Effect of Glucagon-Like Peptide-1 Receptor Agonists on the Risk of Non-Arteritic Anterior Ischemic Optic Neuropathy Among Older Adults with Type 2 Diabetes: A US. Medicare Active-Comparator New-User Cohort Study

Study type

• Study topic:
  Disease /health condition

  Human medicinal product
• Study type:
  Non-interventional study
• Scope of the study:
  Safety study (incl. comparative)
• Data collection methods:
  Secondary use of data

Non-interventional study

• Non-interventional study design:
  Cohort

Study drug and medical condition

• Medicinal product name:
  OZEMPIC

  RYBELSUS

  WEGOVY

  VICTOZA

  SAXENDA

  TRULICITY

  MOUNJARO

  JARDIANCE

  INVOKANA

  STEGLATRO

  JANUVIA
• Medicinal product name, other:
  FARXIGA; NESINA; TRADJENTA; SAXAGLIPTIN
• Study drug International non-proprietary name (INN) or common name:
  EXENATIDE

  LIRAGLUTIDE

  LIXISENATIDE

  ALBIGLUTIDE

  DULAGLUTIDE

  SEMAGLUTIDE

  DAPAGLIFLOZIN

  CANAGLIFLOZIN

  EMPAGLIFLOZIN

  ERTUGLIFLOZIN

  ALOGLIPTIN

  LINAGLIPTIN

  SAXAGLIPTIN

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

  exenatide

  (A10BJ02) liraglutide

  liraglutide

  (A10BJ03) lixisenatide

  lixisenatide

  (A10BJ04) albiglutide

  albiglutide

  (A10BJ05) dulaglutide

  dulaglutide

  (A10BJ06) semaglutide

  semaglutide

  (A10BK01) dapagliflozin

  dapagliflozin

  (A10BK02) canagliflozin

  canagliflozin

  (A10BK03) empagliflozin

  empagliflozin

  (A10BK04) ertugliflozin

  ertugliflozin

  (A10BH01) sitagliptin

  sitagliptin

  (A10BH03) saxagliptin

  saxagliptin

  (A10BH04) alogliptin

  alogliptin

  (A10BH05) linagliptin

  linagliptin
• Medical condition to be studied:
  Optic neuropathy
• Additional medical condition(s):
  Non-Arteritic Anterior Ischemic Optic Neuropathy

Population studied

• Short description of the study population:
  Fee-for-service Medicare beneficiaries age 66 or above with type 2 diabetes initiating either GLP1-RA, SGLT2i, or DPP4i after a 12 months washout period without any dispensed prescriptions for any of the drug classes and continuous Parts A, B, D enrollment, at least one claim with a type 2 diabetes code, and at least one ophthalmology or optometry encounter during the 12 months prior to drug initiation. ; Exclusions: ; • Diabetes mellitus other than type 2 diabetes; • Same-day initiation of both study drug classes; • GLP-1RA contraindications including pancreatitis, thyroid cancer, multiple endocrine neoplasia type 2, end-stage renal disease, dialysis dependence or renal replacement therapy; • Heart failure for GLP-1RA vs. DPP-4i cohort; • Bilateral blindness or legal blindness; • Prior ischemic optic neuropathy; • NAION mimickers (non-ischemic optic neuropathies; • Prior arteritic/systemic vasculitic conditions; • Empiric evaluation or treatment for suspected arteritic anterior ION
• Age groups:
  • Elderly (≥ 65 years)

    • Adults (65 to < 75 years)
    • Adults (75 to < 85 years)
    • Adults (85 years and over)

Study design details

• Study design:
  Active comparator new user cohort study
• Main study objective:
  To estimate the comparative effect of initiating GLP-1RA versus other second-line glucose-lowering therapies—specifically dipeptidyl peptidase-4 inhibitors (DPP-4i) and sodium-glucose co-transporter-2 inhibitors (SGLT-2i)—on the risk of non-arteritic anterior ischemic optic neuropathy (NAION) among older adults with T2DM.
• Setting:
  US fee-for-service Medicare population
• Comparators:
  GLP1-RA, SGLT2i, DPP4i
• Outcomes:
  First incident non-arteritic anterior ischemic optic neuropathy (NAION)
• Data analysis plan:
  We will define exposure duration using pharmacy dispensing dates and days’ supply. Continuous exposure is defined as sequential fills with ≤30-day allowable gaps (i.e., refill within days supply + 30 days grace period). Exposure episodes end on the earliest of treatment discontinuation, switching to the comparator class, initiation of the alternate study drug class, disenrollment, death, or end of data. For as-treated analyses, risk time is attributed to the observed exposure episode; for intention-to-treat analyses, exposure is fixed at cohort entry. NAION follow-up begins after a 14-day induction lag period and ends 14 days after discontinuation or switching/augmenting (latent period).; Propensity scores will be used for weighting the comparator cohorts (SGLT2i and DPP4i, respectively) to the GLP-1RA cohort to estimate tha average treatment effect in the treated (ATT).