The sodium-glucose co-transporter 2 (SGLT2) inhibitors are one the newest classes of medications used to treat type 2 diabetes. SGLT2 inhibitors work by limiting the amount of sodium that is reabsorbed back into the body through the kidney. Instead of being reabsorbed back into the body, the extra sugar is excreted in the urine. Although these medications are studied extensively prior to being approved, the extent to which they cause unintended side effects, especially when they are used in real life conditions is not well known. Multiple federal regulatory agencies, such as Health Canada and the US Food and Drug Administration, have published warnings regarding several potential harms. Given the increasing use of SGLT2 inhibitors in the treatment of type 2 diabetes, further evaluation of their post-marketing safety is required. We propose to study the real-world safety of SGLT2 inhibitors using large databases that contain detailed healthcare records for individuals with type 2 diabetes.
Objective: To measure the association between use of the sodium glucose co-transporter (SGLT2) inhibitors for the management of type 2 diabetes and safety outcomes.
Methods: We propose to conduct a series of population-based cohort studies using information from everyday health system encounters. We will quantify the risk of several important safety outcomes among metformin monotherapy initiators who subsequently start a second agent. Within each database, separate cohorts of propensity score matched new users of SGLT2 inhibitors and new users of dipeptidyl peptidase-4 inhibitors will be formed. We will then compare the adjusted population-based rates of: 1) acute kidney injury, 2) composite of new or worsening nephropathy, 3) fragility fractures, 4) composite of lower limb amputations, 5) ketoacidosis, 6) composite of urinary tract infections, 7) composite of genital infections, 8) composite of all-cause mortality and all-cause hospitalizations.
Data analysis: We will use proportional hazards regression models with fixed and time-dependent variables to precisely define both drug exposures and confounders, and to determine if SGLT2 inhibitors are independently associated with a change in risk in these safety outcomes. Analyses will be conducted separately in multiple databases and then each estimate will be combined using random-effects meta-analysis.
Acute Kidney Injury
- Composite of new or worsening nephropathy
- Fragility fractures
- Composite of lower limb amputations
- Ketoacidosis
- Composite of urinary tract infection
- Composite of genital infections
- Composite of all-cause mortality and all-cause hospitalizations
Amendment (April 2022):
- patterns of SGLT-2 inhibitor utilization
JM Gamble - Chief Investigator - University Of Waterloo
JM Gamble - Corresponding Applicant - University Of Waterloo
Arsene Zongo - Collaborator - University of Alberta
Baiju Shah - Collaborator - University of Toronto
Dean Eurich - Collaborator - University of Alberta
Wajd Alkabbani - Collaborator - University Of Waterloo
Wasem Alsabbagh - Collaborator - University Of Waterloo
Baiju Shah - Collaborator - University of Toronto
Dean Eurich - Collaborator - University of Alberta
Wajd Alkabbani - Collaborator - University Of Waterloo
Wasem Alsabbagh - Collaborator - University Of Waterloo
Arsene Zongo - Collaborator - University of Alberta
HES Admitted Patient Care;ONS Death Registration Data;Patient Level Index of Multiple Deprivation