The Miracle of Metformin Against Diabetes, Cancer, COVID-19 and Dementia

One of the cheapest and most effective medicines for controlling blood sugar has been around for decades. In truth, though, herbalists were using goat’s rue (French lilac) for hundreds of years before scientists discovered metformin. These days this drug is the most prescribed diabetes medicine in the world. But the benefits may extend beyond blood sugar control. The miracle of metformin may also be in its anti-cancer activity. In addition, people infected with COVID-19 are far less likely to suffer long COVID if they are taking metformin. A recent study also found that metformin can reduce the chance of developing cognitive decline.

The Miracle of Metformin Against Dementia:

A study published in JAMA Network Open found that people with type 2 diabetes were more likely to develop dementia if they stopped taking their metformin (JAMA Network Open, Oct. 25, 2023). Researchers analyzed data from electronic health records at Kaiser Permanente. More than 12,000 individuals discontinued metformin. The investigators matched them with over 29,000 people who continued taking their anti-diabetic drug metformin. Those who dropped the drug were 21% more likely to be diagnosed with dementia during the subsequent five years. On the other hand, neither HbA1c nor insulin use was linked to this increased risk. Scientists suggest, therefore, that metformin may be protective against dementia.

Metformin Reduced Risk for Long COVID:

A preliminary study posted as a preprint on The Lancet compared ivermectin, fluvoxamine and metformin in the treatment of COVID-19 (March 6, 2023). More than 1,100 patients participated. All were overweight or obese, and thus at risk for serious COVID-19 complications. The researchers randomly assigned them to one of these three drugs or to placebo within three days of a confirmed COVID diagnosis.

Patients taking the diabetes drug metformin for two weeks during their illness were 42% less likely to be diagnosed with long COVID over the following 10 months. This is, of course, a relative risk reduction. In the group taking metformin, 6.3% developed long COVID compared to 10.6% on placebo for metformin. Statistics for the other drugs were lackluster. 8.0% of those taking ivermectin came down with long COVID, compared to 8.1% on the ivermectin placebo. The numbers were 10.1% for fluvoxamine and 7.5% for fluvoxamine placebo. Thus, neither of the other drugs reduced the likelihood of long COVID.

The Latest Metformin Success Against Long COVID:

First, we must acknowledge a modest conflict of interest. One of the authors of this research is Dr. John Buse. He is an endocrinologist at the University of North Carolina, Chapel Hill. He has been a frequent guest on The People’s Pharmacy syndicated radio show and we consider him a friend. He is one of 31 authors on this paper.

Second, y0u have got to read the title of this important study:

“Outpatient Treatment of COVID-19 and the Development of Long COVID Over 10 Months:

A Multi-Center, Quadruple-Blind, Parallel Group Randomized Phase 3 Trial”

Sounds impressive, don’t you think? Let’s cut to the chase:

“COVID-OUT was an investigator-initiated, multi-site, phase 3, randomized, quadruple blinded, placebo-controlled clinical trial of outpatient treatment of Covid-19 that followed participants for 10 months to assess whether early treatment prevented the development of Long Covid. Treatment with metformin during acute Covid-19 infection prevented over 40% of Long Covid cases, with 6.3% of participants in the metformin group and 10.6% in the placebo group receiving a diagnosis of Long Covid from a medical provider. Metform preventing over 40% of cases of Long Covid is consistent with the results for the acute Covid outcomes of the trial, in which metformin prevented over 40% of emergency department visits, hospitalizations, and death due to Covid (OR 0.58, 95% CI 0.35 to 0.94) by Day 14. By Day 28, those in the metformin group were also less likely to be hospitalized, 1.34% (8/596) versus 3.16% (19/601) of those receiving placebo.”

You may not view these results as impressive. We would beg t0 differ. To date, there has been no proven treatment to prevent l0ng COVID. To truly prevent this devastating condition, you have to avoid catching the SARS-CoV-2 virus.

Metformin is the first medication to demonstrate effectiveness in a very well controlled trial. Dr. Eric Topol, a researcher whom we have also interviewed numerous times on the radio, calls this drug a “breakthrough” given the clear benefit, low cost ($1-$2 dollars) and safety record. Metformin does have side effects, but the length of treatment is only two weeks, which reduces the overall likelihood of problems.

Metformin vs. Prostate Cancer?

A reader wants to know if there are any data supporting the idea of metformin against prostate cancer:

Q. My doctor recently suggested that I should start taking metformin to help prevent a recurrence of prostate cancer. When I looked the drug up online I discovered that it is prescribed for diabetes. My blood sugar is fine. Why would this drug work against cancer? Won’t my blood sugar drop too low and get me into trouble with hypoglycemia? What other side effects should I know about?

Metformin for Prostate Cancer:

A. One of the most successful diabetes drugs ever discovered originated from folk medicine. French lilac (Galega officinalis), also known as Italian fitch, goat’s rue or professor-weed, had been used for centuries by native healers to help control elevated blood sugar. French researchers found in the 1920s that the active compound could lower blood sugar in an animal model (rabbits).

