20 Nov SGLT2 inhibitors and risk of major adverse cardiovascular events (Q18-06)
SGLT2 inhibitors and risk of major adverse cardiovascular events (Q18-06)
Overview
What is the issue?
- Sodium-glucose cotransporter 2 (SGLT2) inhibitors are a new class of drugs used as second- or third-line treatment for type 2 diabetes.
- Randomized controlled trials have demonstrated that SGLT2 inhibitors reduce the risk of major adverse cardiovascular events (MACE) and heart failure among patients with type 2 diabetes. However, their effectiveness in a real-world setting remains uncertain.
What was the aim of the study?
- This study, evaluated the risk of serious cardiovascular events associated with the use of SGLT2 inhibitors compared to the use of dipeptidyl peptidase-4 (DPP-4) inhibitors among patients with type 2 diabetes.
How was the study conducted?
- Our investigators conducted eight population-based cohort studies with health records of over 400,000 patients with type 2 diabetes from seven Canadian provinces and the United Kingdom.
- Patients aged 18 years and older who received a prescription for a SGLT2 inhibitor between 2013 and 2018 were matched to those who received a prescription for a DPP-4 inhibitor (another class of antidiabetic drugs).
- The risk of MACE (a composite endpoint of myocardial infarction, ischemic stroke or cardiovascular death), all-cause mortality, and heart failure were compared in users of SGLT2 inhibitors versus users of DDP-4 inhibitors. Results were combined across studies using a statistical approach called meta-analysis.
What did the study find?
- Over a mean follow-up of 11 months, SGLT2 inhibitors were associated with a relative decrease of 24% in the risk of MACE compared with DPP-4 inhibitors. Results were consistent for the three SGLT2 inhibitors available during the study period.
- Reductions were also observed for the individual endpoints of MACE, all-cause mortality, and heart failure, with more modest benefits for ischemic stroke.
- While these findings suggest that the use of SGLT2 inhibitors is beneficial among patients with type 2 diabetes in a real-word setting, additional studies are needed to determine if these benefits persist long term.
Implications
- This study suggests that SGLT2 inhibitors offer cardiovascular benefits among patients with type 2 diabetes in a real-world setting.
- With consistent results across individual SGLT2 inhibitors, this study suggests a class effect regarding the cardiovascular benefits of SGLT2 inhibitors.
- Additional studies with longer duration of follow-up are needed to determine if these benefits persist long term.
Key message
- SGLT2 inhibitor use was associated with a decreased risk of serious cardiovascular events compared with the use of DPP-4 inhibitors among patients with type 2 diabetes.
Links
Protocol registrationManuscripts
Brunetti VC, St-Jean A, Dell’Aniello S, Fisher A, Yu OHY, Bugden SC, Daigle JM, Hu N, Alessi-Severini S, Shah BR, Ronksley PE, Lix LM, Ernst P, Filion KB; for the Canadian Network for Observational Drug Effect Studies (CNODES) Investigators. Characteristics of new users of recent antidiabetic drugs in Canada and the United Kingdom. BMC Endocr Disord. 2022 Sep 29;22(1):241.
Lix LM, Sobhan S, St-Jean A, Daigle JM, Fisher A, Yu OHY, Dell’Aniello S, Hu N, Bugden SC, Shah BR, Ronksley PE, Alessi-Severini S, Douros A, Ernst P, Filion KB, for the Canadian Network for Observational Drug Effect Studies (CNODES) Investigators. Validity of an Algorithm to Identify Cardiovascular Deaths from Administrative Health Records: A Multi-Database Population-Based Cohort Study. BMC Health Serv Res. 2021 Jul 31;21(1):758.
Filion KB, Lix LM, Yu OHY, Dell’Aniello S, Douros A, Shah BR, St-Jean A, Fisher A, Tremblay E, Bugden SC, Alessi-Severini S, Ronksley PE, Hu N, Dormuth CR, Ernst P, Suissa S for the Canadian Network for Observational Drug Effect Studies (CNODES) Investigators. Sodium glucose cotransporter 2 inhibitors and risk of major adverse cardiovascular events: multi-database retrospective cohort study. BMJ. 2020 Sep 23;370:m3342.
Douros A, Lix LM, Fralick M, Dell’Aniello S, Shah BR, Ronksley PE, Tremblay E, Hu N, Alessi-Severini S, Fisher A, Bugden SC, Ernst P, Filion KB, for the Canadian Network for Observational Drug Effect Studies (CNODES) Investigators. Sodium-glucose co-transporter 2 inhibitors and the risk of diabetic ketoacidosis: A multicenter cohort study. Annals of Internal Medicine. 2020 Sep 15;173(6):417-425.
Yu OHY, Dell’Aniello S, Shah BR, Brunetti V, Daigle JM, Fralick M, Douros A, Hu N, Alessi-Severini S, Fisher A, Bugden SC, Ronksley PE, Filion KB, Ernst P, Lix LM, for the Canadian Network for Observational Drug Effect Studies (CNODES) Investigators. Sodium Glucose Co-transporter-2 Inhibitors and the Risk of Below-knee Amputation: a Multicenter Observational Study. Diabetes Care 2020 Oct;43(10):2444-2452.
Fisher A, Fralick M, Filion KB, Dell’Aniello S, Douros A, Tremblay E, Shah BR, Ronksley PE, Alessi-Severini S, Hu N, Bugden SC, Ernst P, Lix LM, for the Canadian Network for Observational Drug Effect Studies (CNODES) Investigators. Sodium-glucose Cotransporter 2 Inhibitors and the Risk for Urosepsis – A Multi-site Prevalent New-user Cohort Study. Diabetes Obes Metab. 2020 Sep;22(9):1648-1658.