Metformin, a common Type 2 diabetes, may offer protection against a subtype of age-related macular degeneration (AMD), according to a study published in Investigative Ophthalmology & Vision Science (IOVS).

This is the latest among other studies suggesting that the medication may have several uses beyond diabetes, such as promoting longevity and weight loss and protecting against neurological disorders, cancer, and cardiovascular disease. Most of the proposed uses are off-label, which means the U.S. Food and Drug Administration (FDA) has not approved the medication to treat those conditions.

While research on some off-label metformin uses is promising, studies on other uses are inconsistent. Some are controversial because they may not offer the best approach for addressing a health issue. Additionally, although metformin is generally well-tolerated, it does have some adverse effects and is not for everyone.

Metformin and Macular Degeneration Subtype

Macular degeneration, a condition mainly associated with aging, affects the retina and involves the loss of central vision. The primary types of AMD are wet AMD and dry AMD. Geography atrophy (GA) is a subtype of dry AMD. GA leads to legal blindness in 16 percent of those who have it.

In recent years, anti-vascular endothelial growth factor (VEGF) medications, which decrease the growth of blood vessels in the eye, have revolutionized treatment for wet AMD.

Conversely, treatments for GA have lagged. In 2023, pegcetacoplan and avacincaptad pegol came on the market, but they only slow GA’s progression rather than prevent the condition.

Studies on the treatment of dry AMD with metformin have been encouraging, but they have not focused on GA specifically. Because of the limited research on metformin’s effect on GA and the condition’s debilitating visual effects, researchers undertook the IOVS study.

This case-control experiment involved older individuals with new-onset GA and a control group who did not have it. The researchers looked at exposure to metformin in the preceding year to determine whether any correlations were present. Data analysis indicated an association between metformin and reduced risk of new-onset GA. The researchers concluded that further research is necessary to verify the findings, but metformin may provide a noninvasive alternative treatment in preventing GA.

Mechanisms of action underlying the benefit of metformin on GA are unclear, but there are several possibilities. Instead of the protective effects stemming from a blood sugar-lowering action useful for diabetes, the effects may be due to the medication’s anti-inflammatory and antioxidant properties, based on animal and test tube studies.

Metformin and Aging

Is it possible that taking a pill can prolong your life? A review published in Frontiers in Endocrinology noted that metformin may decrease the likelihood of early death associated with diabetes, cancer, cognitive decline, and cardiovascular disease, which could lengthen the period of life spent in good health.

Factors underlying metformin’s anti-aging effects include its ability to lower high blood sugar, boost insulin sensitivity, and decrease oxidative stress. The medication also has a direct protective effect on blood vessel function, which may improve blood flow.

Despite these positive effects, the researchers expressed reservations about using metformin as a prophylactic (preventive) measure to promote longevity. Dependence on a pill could reduce the incentive to adopt healthy lifestyle practices, such as exercise and a nutritious diet, which have proven beneficial. Additionally, long-term metformin use may cause vitamin B12 deficiency. In light of these considerations, people should not view the drug as a “quick fix” for aging.

Dr. Markus Ploesser, a psychiatrist and integrative medicine physician at Open Mind Health, concurs with the researchers’ viewpoint. In an email to The Epoch Times, he stated that metformin has several beneficial effects that may enhance longevity; “however, its use as an anti-aging drug is still not fully proven.”

Ploesser added that it is essential to balance the possible benefits against risks and to consider it within a broader context of other longevity-promoting strategies, such as diet, exercise, sleep optimization, and stress management.

“Taking a pill alone is unlikely to be the healthiest approach for most people, as a comprehensive lifestyle strategy has much stronger evidence for promoting longevity,” he said.

Metformin and Weight Loss

Metformin may promote weight loss, but its use is best reserved for a select population.

A review published in Current Obesity Reports stated that it suppresses the appetite and may also increase the abundance of bacterial strains in the gut microbiome, an effect associated with healthier weight. However, research on the weight-loss effects of metformin shows either modest improvement or inconsistent results. Consequently, the FDA has not approved the medication for obesity.

Guidelines from the American Association of Clinical Endocrinologists and the American College of Endocrinology advise the use of metformin for obese individuals who have prediabetes or insulin intolerance and have not responded to other medications for obesity or lifestyle modifications. Current use of the drug for obesity is strictly off-label, but doctors often prescribe it for people with a high risk of obesity-related complications who can’t tolerate other interventions, noted the Current Obesity Reports review.

Dr. Michael Lahey, a physician specializing in metabolic health and weight management at My Weight Loss Partner, told The Epoch Times via email that although some research shows metformin might promote weight loss, it is not an anti-obesity medication.

“In my experience, I stand to defend the facts that making the necessary lifestyle changes—such as proper dieting, reliable exercise, and positive behavioral change—has the strongest bearing for long-term, effective weight loss,” he said. “It can be suggested that metformin may be used as a second-line treatment, in particular, if insulin resistance is quite pronounced; nonetheless, it should not be used alone.”

