Utilization, Effectiveness, and Safety of SGLT2 Inhibitors Among Patients with Type 2 Diabetes Mellitus

Date of ISAC Approval: 
11/02/2019
Lay Summary: 
Sodium-glucose cotransporter 2 (SGLT2) inhibitors are a new class of antidiabetic drugs used in the treatment of type 2 diabetes. Studies of these drugs in a research setting (clinical trials) have suggested that SGLT2 inhibitors reduce the risk of diseases of the heart or large blood vessels among patients with type 2 diabetes. However, whether the benefits of SGLT2 inhibitors can be obtained in a real-world setting remains uncertain. Furthermore, recent safety concerns have emerged regarding these drugs and potential increased risks of severe infection in the kidneys, ureters, or bladder (urosepsis), increased acidity of the blood (diabetic ketoacidosis), and surgical removal of the leg (lower extremity amputation). Our objective is therefore to examine the utilization, effectiveness, and safety of SGLT2 inhibitors in a real-world setting. To accomplish this objective, we will first describe the use of antidiabetic drugs between 2006 and 2018. We will then compare the rates of cardiovascular events among patients using SGLT2 inhibitors and patients using dipeptidyl peptidase-4 (DPP-4) inhibitors, another class of antidiabetic drugs, between 2013 and 2018. Finally, we will also compare the rates of urosepsis, diabetic ketoacidosis, and lower extremity amputation among the two groups during the same period.
Technical Summary: 
Sodium-glucose cotransporter 2 (SGLT2) inhibitors are a new class of drugs used in the treatment of type 2 diabetes. Clinical trials have suggested that SGLT2 inhibitors reduce the incidence of major adverse cardiac events (MACE) among patients with type 2 diabetes and either established cardiovascular disease or at high cardiovascular risk compared with placebo. However, the effectiveness of SGLT2 inhibitors in a real-world setting remains poorly understood. Furthermore, recent safety concerns have emerged regarding these agents and potential increased risks of severe urinary tract infection (urosepsis), diabetic ketoacidosis (DKA), and lower extremity amputation. Our objective is therefore to examine the utilization, effectiveness, and safety of SGLT2 inhibitors in a real-world setting. To accomplish this objective, we will first describe the use of antidiabetic drugs between 2006 and 2018. Using a prevalent new-user design, we will then conduct a time-conditional propensity score matched analysis comparing users of SGLT2 inhibitors to users of dipeptidyl peptidase-4 (DPP-4) inhibitors for the following outcomes: MACE, the individual components of MACE (myocardial infarction, ischemic stroke, cardiovascular death), and hospitalization for heart failure. In addition, we will create a study cohort of new users of antidiabetic drugs between 2013 and 2018. Cox proportional hazards models will be used to estimate site-specific adjusted hazard ratios and corresponding 95% confidence intervals of the association between SGLT2 and DPP-4 inhibitor use and urosepsis, DKA, and lower extremity amputation. Site-specific results will be combined by random-effects meta-analysis to provide an overall assessment of the effectiveness and safety of SGLT2 inhibitors among patients with type 2 diabetes.
Health Outcomes to be Measured: 
Major adverse cardiac events including myocardial infarction, ischemic stroke, and cardiovascular death Hospitalization for heart failure Urosepsis Diabetic ketoacidosis Lower extremity amputation
Collaborators: 

Samy Suissa - Chief Investigator - McGill University
Antonios Douros - Collaborator - McGill University
Audray St-Jean - Collaborator - Sir Mortimer B Davis Jewish General Hospital
Hui (Hoi) Yin - Collaborator - Sir Mortimer B Davis Jewish General Hospital
Dr Kristian Filion - Collaborator - McGill University
Lisa Lix - Collaborator - University of Manitoba
Oriana Hoi Yun Yu - Collaborator - Sir Mortimer B Davis Jewish General Hospital
Dr Pierre Ernst - Corresponding Applicant - McGill University
Sophie Dell'Aniello - Collaborator - McGill University
Vanessa Brunetti - Collaborator - McGill University

Linkages: 
HES Admitted;ONS;Practice IMD (Standard)