A recent study published in Ophthalmology Retina evaluated the impact of common systemic medications on the risk of developing diabetic macular edema (DME) in patients with type 2 diabetes mellitus (T2DM).
Give me some background.
The rising burden of T2DM is a growing concern for healthcare providers globally, with the number of young (< 20 years) diabetic patients in the United States likely to substantially increase in future decades—emphasizing the need for prevention to mitigate this trend.
More recently: A new addition to the therapeutic armamentarium for diabetes is semaglutide, a glucagon-like peptide-1 receptor agonist (GLP-1 RA), which has seen a 40-fold increase in its use over the past 5 years.
- As such: Researchers have been interested in elucidating the impact of semaglutide (and other systemic medications for diabetes management) on the risk of diabetic eye disease.
Now, talk about the study.
In this retrospective cohort study, investigators analyzed the impact of initiating common systemic medications (listed below) on the risk of developing DME in T2DM patients:
- GLP-1 RA
- Fenofibrate
- Thiazolidinedione (TZD)
- Calcium channel blocker (CCB)
Electronic medical records (EMR) data from the TriNetX health research network covering a period from October 2004 to 2024 was used for this analysis.
- To note: TriNetX is a global federated health research network with deidentified EMRs from 131 healthcare organizations across 17 countries.
Primary outcome measure: The incidence rate of DME within a 2-year follow-up period.
Give me more details on the study population.
The research team used 1:1 propensity score matching (PSM) to adjust for baseline characteristics and comorbidities.
After PSM, the study analyzed EMR data from:
- CCB cohort: 107,193 patients
- GLP-1 RA cohort: 76,583 patients
- TZD cohort: 25,657
- Fenofibrate cohort: 18,606
And the findings?
CCB-treated patients demonstrated a higher risk of DME development compared to controls (hazards ratio [HR] 1.66, 95% confidence interval [CI] 1.54-1.78).
Conversely, 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).
- Notably: No significant difference in DME risk was observed in the TZD cohort (HR 1.08, 95% CI 0.94-1.25).
Expert opinion?
The study authors commented on the potential mechanism of action behind the associations seen between some of the drugs on DME risk, including:
- GLP-1 RAs: A previous study suggested semaglutide had beneficial effects on endothelial cells and antioxidant pathways—with differential regulation of T cells and interferon-gamma.
- CCBs: Prior research has demonstrated increased peripheral extremity edema in patients taking CCBs, which may share vascular regulatory pathways with DME.
- Further, CCBs may increase vascular endothelial growth factor (VEGF) concentrations in retinal cells.
Tie it all together for me.
These findings suggest that patients on GLP-1 RAs and fenofibrates experienced a lower risk of DME diagnosis.
- What this may mean: A potential protective effect against DME development in patients with T2DM.
On the other hand, patients on CCBs experienced an increased risk of DME, and those on TZDs had no significant difference in risk.
Next steps?
The study authors noted that further research is required to clarify the mechanisms behind these associations and determine if the observed effects were due to the direct pharmacological impact of the drugs or the improved systemic control achieved by their use.
“Enhanced systemic management may prove less burdensome and more cost effective than high-frequency intravitreal anti-VEGF therapy while also reducing non-ocular morbidity and mortality,” they added.