Sodium-glucose cotransporter 2 (SGLT2) inhibitors represent the newest class of medication in the management of type 2 diabetes (a condition characterized by elevated blood sugar levels). They have been widely adopted in clinical practice due to their ability to prevent major adverse cardiovascular events. This is an endpoint that includes heart attacks, strokes, and heart-related death. However, the mechanism responsible for the reduced risk of heart-related death remains unclear. Recent studies suggest that SGLT2 inhibitors might achieve this by reducing the risk of ventricular arrhythmia (VA), a heart rhythm disorder that can be fatal.
We will conduct a study that compares the occurrence of VA among patients with type 2 diabetes who use SGLT2 inhibitors to the occurrence among patients who use dipeptidyl peptidase-4 (DPP-4) inhibitors (another drug class used to treat type 2 diabetes) to assess whether SGLT2 inhibitors reduce VA. We will also compare the risks of fatal VA and cardiac arrest (when the heart stops beating) among patients using these medications. We will also determine if results vary by age, sex, duration of treated type 2 diabetes, history of heart disease, glycated haemoglobin A1c level (a measure of blood sugar control), and user type (new users vs users who have been using the medication). We will also determine if there is a duration-response association between the use of SGLT2 inhibitors and DPP-4 inhibitors and the risk of VA.
Despite the established reduction in cardiovascular death associated with sodium glucose co-transporter 2 (SGLT2) inhibitors, the mechanism responsible for this effect remains unclear. Recent studies indicate that SGLT2 inhibitors may reduce the risk of atrial fibrillation, implying a potential positive influence on heart rhythm. However, their effects on ventricular arrhythmic (VA), another type of fatal heart rhythm disorder, remains poorly understood.
We will conduct a population-based cohort study using a prevalent new user approach and data from the United Kingdom Clinical Practice Research Datalink (CPRD) Aurum, Hospital Episode Statistics, and Office for National Statistics. We will include patients with type 2 diabetes who received a SGLT2 or dipeptidyl peptidase-4 (DPP-4) inhibitor between January 1, 2013, and December 31, 2022. In the primary analysis, exposure will be defined using an as-treated definition in which patients will be followed until VA, departure from the CPRD, death, end of the study period, or treatment discontinuation. The primary analysis will use Cox proportional hazards models to estimate hazard ratios for VA with SGLT2 inhibitors vs DPP-4 inhibitors. Secondary analyses will compare the risks of fatal VA and cardiac arrest between the two groups. We will examine if age, sex, duration of treated type 2 diabetes, history of cardiovascular disease, glycated haemoglobin level, and user type modify our primary estimates. We will also assess if there is a duration-response association between the use of these medications and the risk of VA. To minimize confounding, SGLT2 inhibitor users will be matched to DPP-4 inhibitor users 1:2 on age, sex, and duration of treated diabetes without replacement on nearest time conditional propensity score in chronological order.
Ventricular arrhythmia (fatal or non-fatal) and cardiac arrest (fatal or non-fatal).
Samy Suissa - Chief Investigator - Sir Mortimer B Davis Jewish General Hospital
Kristian Filion - Corresponding Applicant - McGill University
Antonios Douros - Collaborator - McGill University
Oriana Hoi Yun Yu - Collaborator - Sir Mortimer B Davis Jewish General Hospital
pauline reynier - Collaborator - Sir Mortimer B Davis Jewish General Hospital
Robert Platt - Collaborator - McGill University
WANG-CHOI TANG - Collaborator - McGill University
HES Admitted Patient Care;ONS Death Registration Data