Influence of Common Medications on Diabetic Macular Edema in Type 2 Diabetes Mellitus

Purpose: This study aimed to assess the impact of systemic medications, including GLP-1 receptor agonists (GLP-1 RAs), fenofibrates, thiazolidinediones (TZDs), and calcium channel blockers (CCBs), on the risk of developing diabetic macular edema (DME) in patients with type 2 diabetes mellitus (T2DM).

Design: A retrospective cohort study was conducted using electronic medical records (EMR) data from the TriNetX health research network, covering a period from October 2004-2024.

Participants: The study population comprised patients diagnosed with T2DM who were newly initiated on GLP-1 RAs, fenofibrates, TZDs, or CCBs. Propensity score-matched (PSM) controls were T2DM patients who did not receive these medications within the same timeframe.

Methods: Patients were observed for one to two years post-medication initiation to monitor the development of DME. The study utilized 1:1 propensity score matching to adjust for baseline characteristics and comorbidities.

Main outcome measures: The primary outcome measure was the incidence rate of DME within the two-year follow-up period. Hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated to compare the risk of DME between treatment and control groups.

Results: Post-PSM, the study analyzed data from 107,193 patients in the CCB cohort, 76,583 in the GLP-1 agonists cohort, 25,657 in the thiazolidinediones cohort, and 18,606 in the fenofibrates cohort. CCB-treated patients demonstrated a higher risk of DME development compared to controls (HR: 1.66, 95% CI: 1.54-1.78). In contrast, GLP-1 RA-treated patients showed a decreased risk of DME (HR: 0.77, 95% CI: 0.70-0.85), as did fenofibrate-treated patients (HR: 0.83, 95% CI: 0.68-0.98). No significant difference in DME risk was observed in the thiazolidinediones cohort (HR: 1.08, 95% CI: 0.94-1.25).

Conclusions: Patients on GLP-1 RAs and fenofibrates experienced a lower risk of DME diagnosis, suggesting a protective effect against DME development in patients with T2DM, while those on CCBs experienced an increased risk. These findings suggest that systemic medications may significantly influence DME outcomes, warranting further investigation into their effects on retinal health.