Original Title: État des pratiques: prévention d’événements cardiovasculaires et innocuité des inhibiteurs du SGLT2 comparativement aux inhibiteurs de la DPP-4 en contexte réel chez les personnes atteintes de diabète de type 2

Authors' objectives: Sodium-glucose cotransporter 2 (SGLT2) inhibitors are a novel class of oral antidiabetics. Randomized controlled trials have shown that they reduce the risk of major adverse cardiovascular events (MACE) in patients with type 2 diabetes. A number of safety advisories concerning their use have been issued, specifically with regard to an increased risk of severe urinary tract infection, diabetic ketoacidosis and lower extremity amputation. However, the risk of cardiovascular events and the safety associated with the use of these inhibitors in a real-world setting remain uncertain.

Authors' results and conclusions: RESULTS: A total of 2,175,815 antidiabetic users were identified for the period from January 1, 2016 to June 30, 2018, including 166,722 new SGLT2 inhibitor users and 194,070 new DPP-4 inhibitor users. Among SGLT2 users, 36.0% initiated treatment with empagliflozin, 33.4% with dapagliflozin and 30.6% with canagliflozin. The proportions of new DPP-4 and new SGLT2 users were generally similar across the jurisdictions. Certain differences in the new users’ characteristics were observed between the three classes of antidiabetics and between the jurisdictions involved. In all, 209,867 new SGLT2 users were matched to 209,867 DPP-4 users. A decrease in the risk of MACE was observed in the patients receiving an SGLT2 inhibitor compared with those receiving a DPP-4 inhibitor (HR: 0.76; 95% CI: 0.69-0.84). A decreased risk was also observed for all-cause mortality (HR: 0.60; 95% CI: 0.54-0.67) and hospitalizations for heart failure (HR: 0.43; 95% CI: 0.37-0.51). Comparable results were obtained for each of the individual MACE endpoints. A decreased risk of urosepsis was observed in patients receiving an SGLT2 inhibitor compared to those receiving a DPP-4 inhibitor (HR: 0.58; 95% CI: 0.42-0.80). The crude incidence rate of Fournier's gangrene was similar in the SGLT2 and DPP-4 users (0.08 versus 0.14 per 1,000 person-years). Additionally, the use of an SGLT2 inhibitor was associated with an increased risk of diabetic ketoacidosis compared to the use of a DPP-4 inhibitor (HR: 2.85; 95% CI: 1.99-4.08). However, no difference between these two classes of drugs was observed for the risk of lower extremity amputation (HR: 0.88; 95% CI: 0.71-1.09). CONCLUSIONS: In this large, multicentre retrospective cohort study, the use of an SGLT2 inhibitor was associated with a decreased risk of MACE relative to the use of a DPP-4 inhibitor in patients with type 2 diabetes. Comparable results were observed for the individual MACE endpoints, all-cause mortality, and heart failure. The use of an SGLT2 inhibitor was also associated with a decreased risk of urosepsis but an increased risk of diabetic ketoacidosis. No significant differences were found between the SGLT2 users and DPP-4 users in terms of lower extremity amputations.

Authors' methods: A multicentre retrospective cohort study was conducted using medical administrative databases from seven Canadian provinces and the UK Clinical Practice Research Datalink clinical database. The use of the three novel classes of antidiabetic drugs, dipeptidyl peptidase-4 (DPP-4) inhibitors, SGLT2 inhibitors and glucagon-like peptide-1 (GLP-1) agonists, is described for new users between 2016 and 2018. A methodological approach including both incident and prevalent new users was used to compare SGLT2 inhibitors with DPP-4 inhibitors in terms of the risk of cardiovascular events and the safety associated with their use. SGLT2 users were matched to DPP-4 users based on the nearest propensity score and a comparable level of diabetes treatment. The primary endpoint was MACE, defined as a composite of myocardial infarction, ischemic stroke, or cardiovascular death. The secondary endpoints included each of the individual MACE endpoints in addition to all-cause mortality and hospitalization for heart failure. The secondary endpoints for evaluating safety were urosepsis, diabetic ketoacidosis, and lower extremity amputation. A cohort was created for all the cardiovascular endpoints and for each of the three safety endpoints. The incidence of Fournier's gangrene was evaluated descriptively. A Cox proportional risk model was used to estimate the adjusted hazard ratios (aHRs) and their 95% confidence intervals (CIs) comparing the use of SGLT2 inhibitors with that of DPP-4 inhibitors using an as-treated approach. Analyses were performed for each endpoint and for each of the participating jurisdictions. The results from the seven Canadian provinces and those from the United Kingdom were then pooled using random-effects meta-analysis.

Project Status: Completed

URL for project: https://www.inesss.qc.ca/publications/repertoire-des-publications/publication/prevention-devenements-cardiovasculaires-et-innocuite-des-inhibiteurs-du-sglt2-comparativement-aux-inhibiteurs-de-la-dpp-4-en-contexte-reel-chez-les-personnes-atteintes-de-diabete-de-type-2.html

Year Published: 2020

URL for published report: https://www.inesss.qc.ca/publications/repertoire-des-publications/publication/prevention-devenements-cardiovasculaires-et-innocuite-des-inhibiteurs-du-sglt2-comparativement-aux-inhibiteurs-de-la-dpp-4-en-contexte-reel-chez-les-personnes-atteintes-de-diabete-de-type-2.html

English language abstract: An English language summary is available

Publication Type: Other

Country: Canada

Province: Quebec

Organisation Name: Institut national d'excellence en sante et en services sociaux

Contact Address: L'Institut national d'excellence en sante et en services sociaux (INESSS) , 2021, avenue Union, bureau 10.083, Montreal, Quebec, Canada, H3A 2S9;Tel: 1+514-873-2563, Fax: 1+514-873-1369

Contact Name: demande@inesss.qc.ca

Contact Email: demande@inesss.qc.ca

Copyright: Gouvernement du Québec