20 Nov SGLT2 inhibitors and risk of amputation (Q18-10)
SGLT2 inhibitors and risk of amputation (Q18-10)
Overview
What is the issue?
- Sodium-glucose cotransporter 2 (SGLT2) inhibitors are a new class of drugs used in the second- or third-line treatment of type 2 diabetes.
- However, several safety concerns related with the use of SGLT2 inhibitors have been raised including a potential increased risk of amputation.
What was the aim of the study?
- This study, evaluated the risk of below-knee amputation associated with the use of SGLT2 inhibitors compared to the use of dipeptidyl peptidase-4 (DPP-4) inhibitors.
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.
- Cohorts included patients aged 18 years and older who received a prescription for a SGLT2 inhibitor or a DPP-4 inhibitor between 2013 and 2018.
- The risk of incident below-knee amputation 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?
- During a mean exposed follow-up time of 11 months, there was no evidence of an association between the use of SGLT2 inhibitors and incident below-knee amputation compared with the use of DDP-4 inhibitors among patients with type 2 diabetes.
- Similar findings were observed for each of the three individual SGLT2 inhibitor molecules available during the study period.
- While these findings provide reassurance as to the risk of below-knee amputation with SGLT2 inhibitors in a real-world setting, studies with longer duration of follow-up are needed to assess potential long-term effects.
- CNODES has the ability to analyze a large amount of anonymous patient data to reliably assess questions of drug safety and effectiveness.
Implications
- These findings provide reassurance regarding the risk of below-knee amputation with SGLT2 inhibitors in a real-world setting.
- However, studies with longer duration of follow-up are needed to assess potential long-term effects.
Key message
- SGLT2 inhibitor use was not associated with an increased risk of incident below-knee amputation compared to 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.