Determinants for Use of GLP-1 Receptor Agonists in Canada

Study type

• Study topic:
  Human medicinal product
• Study type:
  Non-interventional study
• Scope of the study:
  Drug utilisation
• Data collection methods:
  Secondary use of data

Non-interventional study

• Non-interventional study design:
  Cohort

Study drug and medical condition

• Medicinal product name, other:
  glucagon-like peptide-1 receptor agonists (GLP-1 RAs)
• Study drug International non-proprietary name (INN) or common name:
  EXENATIDE

  LIRAGLUTIDE

  LIXISENATIDE

  DULAGLUTIDE

  SEMAGLUTIDE

  TIRZEPATIDE
• Anatomical Therapeutic Chemical (ATC) code:
  (A10BJ01) exenatide

  exenatide

  (A10BJ02) liraglutide

  liraglutide

  (A10BJ03) lixisenatide

  lixisenatide

  (A10BJ05) dulaglutide

  dulaglutide

  (A10BJ06) semaglutide

  semaglutide

  (A10BX16) tirzepatide

  tirzepatide

  (A10AE54) insulin glargine and lixisenatide

  insulin glargine and lixisenatide

  (A10AE56) insulin degludec and liraglutide

  insulin degludec and liraglutide

Population studied

• Short description of the study population:
  The study population will include all patients (≥ 66 years in Ontario) who received a dispensation for a GLP-1 RA between 2015 and 2025.
• Age groups:
  • Paediatric Population (< 18 years)
  • Adult and elderly population (≥18 years)

Study design details

• Study design:
  Retrospective cohort study
• Main study objective:
  This study is a replication of a DARWIN EU study (EUPAS1000000828) using data from 6 Canadian provinces. The study has the following objectives:; 1. To determine the incidence and prevalence of prescriptions of the GLP-1 RA medicines (overall, by ingredient, by brand [pre-defined]) during the last 10 years of available data, stratified separately by age, sex, indications (T2DM, obesity, weight management intent) [only for incidence] and prescriber specialty (where available) [only for incidence], and by calendar month in each of the provinces.; 2. To characterize new drug users of GLP-1 RA medicines (overall and stratified by ingredient, by brand, by indication cohorts [T2DM, obesity, weight management intent]) by age, sex, highest strength, and a list of prespecified indications/comorbidities and related co-medications for each province. Characterization will be done over the whole study period and by calendar year.; 3. To describe GLP-1 RA switching of substances (exenatide, liraglutide, lixisenatide, dulaglutide, semaglutide, or tirzepatide cohorts) among new GLP-1 RA users for each province [overall study period] overall and by indication cohorts. ; 4. To describe GLP-1 RA within-substance switching of strength (limited to pre-defined cohorts of strength-levels, with brands when available, for liraglutide, dulaglutide, semaglutide, and tirzepatide) among new users of the respective medicine in each province [overall study period]. ; 5. To describe GLP-1 RA switching of substances (exenatide, liraglutide, lixisenatide, dulaglutide, semaglutide or tirzepatide cohorts) among new GLP-1 RA users for each province between 2015–2020 and annually between 2021 and 2025, overall and by indication cohorts. ; 6. To describe GLP-1 RA within-substance switching of strength (limited to pre-defined cohorts of strength-levels, with brands when available, for liraglutide, dulaglutide, semaglutide, and tirzepatide) among new users of the respective medicine in each province between 2015–2020 and annually between 2021 and 2025.
• Setting:
  We will be using routinely collected health data from 6 Canadian provinces (Nova Scotia, Ontario, Manitoba, Saskatchewan, Alberta, and British Columbia). The study period will be January 1, 2015, to December 31, 2025 (or the latest date of data availability in each province). To maintain consistency with the DARWIN EU study, the primary analyses will be restricted to patients receiving GLP-1 RA prescriptions reimbursed through provincial public drug plans. For these analyses, the study period will begin on September 1, 2019, corresponding to the earliest date that the first GLP-1 RA was added on the provincial formulary across provinces. In addition, secondary analyses will be conducted using all available GLP-1 RA dispensations, including publicly and privately reimbursed claims, as well as those paid out-of-pocket by patients. These analyses will be conducted for objectives 1 to 3 and 5 in all provinces except Ontario, where only public claims are captured.; In each province, the study population will include all individuals (≥ 66 years in Ontario) with a dispensation for a GLP-1 RA during the study period. For incident users (new users), a minimum of 365 days of data availability with no dispensation of the respective GLP-1 RA will be required. For objectives 3 and 5, no use of any GLP-1 RA in the prior year will be required. We will exclude individuals with missing data on date of birth or sex.; The date of the GLP-1 RA dispensing (prevalent users) or first new dispensing of a GLP-1 RA (incident users) will be the cohort entry date. Follow-up will end at the earliest of: loss to follow-up, death, or end of the observation period (latest available data). Follow-up will additionally be censored when switching to another antidiabetic drug class or discontinuing not followed by another antidiabetic drug for objectives 3 and 5, and when discontinuing the specific GLP-1 RA ingredient for objectives 4 and 6.
• Comparators:
  Not applicable
• Outcomes:
  Not applicable
• Summary results:
  Analyses will be completed in each provincial database and will be pooled across provinces where appropriate. We will estimate the monthly incidence and monthly point prevalence of prescriptions of GLP-1 RA with 95% confidence intervals, overall, by ingredient, and selected brands. We will describe new users’ demographics, comorbidities, and other specified covariates. Characteristics will be summarized overall and stratified by ingredient, selected brands, and indication cohorts. We will describe the GLP-1 RA switching of substances and to other antidiabetics among new users of the respective medicine, by calculating the median time-to-switch and average time-on-treatment and provide Kaplan-Meier curves. Treatment trajectories will be represented using Sankey diagrams. Within-substance switching of strength will be similarly reported. Objectives 3 and 5 will be stratified by indication cohorts, and objectives 5 and 6 will be conducted subject to feasibility.