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February 2, 2026Cardiovascular Diabetology0 citationsOpen Access

Comparative effects of second-line oral antidiabetic medications on atrial fibrillation risk in patients with type 2 diabetes: a nationwide retrospective cohort study

GHGa Young HeoSHSeok-Jae HeoBKB M Ko

Key Result

Thiazolidinediones (SHR 1.22), DPP-4 inhibitors (SHR 1.14), and sulfonylureas (SHR 1.20) were associated with a significantly higher risk of incident atrial fibrillation compared to SGLT2 inhibitors in patients with type 2 diabetes.

Key Points

  • The research aims to compare the effects of second-line oral antidiabetic medications on the risk of atrial fibrillation in type 2 diabetes patients.
  • Retrospective cohort study design
  • Comparison of SGLT2 inhibitors, thiazolidinediones, DPP-4 inhibitors, and sulfonylureas
  • Analysis of atrial fibrillation risk associated with different medications
  • SGLT2 inhibitor use linked to lower atrial fibrillation risk
  • Compared to thiazolidinediones, DPP-4 inhibitors, and sulfonylureas
  • Significant difference in risk reduction observed

Study Design

Type

Cohort (n=36,744)

Structured PICO

Does the use of SGLT2 inhibitors compared to other second-line antidiabetic medications reduce the risk of incident atrial fibrillation in patients with type 2 diabetes?

P
Population
36,744 adults (aged ≥19 years) with type 2 diabetes who simultaneously initiated metformin and a second-line oral antidiabetic medication, mean age 55.3 years, 33.6% female. Excluded: prior atrial fibrillation, history of valvular disease, history of pacemaker or implantable cardioverter-defibrillator insertion, or prior use of antiarrhythmic drugs or anticoagulation therapy.
I
Intervention
SGLT2 inhibitors added to metformin
C
Comparator
Thiazolidinediones, DPP-4 inhibitors, or sulfonylureas added to metformin (exact matched 1:1:5:5 by sex and age categories, with inverse probability of treatment weighting)
O
Outcome
Incident atrial fibrillation (AF) analyzed using a Fine-Gray model treating all-cause mortality as a competing riskhard clinical

In patients with type 2 diabetes, initiating SGLT2 inhibitors as a second-line therapy is associated with a significantly lower risk of incident atrial fibrillation compared to thiazolidinediones, DPP-4 inhibitors, and sulfonylureas.

Main Result

Effect estimate: SHR 1.22 (95% CI 1.09-1.36)

Absolute Event Rate: 3.53% vs 2.98%

p-value: p=<0.001

Limitations

  • Retrospective observational design cannot establish causality and residual confounding may remain.
  • Diagnoses of atrial fibrillation and comorbidities were based on claims records, introducing potential misclassification.
  • Lack of data on glycemic control or diabetes-related complications such as hypoglycemia.
  • Patients who added or switched second-line antidiabetic medications during follow-up could not be fully captured.
  • Potential interactions between metformin and other antidiabetic medications cannot be entirely excluded.
  • Limited generalizability because the sample size decreased substantially after exact matching.

Abstract

This study showed that SGLT2 inhibitor use was associated with a significantly lower risk of AF than use of thiazolidinediones, DPP-4 inhibitors, and sulfonylureas.

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Cite This Study

Heo et al. (2026) conducted a cohort in Type 2 diabetes (n=36,744). Thiazolidinediones vs. SGLT2 inhibitors was evaluated on Incident atrial fibrillation (SHR 1.22, 95% CI 1.09-1.36, p=<0.001). Thiazolidinediones (SHR 1.22), DPP-4 inhibitors (SHR 1.14), and sulfonylureas (SHR 1.20) were associated with a significantly higher risk of incident atrial fibrillation compared to SGLT2 inhibitors in patients with type 2 diabetes.

synapsesocial.com/papers/6980fd60c1c9540dea80f17fhttps://doi.org/10.1186/s12933-025-03024-9
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