Metformin No Help Against AMD, New Study Finds

No significant association between metformin and the risk of age-related macular degeneration was observed in this study. Even after viewing data at five and 10 years, the risk remained the same between patients who were prescribed the drug and those who were not. Photo: NEI. Click image to enlarge. Prescription drugs are carefully formulated to treat specific diseases and conditions; however, unanticipated effects (both good and bad) are often identified “in the wild” and some drugs then undergo further testing to explore other indications of use. Several diabetes medications have demonstrated positive as well as negative effects in recent years and have proven a fruitful area for research. In a new JAMA Ophthalmology paper, researchers observed the use of anti-diabetic drug metformin and its potential effects to protect against the development and progression of age-related macular degeneration (AMD).1Using the TriNetX database, researchers gathered electronic health record (EHR) information from 70 institutions to answer whether or not metformin is associated with the development and progression of AMD. Subjects who met the inclusion criteria were divided into two cohorts. The first included subjects with no diagnosis of AMD, and the second included subjects with a diagnosis. AMD was identified using ICD codes in the records.Observations revealed no significant association between metformin and the development and progression of AMD. A cohort with no history of AMD comprised 297,008 individuals prescribed metformin and 1,269,644 individuals without a history of metformin use. A second cohort, this time of AMD patients, was much smaller in population, enlisting 12,843 individuals prescribed metformin and 77,279 individuals without a history of use. When the researchers employed propensity score matching, they discovered that the risk of developing AMD was comparable between participants prescribed and those without a prescription of metformin (relative risk: 0.90). Furthermore, similar results for the risk of progression to neovascular or geographic atrophy were observed between the two groups.“Further studies and prospective analyses are necessary to better evaluate whether dosage and longevity of metformin use may influence AMD development or progression,” concluded the authors in the paper. There were multiple limitations that led to this notion. For instance, metformin is typically prescribed to type 2 diabetes patients, and other prescription drugs were not taken into account for this study. Additionally, the assessment of metformin use was limited by the data, and adherence to the drug could not be examined. Other data points such as quantity, frequency and longevity of the prescriptions were not available either. Lastly, EHR data is not perfect, and ICD could have been misclassified, leading to limited results.An invited commentary also published in JAMA Ophthalmology noted additional shortcomings to this study.2 They addressed the fact that EHR data can present significant challenges when analyzing the potential advantages and disadvantages of metformin. When selecting participating data for their study, researchers excluded individuals without ICD codes for AMD. The commentary authors stated that this does not definitively entail the absence of this ocular condition, since subjects may be experiencing AMD without a diagnosis.Another flaw pointed out by the commentators was the unavoidable inclusion of the differential measurements of outcomes. They explained that patients prescribed metformin typically undergo regular screening for diabetic retinopathy, while others most likely do not receive such care and observation; therefore, conditions such as AMD can go overlooked. One suggestion for future researchers is to conduct studies with a target trial emulation framework. While this model uses observational data similar to the propensity score matching model seen in the aforementioned study, target trial emulation’s design takes the data and mimics a randomized clinical trial. This, the commentators believe, could help mitigate biases seen in traditional analyses.The commentary did highlight some positive outcomes from this study. It recognized the study authors’ “careful interpretation of findings and for clearly acknowledging the many limitations of their analysis.” Outcomes were noted as a valuable reminder of what can be expected when conducting a study using data to explore how drugs can be repurposed for other opportunities.“Until high-quality causal evidence is available, the totality of the currently available evidence does not support the consideration of clinicians to prescribe metformin for the sole purpose of preventing AMD or slowing its progression,” the commentary authors concluded. Click here for the journal source and here for the commentary. 1. Jindal DA, Hanna J, Shaia JK, et al. Metformin and the development of age-related macular degeneration. JAMA Ophthalmol. September 18, 2025. [Epub ahead of print].2. Liu SH, Mandava N, Li T. Metformin and age-related macular degeneration—no causal evidence yet. JAMA Ophthalmol. September 18, 2025. [Epub ahead of print]. This article was developed by the editorial staff in conjunction with experts in the field. In the process, AI may have been among the editorial tools used to meet the goals of human editors, who approved all content.