SGLT2 Inhibitors May Cut Repeat Syncope in Type 2 Diabetes

The study covered in this summary is under consideration at Cardiovascular Diabetology and was published on as a preprint and has not yet been peer reviewed.

Key Takeaways

  • Patients with type 2 diabetes and a recent history of recurrent vaso-vagal syncope (VVS) treated with a sodium-glucose cotransporter 2 (SGLT2) inhibitor had significantly fewer VVS recurrences during 1-year follow-up compared with similar patients not on a drug from this class in a prospective, multicenter, Italian study with 607 patients.

  • Use of SGLT2 inhibitors appeared to lessen cardiac autonomic dysfunction, possibly linked to class effects on the systemic and cardiac sympathetic axis.

Why This Matters

  • SGLT2 inhibitors appear promising for preventing recurrent VVS recurrence in patients with type 2 diabetes.

  • This is the first reported study to investigate whether chronic SGLT2 inhibitor treatment may reduce the risk of recurrent VVS in patients with type 2 diabetes.

  • The apparent preventive effect of agents from the SGLT2 inhibitor class in the studied patients is important because VVS recurrence is higher in patients with type 2 diabetes, and type 2 diabetes is an independent predictor of VVS recurrence.

Study Design

  • The SCAN study prospectively enrolled 607 adults with type 2 diabetes — 161 patients who used SGLT2 inhibitors for at least 6 months before enrollment and 446 patients who did not — who had a VVS episode during a clinically indicated head-up tilt-table test at any of six hospitals in Naples, Rome, and Campobasso, Italy, during June 2018-March 2021.

  • The 607 patients with type 2 diabetes who entered the study came from a cohort of 4794 patients (of whom 618 had type 2 diabetes) who underwent a clinically indicated tilt-table test during the study period because they had experienced at least two VVS events during the 6 months prior to their test.

  • At enrollment and a year later the patients underwent a series of blood, cardiac, and neurological tests and examinations.

  • Study outcomes measured at enrollment and after 1 year compared the patients receiving an SGLT2 inhibitor and those not on one of these agents for heart rate variability, using myocardial scintigraphy to assess cardiac sympathetic nerve activity, and VVS recurrence.

Key Results

  • Patients treated with an SGLT2 inhibitor at entry had a significant (45%) reduction in their incidence of VVS during 1-year follow-up compared with the patients not on SGLT2 inhibitor treatment in a Cox multiple regression analysis that included multiple potential demographic and clinical confounders, including age, smoking status, body mass index, heart rate, and beta blocker use.

  • At baseline and 1-year follow-up, compared with SGLT2 inhibitor users, nonusers had higher levels of inflammatory markers and catecholamines, worse glycemic control, and more autonomic system dysfunction.

  • Patients on an SGLT2 inhibitor received either of two different dosages of empagliflozin (Jardiance), or a single dosage of canagliflozin (Invokana). All three subgroups showed similar rates of reduced cardiovascular outcomes at 1 year compared with the patients not receiving an SGLT2 inhibitor.


  • The incidence of syncope recurrence may be different with different follow-up times.

  • The study did not use continuous monitoring to systematically record all VVS recurrences.

  • The study did not assess cardio-protective or anti-inflammatory effects of treatment with an SGLT2 inhibitor.

  • The study relied on measurement of plasma norepinephrine levels as a gauge of systemic sympathetic activity.

  • The scope of the study prevents a definitive conclusion on the correlation between treatment with an SGLT2 inhibitor and VVS recurrence.


  • The study did not receive commercial funding.

  • The authors report no disclosures.

This is a summary of a preprint research study , “SGLT2-inhibitors modulate the Cardiac Autonomic Neuropathy and reduce the vaso-vagal syncope recurrence in patients with type 2 diabetes mellitus: the SCAN study,” written by researchers primarily at the University of Campania “Luigi Vanvitelli”, Caserta, Italy, and at other centers in Italy. Preprints from are provided to you by Medscape. This study has not yet been peer reviewed. The full text of the study can be found on

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