SGLT2 inhibitors and risk of major adverse cardiovascular events (Q18-06)

SGLT2 inhibitors and risk of major adverse cardiovascular events (Q18-06)

Q18-06

Overview

What is the issue?
  • 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 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
  • Sodium-glucose cotransporter 2 (SGLT2) inhibitor use was associated with a decreased risk of serious cardiovascular events compared with the use of dipeptidyl peptidase-4 (DPP-4) inhibitors among patients with type 2 diabetes.

Manuscripts

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.

Presentations

Project Team

Content Expert
Michael Fralick MD, PhD
Content Expert
Oriana Yu MD, MSc
Steering Committee Liaison
Kristian Filion PhD
Research Assistant
Audray St-Jean MSc
Site Investigator
Nianping Hu PhD
Saskatchewan
Site Investigator
Éric Tremblay BPharm, MSc
Quebec
Site Investigator
Baiju Shah MD, PhD
Ontario
Site Investigator
Hala Tamim PhD
Atlantic
Site Investigator
Shawn C. Bugden BSc (Pharm), MSc, PharmD
Atlantic
Site Investigator
Silvia Alessi-Severini BSc (Pharm), PhD
Manitoba
Site Investigator
Vanessa Brunetti MSc
CPRD
Site Investigator
Antonios Douros MD, PhD
CPRD
Site Investigator
Anat Fisher MD, PhD
British Columbia
Site Investigator
Colin R. Dormuth ScD
British Columbia
Site Investigator
Paul Ronksley PhD
Alberta
Analyst
Nianping Hu PhD
Saskatchewan
Analyst
Jean-Marc Daigle MSc
Quebec
Analyst
Fangyun Wu MSc
Ontario
Analyst
Steve Doucette MSc
Atlantic
Analyst
Yan Wang MSc
Atlantic
Analyst
Matthew Dahl BSc
Manitoba
Analyst
Hui Yin MsC
CPRD
Analyst
Jason Kim MPH, BHSc
British Columbia
Analyst
Greg Carney BSc, PhD
British Columbia
Analyst
Jianguo (James) Zhang MSc
Alberta