SGLT2 Inhibitors Linked to Reduced Rate of Stroke in Patients with Diabetes and AF

In a study published in the Journal of the American Heart Association, researchers found that the utilization of sodium-glucose cotransporter-2 (SGLT2) inhibitors is linked to reduced risk for stroke among individuals with diabetes and atrial fibrillation (AF). These findings suggest that prioritizing SGLT2 inhibitors as the initial treatment option for patients with diabetes and AF could be taken into consideration.

The researchers recruited patients from National Taiwan University Hospital, aiming to explore the association between SGLT2 inhibitor therapy and the occurrence of embolic events in patients diagnosed with AF and a concomitant diagnosis of diabetes. A cohort of 9116 patients were chosen to participate in the study. They were longitudinally followed for 5 years (January 2016-December 2020) to assess the risk for stroke associated with SGLT2 inhibitors. Patients in the treatment arm received either 25-mg empagliflozin or 10-mg dapagliflozin orally once daily. Stroke risk was assessed by calculating and documenting CHA₂DS₂-VASc scores.

Of the 9116 patients included in this study, 2502 individuals were excluded due to either incomplete follow-up, incomplete drug information, or insufficient clinical data. The propensity-score matched population consisted of 472 patients treated with SGLT2 inhibitors, while 3743 individuals did not receive SGLT2 inhibitors. The average age of participants was 73.2 (SD, 10.5) years, and 61% of patients were men. Baseline characteristics were similar between patients receiving and those not receiving SGLT2 inhibitor therapy.

Findings revealed the stroke rate to be 3.4% (95% CI, 2.8-4.2) patient-years among patients receiving SGLT2 inhibitors, whereas it was 4.3% (95% CI, 4.0–4.6) in patients not receiving SGLT2 inhibitors (P =.021). After adjusting for CHA₂DS₂-VASc score via the multivariable Cox model, patients receiving SGLT2 inhibitors exhibited a 20% reduction in stroke risk (HR, 0.80 [95% CI, 0.64–0.99]; P =.043).

One particular limitation of this study is that it could not be randomized since stroke prevention is not the chief reason SGLT2 inhibitors were prescribed in this study population. Study outcomes are also limited by the lack of differentiation between stroke subtypes. Furthermore, this study exclusively includes participants who consistently maintained the same medication without any changes throughout the follow-up period. Lastly, researchers were unable to provide concrete evidence regarding the mechanism through which SGLT2 inhibitors might prevent stroke specifically stemming from AF.

Current guidelines suggest SGLT2 inhibitors are only to be recommended as a second- or third-line treatment strategy, subsequent to the administration of metformin or sulphonylurea. Study results suggest that for patients with AF and concomitant diabetes, the utilization of SGLT2 inhibitors should be recommended as a first-line treatment strategy over sulphonylurea therapy, considering the potential benefits in primary prevention of embolic stroke.

“…our data were the first to reveal SGLT2i [inhibitors] [are] associated with a lower risk of embolic stroke in comparison with other hypoglycemic therapy,” the study authors wrote. “Our results provided a new direction for the role of SGLT2i in the therapeutic strategy of diabetes”