It took until the 1950s to verify that the miracle of metformin was in the control of diabetes in humans. The FDA approved metformin for sale in the United States in 1994 under the name Glucophage (glucose eater in French). The drug works by enhancing our cells’ response to insulin, thereby improving blood sugar control. Because it is available generically it is inexpensive, making it one of the best deals in diabetes management.

In direct response to your question, metformin is less likely to cause low blood sugar (hypoglycemia) in people with type 2 diabetes than many other drugs. Symptoms to be alert for, though, include dizziness, shakiness, cognitive dysfunction, confusion, headaches, fast pulse, pale skin and hunger. Although hypoglycemia is an unlikely complication, you may want to ask your doctor whether it would be helpful to monitor your blood sugar levels to make sure that they don’t drop too low.

The Miracle of Metformin: Its Anti-Cancer Activity

Evidence continues to mount that metformin may help prevent a number of cancers from developing or if they do, from spreading throughout the body. Here is just a partial list of cancers that may be inhibited by metformin:

• Colorectal Cancer
• Liver Cancer
• Lung Cancer
• Pancreatic Cancer
• Prostate Cancer

Metformin and Prostate Cancer:

Here is a quick summary of some fascinating prostate cancer research: A study of Canadian men with diabetes and prostate cancer suggested that those taking metformin were less likely to die of this malignancy than men taking other diabetes drugs. The study lasted nearly five years. [Journal of Clinical Oncology, online August 5, 2013]

A study of men in Taiwan found that those with diabetes who were treated with metformin had a decreased risk of developing prostate cancer [European Journal of Cancer, online, Sept. 5, 2014]

Another study found that prostate cancer cells may be less likely to progress and metastasize if metformin is on board. [Biochemical and Biophysical Research Communications, online, Sept 6, 2014]

Preventing Prostate Cancer?

A large study from Hong Kong offers some interesting insights into prostate cancer prevention. The study was published in the Journal of the National Comprehensive Cancer Network (June, 2022). The authors analyzed data from men with type 2 diabetes between January 1, 2000 through December 31, 2009. 25,695 men received metformin to control their blood sugar while 25,695 received a different kind of diabetes drug: sulfonylurea.

The results:

“Conclusions: Metformin use was associated with significantly lower risks of new-onset prostate cancer and all-cause mortality than sulfonylurea use in male patients with T2DM.”

The Miracle of Metformin: Preventing Prostate Cancer Recurrence?

The authors also note:

“Research is underway to explore the role of metformin in the treatment of prostate cancer. ADT [androgen deprivation therapy] is the first-line treatment of prostate cancer, but many patients eventually do not respond well and develop castrate resistance. Metformin, when combined with ADT, is associated with improved survival in advanced prostate cancer. In addition, ADT can cause metabolic and cardiovascular consequences, and metformin is shown to ameliorate these adverse effects. Metformin may also be used as an adjuvant to chemotherapy because it reduces the dose necessary to prolong remission. As an adjuvant agent to radical radiotherapy, metformin may improve survival outcomes.”

Metformin and Breast Cancer:

Although metformin seems to have potential benefits against prostate cancer, the same may not be true for breast cancer. This reader wants to know if she should consider metformin even if she does not have diabetes:

Q. Should women take metformin to prevent breast cancer even if they are not diabetic? I have read that this diabetes drug might have anti-cancer benefits.

A. We wish there were a straightforward answer to your thoughtful question. A review of metformin to prevent breast cancer reveals a range of results (International Journal of Molecular Sciences, March, 2022).  In some studies, metformin appeared to help, especially against estrogen-receptor positive tumors. In other studies, however, this insulin-sensitizing drug had no preventive impact.

For treating breast cancer, women with diabetes who take metformin seem to do better. A new randomized controlled trial recruited 3,649 women with breast cancer but no diabetes (JAMA, May 24/31, 2022).

The eight-year follow-up results were disappointing. Women who took metformin were no more likely to avoid cancer complications than those taking placebo. Unless research uncovers more positive results, there is no miracle of metformin for women without diabetes.

There are side effects to be aware of. Do pay attention to some potential complications.

Metformin Side Effects

• Digestive distress including stomach upset, gas, nausea, indigestion, diarrhea
• Loss of appetite
• Headache
• Weakness
• Rash
• Low levels of vitamin B12 (patients may need supplements to prevent a deficiency)

Lactic Acidosis

This adverse reaction is relatively rare but could be quite serious if it develops. Notify your doctor immediately if you develop any of the following:

• Irregular heart rhythms or rapid pulse
• Lethargy
• Anxiety
• Low blood pressure
• Serious nausea and stomach pain

You can learn more about diabetes treatments in our Guide to Managing Diabetes. Share your own experience with metformin below.