SGLT2 inhibitors and risk of diabetic ketoacidosis (Q18-11)

SGLT2 inhibitors and risk of diabetic ketoacidosis (Q18-11)

Q18-11

Overview

What is the issue?
  • SGLT2 inhibitors and DPP-4 inhibitors are newer classes of antidiabetic drugs used as second- or third-line treatments in the management of type 2 diabetes.
  • However, several safety concerns related with the use of SGLT2 inhibitors have been raised including a potentially increased risk of DKA.
What was the aim of the study?
  • This study, evaluated the risk of DKA associated with the use of SGLT2 inhibitors compared to the use of DPP-4 inhibitors.
How was the study conducted?
  • CNODES investigators conducted eight population-based cohort studies with electronic health records of over 400,000 patients with type 2 diabetes from seven Canadian provinces and the United Kingdom.
  • Cohorts included patients aged 18 years and older who received a prescription for an SGLT2 inhibitor or a DPP-4 inhibitor between 2013 and 2018.
  • The risk of DKA was 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?
  • The use of SGLT2 inhibitors was associated with an almost three-fold relative increase in the risk of DKA compared with DPP-4 inhibitors. This increased risk was observed for each of the three SGLT2 inhibitor molecules (canagliflozin, dapagliflozin, empagliflozin) available during the study period.
  • Given the rapidly increasing use of SGLT2 inhibitors in patients with type 2 diabetes, physicians should be aware of DKA as a potential adverse effect.
  • CNODES has the ability to analyze a large amount of anonymous patient data to reliably assess questions of drug safety and effectiveness. The results of this study are an important addition to previous research.
Implications
  • These findings provide evidence of an increased risk of DKA with SGLT2 inhibitors in a real-world setting.
  • Physicians should be aware of DKA as a potential adverse effect when prescribing SGLT2 inhibitors.
Key message
  • Sodium-glucose cotransporter 2 (SGLT2) inhibitor use was associated with an increased risk of diabetic ketoacidosis (DKA) compared to 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