Dipeptidyl peptidase-4 inhibitor decreases the risk of atrial fibrillation in patients with type 2 diabetes: a nationwide cohort study in Taiwan

Abstract

BackgroundWhether dipeptidyl peptidase-4 inhibitor (DPP4i) is associated with a lower risk of new-onset atrial fibrillation (AF) in patients with diabetes remains unclear. This study aimed to evaluate the risk of AF associated with use of DPP4i among a longitudinal cohort of patients with diabetes.MethodsOver a 3-year period, 480,000 patients with diabetes were analyzed utilizing Taiwan’s National Health Insurance Research Database and 90,880 patients taking metformin as first-line therapy were enrolled. Patients were further divided into two groups: (1) DPP4i users: those taking DPP4i and (2) non-DPP4i users: those prescribed other hypoglycemic agents (HAs) as second-line drug. Study end point was defined by diagnosis of AF, addition of any third-line HA, or the end of the study period (December 31, 2013), whichever came first.ResultsA total of 16,017 DPP4i users and 74,863 non-DPP4i users were eligible for the study. For the DPP4i group, most patients were prescribed sitagliptin (n = 12,180; 76%). Among the non-DPP4i group, most patients took sulfonylurea (n = 60,606; 81%) as their second-line medication. DPP4i users were associated with a lower risk of new-onset AF compared with non-DPP4i users after propensity-score weighting (hazard ratio 0.65; P < 0.0001). Subgroup analysis showed that DPP4i user were associated with a lower risk of new-onset AF compared with non-DPP4i users in most subgroups. Multivariate analysis indicated that use of DPP4i was associated with lower risk of new-onset AF and age > 65 years, presence of hypertension, and ischemic heart disease were independent risk factors for new-onset AF.ConclusionsAmong patients with diabetes prescribed with metformin, the patients with DPP4i as second HA were associated with a lower risk of AF compared with the patients with other drugs as second HAs in real-world practice.Electronic supplementary materialThe online version of this article (10.1186/s12933-017-0640-5) contains supplementary material, which is available to authorized users.

Atrial fibrillation and type 2 diabetes: Prevalence, etiology, pathophysiology and effect of anti‐diabetic therapies

“…However, because of the widespread use of sulfonylureas and meglitinide in the comparison group, these results could be interpreted as representing an increase in NAF with use of secretagogues. The incidence of NAF with use of sulfonylureas was increased by 45% (HR, 1.45; 95% CI, 1.24–1.720; P = 0.0001) and with use of meglitinide by 178% (HR, 2.78; 95% CI, 2.05‐3.76; P = 0.0001) . A nested, case‐control study in patients over 65 years of age revealed a significant relationship between the use of certain antihyperglycaemic drugs and NAF.…”

“…The incidence of NAF with use of sulfonylureas was increased by 45% (HR, 1.45; 95% CI, 1.24-1.720; P = 0.0001) and with use of meglitinide by 178% (HR, 2.78; 95% CI, 2.05-3.76; P = 0.0001). 67 A nested, case-control study in patients over 65 years of age revealed a significant relationship between the use of certain antihyperglycaemic drugs and NAF. After adjusting for age, sex, comorbidities and concurrent medication, the risk was higher among insulin users than among non-users (OR, 1.58; 95% CI, 1.37-1.82).…”

Pharmacological Inhibition of Serine Proteases to Reduce Cardiac Inflammation and Fibrosis in Atrial Fibrillation

“…Block of PAR-1 signaling Oral anti-platelet agent Unknown DPP-4 inhibitors (Lendeckel, 2001;Tremblay, 2014;Wronkowitz, 2014;Gong et al, 2015;Yamamoto, 2015;Chang, 2017;Zhang, 2017;Igarashi, 2018) Sitagliptin, saxagliptin and other gliptins…”

“…Also, soluble DPP-4 can activate PAR-2 in vascular smooth muscle cells, leading to production of pro-inflammatory cytokines (Wronkowitz, 2014). Recent work suggested that circulating and/or locally expressed DPP4 plays a role in AF pathogenesis (Lendeckel, 2001;Yamamoto, 2015;Chang, 2017;Zhang, 2017;Igarashi, 2018). A recent observational study revealed that diabetic patients treated with DPP4 inhibitors (gliptins) had a lower risk of AF as compared with patients treated with other drugs (Chang, 2017).…”

Research update for articles published in EJCI in 2017

“…We had earlier demonstrated that patients who were administered dipeptidyl peptidase 4 (DPP4) inhibitors had a lower risk of developing new‐onset atrial fibrillation (NAF) than nonusers among the elderly . Simultaneously, another research group in Taiwan from which they identified 16 017 patients in the cohort of DPP4 inhibitor users and 74 863 patients in the cohort of DPP4 inhibitor nonusers and reported that DPP4 inhibitor therapy is associated with a decreased risk of developing NAF . However, another study identified 401 linagliptin users who had acute coronary syndrome or acute ischaemic stroke and 802 controls (matched with patient characteristics, baseline comorbidities, medication prescribed 90 days since indexed hospitalization and index year and month by propensity score) .…”