A FitEyes member shared the following article:

Study Links Metformin to Lower Glaucoma Risk in Nationwide Cohort

For any of us already on Metformin, this is encouraging. However, for those not already on Metformin and who may be considering it for glaucoma, below is a critical review of this study (and it suggests some reasons to be skeptical).

Metformin's History

Metformin (dimethylbiguanide) has become the preferred first-line oral blood glucose-lowering agent to manage type 2 diabetes.

Metformin's history is linked to the herb Galega officinalis (also known as goat's rue), a traditional herbal medicine in Europe, found to be rich in guanidine, which, in 1918, was shown to lower blood glucose. This led to the synthesis of guanidine derivatives, including metformin.

Metformin works by reducing the amount of sugar your liver produces and helping your body respond better to insulin.

Sadly, a 2023 systematic review searching for human clinical trials on Galega officinalis found almost no human research and no randomized clinical trials. All the research has focused on the pharmaceutical derivatives. Consequently, there is no comprehensive modern documentation of side effects for Galega officinalis in humans. This absence likely reflects the plant's relatively limited commercial prospects. However, Galega officinalis is a recognized toxic plant in veterinary medicine, causing fatal poisonings in sheep and cattle grazing on the plant, and this does raise valid concerns for human use of Galega officinalis.

Metformin, on the other hand, has been used safely for decades and is often the first medication prescribed for type 2 diabetes.[[1]]

Is There a Connection Between Metformin and Glaucoma?

Recent research has explored whether metformin might help protect against glaucoma. Several large studies have found that people with diabetes who take metformin appear to develop glaucoma less often than those who don't take metformin.[[2]][[3]]

This study, using data from over 18,000 participants in the National Institutes of Health All of Us Research Program, found that metformin users had a significantly lower rate of developing glaucoma compared to non-users. This study was notable for including a diverse population, with substantial representation of Black/African American and Hispanic/Latino participants—groups that are disproportionately affected by glaucoma.

Important Limitations: Why We Can't Be Certain

While these findings are interesting, we cannot conclude that metformin actually prevents glaucoma. Here's why:

The "healthy user" effect: People who take metformin tend to be healthier overall than people with diabetes who take other medications. This is because metformin is typically prescribed to patients with less severe diabetes and better kidney function. Sicker patients often need to switch to insulin or other medications. This means metformin users may have lower rates of many diseases -- not because of metformin itself, but because they are healthier to begin with.[[4]]

Research has shown that when scientists look at conditions that metformin cannot possibly affect (like hernias or bone fractures), metformin users still appear to have lower rates of these conditions. This tells us that the apparent "benefits" of metformin in observational studies may actually reflect the overall better health of people who take it, rather than a true protective effect of the drug.[[4]]

These studies cannot prove cause and effect: All of the current research on metformin and glaucoma comes from observational studies, which can only show associations, not that one thing causes another. To truly know if metformin prevents glaucoma, we would need randomized controlled trials where some patients are randomly assigned to take metformin and others are not.

What Does This Mean for You?

Glaucoma researchers say you should not start or stop metformin based on glaucoma concerns. Metformin should be taken as prescribed by your doctor for diabetes management. There is not enough evidence yet to recommend metformin specifically for glaucoma prevention.

Proven Ways to Protect Your Eye Health

While the evidence for metformin and glaucoma remains uncertain, there are lifestyle factors that may support eye health:[[1]]

• Regular exercise: Moderate aerobic exercise (like walking, swimming, or cycling) has been associated with lower glaucoma risk

• Healthy diet: Eating green leafy vegetables and maintaining a balanced diet may be beneficial. See other articles on Ask FitEyes and https://www.reddit.com/r/AskGlaucoma/ for more information.

• Neuroprotective dietary supplements: Research is accumulating that certain dietary supplements are protective against glaucoma. See other articles on Ask FitEyes and https://www.reddit.com/r/AskGlaucoma/ for more information.

• Avoid smoking: Smoking is associated with worse outcomes for many eye conditions

• Limit alcohol: Heavy alcohol consumption may increase glaucoma risk

• Maintain a healthy weight: Obesity has been linked to higher glaucoma risk

• Get regular eye exams: Early detection is crucial since glaucoma often has no symptoms until vision loss occurs

Ongoing Research

Scientists are currently conducting clinical trials to determine whether metformin truly has protective effects on the eyes. These trials will provide much stronger evidence than the observational studies we have today. Until those results are available, the connection between metformin and glaucoma remains an interesting possibility that requires further investigation.

Ongoing Trials for Cognitive/Dementia Outcomes

Several randomized trials are currently investigating metformin for dementia prevention in normoglycemic populations (since it would be unethical to randomize diabetic patients to placebo):

• MetMemory: A 3-year intervention in insulin-resistant normoglycemic participants with mild cognitive impairment

• Metformin in Alzheimer's Prevention: Testing metformin in participants with Alzheimer's disease

• MET-FINGER: A multimodal trial combining metformin with intensive lifestyle intervention

Ongoing Trials for Glaucoma

The Sidhu et al. scientific paper references two registered clinical trials specifically examining metformin for glaucoma neuroprotection:

• NCT04155164 (Zhongshan Ophthalmic Center): Examining metformin's effect on visual function in patients with primary open-angle glaucoma

• NCT04155177 (Christopher P.): Testing metformin as a neuroprotective therapy for glaucoma

References

1. [Association of Diabetes Medication With Open-Angle Glaucoma, Age-Related Macular Degeneration, and Cataract in the Rotterdam Study]. Vergroesen JE, Thee EF, Ahmadizar F, et al. JAMA Ophthalmology. 2022;140(7):674-681. doi:10.1001/jamaophthalmol.2022.1435.
2. [Association of Geroprotective Effects of Metformin and Risk of Open-Angle Glaucoma in Persons With Diabetes Mellitus]. Lin HC, Stein JD, Nan B, et al. JAMA Ophthalmology. 2015;133(8):915-23. doi:10.1001/jamaophthalmol.2015.1440.
3. [Association of Metformin Use Among Diabetics and the Incidence of Primary Open-Angle Glaucoma - The Chennai Eye Disease Incidence Study]. George R, Asokan R, Vijaya L. Indian Journal of Ophthalmology. 2021;69(11):3336-3338. doi:10.4103/ijo.IJO_1486_21.
4. [Comparative Effects of Glucagon-Like Peptide 1 Receptor Agonists and Metformin on Glaucoma Risk in Patients With Type 2 Diabetes]. Muayad J, Loya A, Hussain ZS, et al. Ophthalmology. 2025;132(3):271-279. doi:10.1016/j.ophtha.2024.08.023.
5. [Comparative Risk of Glaucoma in Patients Using Sodium-Glucose Cotransporter-2 Inhibitors and Metformin: A Multinational Cohort Study]. Pan SY, Weng CH, Tsai SF, et al. American Journal of Ophthalmology. 2025;:S0002-9394(25)00504-5. doi:10.1016/j.ajo.2025.09.027.