Metformin and Neurological Disorders

A review published in the International Journal of Molecular Sciences indicates that metformin may protect against neurological conditions, including Alzheimer’s disease and major depressive disorder.

The mechanisms that underlie the protection are not fully understood, but several actions may play a role. Metformin may help prevent damage to the blood-brain barrier (BBB), a tight layer of cells that prevents harmful substances from entering the brain. Damage to the BBB can result in neuroinflammation and injury, leading to neurodegeneration.

Metformin also moderates autophagy, a natural cleaning process that improves cellular function. It also regulates synaptic transmission, where neurotransmitters are released that send signals from one nerve cell to another, and plasticity, or the ability of neural networks to grow and reorganize.

Metformin and Cardiovascular Protection

A review published in Pharmaceuticals reported that an estimated two-thirds of the deaths of people with diabetes are attributable to cardiovascular disease. Among this group, approximately 40 percent stem from coronary artery disease, 15 percent from heart failure and other types of heart disease, and about 10 percent from stroke. Consequently, reducing the likelihood of these risks is paramount.

Most clinical studies indicate that metformin may decrease the likelihood of chronic blood vessel-related complications of diabetes and significantly lower modifiable cardiovascular risk factors. The latter includes increased platelet aggregation, unhealthy blood lipids, belly fat, obesity, oxidative stress, high blood glucose, and inflammation.

Metformin and Kidney Protection

According to the Pharmaceuticals review, chronic kidney disease affects about 30 percent of people with Type 1 diabetes and approximately 40 percent of those with Type 2 diabetes. This result of chronically high blood sugar affects tiny blood vessels and frequently leads to end-stage kidney disease. Existing medications are ineffective, and many people eventually need dialysis or a kidney transplant.

Metformin has kidney-protective properties that can stop kidney tissue injuries caused by various toxins, including high blood glucose.

This benefit’s underlying mechanisms of action are complex and not fully known. A factor that plays a key role is metformin’s activation of the enzyme AMP-activated protein kinase (AMPK), which results in beneficial effects in kidney cells. AMPK serves as a vital energy source in the cell and regulates cellular protein, glucose, and lipid metabolism.

Metformin and Cancer

People with diabetes, particularly Type 2 diabetes, have a higher risk of developing certain cancers, including breast, bladder, endometrium, pancreas, liver, and colon and rectum, noted the review in Pharmaceuticals. Metformin has a desirable effect on certain cancer risk factors, such as high body weight, high blood sugar, and insulin sensitivity.

Research shows the medication reduces the risk of cancer in people with diabetes, but exactly how it achieves this protective effect is only partly understood. One factor involves an indirect action on tumor cells caused by the blood sugar- and insulin-lowering effects, which may suppress cancer cell proliferation. Additionally, researchers have proposed that metformin has several direct anti-cancer effects, such as the activation of AMPK in tumor cells.

While some studies suggest the medication may reduce the risk of cancer, others do not. The inconsistency shows that randomized studies are needed to determine the value of metformin in cancer.

Safety Concerns

Metformin is generally well-tolerated, but up to 30 percent of people experience gastrointestinal effects, such as nausea, diarrhea, and vomiting.

Australian physician and board-certified nutritionist Dr. Peter Brukner told The Epoch Times via email that people with the following conditions or risk factors should avoid metformin:

• Kidney problems: The kidneys remove metformin from the body, so the medication is not eliminated properly if they are not working well. This can cause lactic acidosis, a complication where the blood pH drops and becomes acidic, causing severe illness.
• Liver problems: The liver also has a job in handling metformin. Liver disease puts a person at risk of lactic acidosis.
• Breathing problems or heart issues: A person with severe breathing problems or heart issues might not get enough oxygen. This, too, can make them more likely to develop lactic acidosis.
• History of lactose acidosis: If someone has experienced lactic acidosis before, it is a good idea not to take metformin because the problem may come back.
• Pregnant or breastfeeding women: Metformin is not always suggested for women who are pregnant or breastfeeding since its impact on the baby is not entirely known. Doctors often seek safer choices in such situations.
• Certain medications: Some medications do not go well with metformin and can create problems. These include those that raise the risk of lactic acidosis, such as bupropion, carbonic anhydrase inhibitors, and cephalexin and medications that enhance its blood sugar-lowering effect, such as salicylates and selective serotonin reuptake inhibitors (SSRIs). Individuals should inform their doctor about all the medications they use to avoid drug interactions.

Anyone desiring to take metformin with one of these conditions should discuss it with their doctor, Brukner advises.

Risk Versus Benefit

While further research is needed, metformin’s uses for disease prevention may be valid. However, doctors must weigh the benefits against the risks for each individual. In cases where a person is highly likely to develop a particular condition, the benefits may exceed the risks.