What is the clinical evidence from this study?

Study design: Cohort. Population: Type 2 diabetes mellitus (n=27989). Intervention: Sodium glucose cotransporter 2 inhibitors (SGLT2i) vs. Dipeptidyl peptidase-4 inhibitors (DPP4i). Primary outcome: New-onset atrial fibrillation (HR 0.61, 95% CI 0.50-0.73, p=<0.001).

November 6, 2020Open Access

The risk of new-onset atrial fibrillation in patients with type 2 diabetes mellitus treated with sodium glucose cotransporter 2 inhibitors versus dipeptidyl peptidase-4 inhibitors

Q: What are the key findings of this study?

SGLT2i use was associated with a significantly lower risk of new-onset atrial fibrillation compared with DPP4i in patients with type 2 diabetes mellitus (HR 0.61).

Key Result

SGLT2i use was associated with a significantly lower risk of new-onset atrial fibrillation compared with DPP4i in patients with type 2 diabetes mellitus (HR 0.61).

Study Design

Type

Cohort (n=27,989)

Multicenter

Yes

Structured PICO

Does SGLT2i reduce the risk of new-onset atrial fibrillation in patients with type 2 diabetes mellitus compared to DPP4i?

Population

27,989 patients with type 2 diabetes mellitus from a multi-center healthcare provider in Taiwan

Intervention

Sodium glucose cotransporter 2 inhibitors (SGLT2i) (empagliflozin 55%, dapagliflozin 45%, canagliflozin 0%)

Comparator

Dipeptidyl peptidase-4 inhibitors (DPP4i) (linagliptin 51%, sitagliptin 24%, saxagliptin 13%, vildagliptin 8%, alogliptin 5%)

Outcome

New-onset atrial fibrillationhard clinical

In patients with type 2 diabetes, treatment with SGLT2 inhibitors is associated with a significantly lower risk of developing new-onset atrial fibrillation compared to DPP4 inhibitors.

Main Result

Effect estimate: HR 0.61 (95% CI 0.50-0.73)

p-value: p=<0.001

Limitations

Lack of serial ECG data to differentiate persistent or paroxysmal AF
Unmeasured confounding factors such as physicians' choice of medications, tobacco/alcohol use, and family history
Lack of long-term outcome comparisons (e.g., 5 or 10 years of follow-up)
Retrospective and observational study design
Closed medical system without external link, potentially resulting in loss to follow-up
On-treatment design did not account for changes in medical status or activity during follow-up
Limited number of patients treated with canagliflozin
Study only investigated Asian patients, limiting generalizability to other races

Abstract

Abstract Background Sodium glucose cotransporter 2 inhibitor (SGLT2i) reduces the risk of hard cardiovascular endpoints in type 2 diabetes mellitus (T2DM) patients with/without established cardiovascular diseases. Whether SGLT2i is associated with a lower risk of new-onset atrial fibrillation (AF) in T2DM patients is unclear. We aimed to evaluate the risk of new-onset AF associated with the use of SGLT2i compared to dipeptidyl peptidase-4 inhibitor (DPP4i) among a longitudinal cohort of diabetic patients. Methods We used medical data from a multi-center healthcare provider in Taiwan, which included a total of 15,606 and 12,383 patients treated with SGLT2i and DPP4i, respectively, from June 1, 2016 to December 31, 2018. We used propensity-score weighting to balance covariates across study groups. Patients were followed up from the drug index date until the occurrence of new-onset AF, discontinuation of the index drug, or the end of the study period, whichever occurred first. Results Overall, 55%, 45%, and 0% of the patients were treated with empagliflozin, dapagliflozin, and canagliflozin, respectively. Most patients in the DPP4i group were prescribed with linagliptin (51%), followed by sitagliptin (24%), saxagliptin (13%), vildagliptin (8%) and alogliptin (5%). The use of SGLT2i was associated with a lower risk of new-onset AF compared with DPP4i after propensity-score weighting [hazard ratio: 0.61; 95% confidential interval: 0.50–0.73; P ≥ 8%, and chronic kidney disease. The advantage of SGLT2i over DPP4i persisted with different SGLT2i (dapagliflozin or empagliflozin) and either low- or standard-dose SGLT2i. Conclusions SGLT2i was associated with a lower risk of new-onset AF compared with DPP4i among T2DM patients in real-world practice.

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