A study recently published in Ophthalmology Retina evaluated the association between metformin use and the risk of age-related macular degeneration (AMD) development among diabetic patients.
Give me some background.
Metformin is a commonly prescribed oral diabetes medication that has been shown to have a potential protective effect on AMD due to its anti-angiogenic, anti-inflammatory, and neuroprotective effects on the retina.
In fact: A recent meta-analysis found a significant association between oral metformin use and reduced odds of AMD in diabetic patients.
Though: The study’s authors explained that this association is less researched in nondiabetic patients, and requires randomized clinical trials (RCTs) to determine the effectiveness of metformin for preventing the onset of AMD.
Bring it back to this study.
A key mediator in the association between metformin use and AMD risk is likely the duration of treatment due to the gradual progression of AMD.
- As such: A research team sought to bridge this gap in knowledge by studying a large cohort of diabetic patients with a specific focus on duration of metformin exposure.
Now let’s get into it.
In this retrospective cohort study, investigators utilized the TriNetX platform to identify patients using International Classification of Diseases, Tenth Revision (ICD-10) and Current Procedural Terminology (CPT) codes for diabetes and ophthalmic care.
- The main exposure: Annual metformin use for ≥5 years, with subanalysis up to 10 years
Primary outcome measure: New diagnosis of AMD
- Secondary outcomes: A new diagnosis of dry and wet AMD
What about the cohort?
Patients aged ≥60 years with diabetes and no documentation of AMD were included in the analysis.
- Specifically: Patients were required to have no AMD diagnoses at two eye care visits ≥1 year apart, with the second visit serving as the index event for analysis.
Propensity score matching (PSM) controlled for potential confounders, including:
- Demographics
- Comorbidities
- Medications
- Laboratory values
- Health care utilization
Findings?
After PSM, the main cohort analysis included 7,496 patients, of whom 3,748 had ≥5 consecutive years of metformin use.
Incident AMD was documented in 122 (3.3%) patients who had been exposed to metformin and 184 (4.9%) who had not (hazard ratio [HR]: 0.68, 95% confidence interval [CI]: 0.54-0.85).
In sensitivity analyses comparing insulin as a negative control and statins as a positive control, insulin usage did not correlate with AMD development, while statins did reflect a protective effect against AMD risk.
Anything else?
Metformin use for ≥6 consecutive years showed consistent protective effects, while 1-4 years showed weaker associations.
Finally: The metformin group had lower rates of both dry AMD (HR: 0.69, 95% CI: 0.53-0.90) and wet AMD (HR: 0.84, 95% CI: 0.50-1.39)—although the association with wet AMD was not statistically significant.
Expert opinion?
These results indicate that “metformin does not significantly slow the progression of existing geographic atrophy, reinforcing the idea that its protective effects may be most relevant in earlier stages of disease development,” the study authors explained.
Any limitations?
One major factor: The analyses in this study were performed in a series of nested cohorts with varying durations of preceding data.
- Meaning: “Patterns observed between the cohorts with longer and shorter durations of metformin are not independent and should be interpreted with caution,” according to the authors.
Take home.
These findings demonstrate that prolonged metformin use in diabetic patients was associated with a reduction in AMD risk.
In other words: Metformin may have a protective effect against AMD, warranting further exploration with RCTs to elucidate its long-term effects on AMD prevention.