Antihyperglycemic drugs use and new-onset atrial fibrillation: A population-based nested case control study

Abstract

Currently, the potential risk of atrial fibrillation associated with antihyperglycemic drug use has been a topic of considerable interest. However, it remains uncertain whether different classes of antihyperglycemic drug therapy are associated with the risk of atrial fibrillation risk. Here, we investigated the association between different classes of antihyperglycemic drugs and new-onset atrial fibrillation (NAF). A case-matched study was performed based on the National Health Insurance Program in Taiwan. Patients who had NAF were considered the NAF group and were matched in a 1:4 ratio with patients without NAF, who were assigned to the non-NAF group. Patients were matched according to sex, age, diabetes mellitus duration, index date, and Charlson Comorbidity Index score. We used multivariate logistic regression controlling for potential confounders to examine the association between different classes of antihyperglycemic drug use and the risk of NAF. Overall, we identified 2,882 cases and 11,528 matched controls for the study. After adjusting for sex, age, comorbidities, and concurrent medications, users of biguanides or thiazolidinediones were at a lower risk of developing NAF when compared with non-users (odds ratio [OR] 0.81, 95% confidence interval [CI] 0.71–0.95 and OR 0.72, 95% CI 0.63–0.83, respectively). In contrast, users of insulin were at a higher risk of developing NAF than were non-users (OR 1.19, 95% CI 1.06–1.35). Sulfonylureas, glinides, α-glucosidase inhibitors, and dipeptidyl peptidase-4 inhibitors were not associated with developing the risk of NAF. In conclusion, the use of biguanides or thiazolidinediones may be associated with a low risk of NAF, whereas insulin may be associated with a significant increase in the risk of NAF in patients with type 2 diabetes mellitus during long-term follow-up. Further prospective randomized studies should investigate which specific class of antihyperglycemic drug treatment for diabetes mellitus can prevent or postpone NAF.

Do most patients with obesity or type 2 diabetes, and atrial fibrillation, also have undiagnosed heart failure? A critical conceptual framework for understanding mechanisms and improving diagnosis and treatment

“…150 Insulin-related hypoglycaemia may also activate the sympathetic nervous system and promote arrhythmogenesis. 151 Accordingly, insulin use has been accompanied by an increased risk for AF 152,153 and HF 154,155 and an enhanced likelihood of poor outcomes (including stroke) in patients with established HFpEF. 73,156,157…”

Heightened risk of intensive rate control in patients with atrial fibrillation who are obese or have type 2 diabetes: A critical review and re‐evaluation

“…Marked weight loss decreases epicardial fat mass, improves LA geometry, and alleviates the burden of AF . Insulin promotes epicardial adipogenesis and can thereby aggravate the atrial myopathy and stimulate AF . In contrast, drugs used in diabetes that ameliorate the inflammatory state of epicardial fat (eg, statins and metformin) are accompanied by improvement in LA structure and a reduction in the incidence and prevalence of AF .…”

“…[10][11][12][13][14] Insulin promotes epicardial adipogenesis and can thereby aggravate the atrial myopathy and stimulate AF. [15][16][17] In contrast, drugs used in diabetes that ameliorate the inflammatory state of epicardial fat (eg, statins and metformin) are accompanied by improvement in LA structure and a reduction in the incidence and prevalence of AF. [18][19][20][21][22][23] Most importantly, the benefits of bariatric surgery, statins, and metformin on the atrial myopathy have been accompanied by a reduced risk of systemic thromboembolism in both observational studies and randomized trials.…”

Metformin Use is Associated with A Lower Incidence of Hospitalization for Atrial Fibrillation in Patients with Type 2 Diabetes Mellitus

“…Metformin, now a rst-line oral antidiabetic drug recommended for the treatment of type 2 diabetes mellitus, exerts an insulin sensitizing effect [6] and may have anti-in ammatory, anti-aging, anti-cancer and even anti-microbial effects [7][8][9][10]. Two previous pharmacoepidemiological studies conducted in Taiwan that used the nationwide reimbursement database of the National Health Insurance (NHI) showed that patients with type 2 diabetes mellitus treated with metformin might have a 20% lower risk of AF [11,12]. However, these earlier studies suffered from some methodological limitations.…”

“…In the study by Liou et al, a nested case-control design was used by including 11528 diabetes patients without AF and 2882 diabetes patients with AF [12]. The investigators cross-sectionally estimated the odds ratios of AF for metformin users versus metformin non-users [12]. The crosssectional design did not assure a temporal correctness of a cause (metformin use) that should happen before an effect (AF incidence).…”