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 identification

• EU PAS number:
  EUPAS1000000966
• Study ID:
  1000000966
• Official title and acronym:
  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
• DARWIN EU® study:
  No
• Study countries:
  United States
• Study description:
  This study aims to estimate the comparative effect of initiating a GLP-1RA versus alternative second-line glucose-lowering therapies—sodium–glucose cotransporter-2 inhibitors (SGLT-2i) and dipeptidyl peptidase-4 inhibitors (DPP-4i)—on the risk of incident NAION among older adults with type 2 diabetes. We will conduct two parallel active-comparator, new-user cohort studies emulating separate head-to-head target trials. New use will be defined by a 12-month class-specific washout, and eligibility, exposure assignment, and follow-up will be aligned at the first prescription fill to avoid immortal time and ensure proper temporality. Follow-up will proceed under an as-treated framework until treatment discontinuation, switching, outcome occurrence, death, disenrollment, or end of data.; ; The study will use a 20% random sample of Medicare Fee-for-Service Parts A, B, and D claims, providing large-scale, nationally representative data suitable for evaluating the rare outcome of NAION in older adults. Analyses will estimate absolute and relative risks using standardized morbidity ratio (SMR) weighting to target the average treatment effect in the treated. SMR-weighted Aalen–Johansen cumulative incidence functions will provide adjusted risks accounting for competing mortality, complemented by SMR-weighted Cox models for hazard ratios. Secondary analyses will evaluate as-treated effects conditional on a second refill of the same drug class within days’ supply of the index prescription plus a grace period of 30 days, as well as intention-to-treat effects. Finally, sensitivity analyses will address outcome definitions, induction and latency windows, grace-period choices, propensity-score overlap, and unmeasured confounding.
• Study status:
  Ongoing

Research institutions and networks

Institutions

University of North Carolina at Chapel Hill

Study timelines

Date when funding contract was signed

Planned:25/02/2026

Actual:25/03/2026

Study start date

Planned:25/03/2026

Actual:25/03/2026

Data analysis start date

Planned:25/03/2026

Actual:25/03/2026

Date of final study report

Planned:24/09/2027

Sources of funding

No external funding

Regulatory

• Was the study required by a regulatory body?:
  No
• Is the study required by a Risk Management Plan (RMP)?:
  Not applicable