT2i), using 1:1 propensity score matching to adjust for differences in patient characteristics.

Main Measures

The primary outcome was incident AF, defined and captured by diagnosis code for AF. Incidence rate difference (IRD) and hazard ratio (HR) were estimated in the matched cohorts.

Key Results

In the matched cohort of 14,566 pairs of GLP-1RA and DPP4i followed for a median of 3.8 years, GLP-1RA use was associated with a lower risk of AF (IRD, -1.0; 95% CI, -1.8 to -0.2 per 1000 person-years; HR, 0.82; 95% CI, 0.70 to 0.96). In the matched cohort of 9,424 pairs of patients on GLP-1RA and SGLT2i with a median follow-up of 2.9 years, there was no difference in the risk for AF (IRD, 0.4; 95% CI -0.7 to 1.5 per 1000 person-years; HR, 1.12; 95% CI, 0.89 to 1.42).

Conclusions

In this real-word study, GLP-1RA was associated with a lower risk of AF compared with DPP4i, but no difference compared with SGLT2i, suggesting that cardiovascular benefits of GLP-1RA use may extend to prevention for AF in patients with diabetes. Our findings call for future randomized controlled trials to focus on the effects of GLP-1RA on AF prevention.

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Funding

Research reported in this publication was supported by R01 DK115534 and K24 HL155861 (PI: Dr. Grams), and K01 DK121825 (PI: Dr. Shin) from the National Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health. The funding sources had no role in the design and conduct of the study, analysis or interpretation of the data, and preparation or final approval of the manuscript before publication.

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Authors and Affiliations

  1. Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA

    Yunwen Xu PhD, Shoshana H. Ballew PhD, Elizabeth Selvin PhD, MPH, Morgan E. Grams MD, PhD & Jung-Im Shin MD, PhD

  2. Division of Cardiology, Department of Medicine, Hospital of the University of Pennsylvania, Philadelphia, PA, USA

    Thomas A. Boyle MD

  3. Institute for Global Health and Development, Peking University, Beijing, China

    Beini Lyu MD, PhD

  4. Department of Nephrology, Geisinger Health System, Danville, PA, USA

    Alexander R. Chang MD, MS

  5. Division of Nephrology, Department of Internal Medicine, Tufts Medical Center, Boston, MA, USA

    Lesley A. Inker MD, MS

  6. Department of Medicine, New York University Grossman School of Medicine and Langone Health, New York, NY, USA

    Morgan E. Grams MD, PhD

  7. Department of Population Health, New York University Grossman School of Medicine and Langone Health, New York, NY, USA

    Morgan E. Grams MD, PhD

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  1. Yunwen Xu PhD
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Correspondence to Jung-Im Shin MD, PhD.

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Conflict of interest:

A. Chang reports having consultancy agreements with Amgen, Novartis, and Reata; reports receiving research funding from a Novo Nordisk Investigator Sponsored Study; reports having an advisory or leadership role with Reata, Relypsa; and reports having other interests or relationships with National Kidney Foundation grant support and the NKF Patient Network. E. Selvin reports receiving research support from the Foundation for the National Institutes of Health and the National Institutes of Health; reports receiving royalty payments from Wolters Kluwer for chapters and laboratory monographs in UpToDate on measurements of glycemic control and screening tests for type 2 diabetes; and reports having an advisory or leadership role with Diabetes Care and Diabetologia Editorial Board, the American Diabetes Association, and the American Heart Association. L. Inker reports having consultancy agreements with Diamtrix; reports receiving research funding to the institution for research and contracts with the National Institutes of Health, National Kidney Foundation, Omeros, Reata Pharmaceuticals; reports having consulting agreements to her institution with Omeros and Tricida Inc.; reports having an advisory or leadership role with the Alport Syndrome Foundation; and reports having other interests or relationships as a member of the American Society of Nephrology, the National Kidney Disease Education Program, and the National Kidney Foundation. M. Grams reports having an advisory or leadership role with AJKD, CJASN, JASN Editorial Board, KDIGO Executive Committee, NKF Scientific Advisory Board, and the USRDS Scientific Advisory Board; and reports having other interests or relationships with grant funding from NKF, which receives funding from multiple pharmaceutical companies, and grant funding from the National Institutes of Health. J. Shin reports receiving research funding from Merck and the National Institutes of Health. The remaining authors have nothing to disclose.

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Xu, Y., Boyle, T.A., Lyu, B. et al. Glucagon-like peptide-1 receptor agonists and the risk of atrial fibrillation in adults with diabetes: a real-world study. J GEN INTERN MED (2024). https://doi.org/10.1007/s11606-023-08589-3

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