SGLT2 inhibitors and risk of severe urinary tract infection (Q18-09)
What is the issue?
- SGLT2 inhibitors and DPP-4 inhibitors are new classes 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 severe UTI.
What is the aim of the study?
- This study, evaluated the risk of severe UTI associated with the use of SGLT2 inhibitors compared to the use of DPP-4 inhibitors, a class of diabetes medications not thought to cause severe UTI.
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 severe UTI 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 a relative decrease of 42% in the risk of severe UTI compared with DPP-4 inhibitors. Similar reductions were observed for each of the three SGLT2 inhibitor molecules available during the study period.
- These findings provide reassurance as to the risk of severe UTI with SGLT2 inhibitors among patients with type 2 diabetes in a real-world setting. However, given the rapidly increasing use of this medication class, physicians should be aware of severe UTI as a potential adverse effect.
- CNODES has the ability to analyze a large amount of anonymous patient information to reliably assess questions of drug safety and effectiveness.
- These findings provide reassurance regarding the risk of severe UTI with SGLT2 inhibitors in a real-world setting.
- Additional studies with longer duration of follow-up are needed to assess potential long-term effects.
- Sodium-glucose cotransporter 2 (SGLT2) inhibitor use was not associated with an increased risk of severe urinary tract infection (UTI) compared to use of dipeptidyl peptidase-4 (DPP-4) inhibitors among patients with type 2 diabetes.
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.