Written by Timothy Aungst, PharmD | Reviewed by Amy B. Gragnolati, PharmD, BCPS
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Key takeaways:
- Metformin is a first-choice option for treating Type 2 diabetes. It’s also recommended for some people with prediabetes.
- Metformin side effects are manageable for most people. But there’s questions about whether metformin can cause long-term side effects, including memory loss and nerve damage.
- Long-term metformin use isn’t known to cause kidney damage or worsen polycystic ovary syndrome (PCOS). It’s also not known if metformin can help extend life expectancy or lower the risk of cancer.
Metformin is a common first-choice treatment for Type 2 diabetes. It helps lower your blood sugar levels and can lower your risk of cardiovascular events like heart attacks. It also has a low risk of causing harmful drug interactions and severe side effects. The American Diabetes Association (ADA) also recommends metformin for some people with prediabetes.
Generally, if you’re prescribed metformin, you’ll be on it long term. That could be many decades, unless you experience complications or changes to your health that require you to stop taking it.
However, metformin does have some side effects, and people often have questions about the safety of long-term use. Here, we’ll address some popular myths around metformin’s long-term side effects and explain some potential safety concerns.
Can long-term metformin use cause memory loss and dementia?
It’s unclear. Researchers have been investigating the connection between metformin and memory loss for over a decade. Several studies have highlighted a possible link between metformin use and a higher risk of developing dementia. Other studies have found the opposite: a lower risk of developing dementia in people using metformin.
Regardless of metformin use, research seems to show that diabetes itself more than doubles your risk of dementia. So, if you’re taking metformin and experience memory loss as a side effect, it could be your diabetes (and not the medication) that’s causing it.
Overall, the research on metformin and dementia is mixed and not definitive yet. Many clinicians would recommend the continued use of metformin at this time. Its protective role and benefits currently outweigh the unknown risk of dementia.
Can long-term metformin use cause kidney damage?
Metformin doesn’t cause kidney damage. The kidneys process and clear the medication out of your system through your urine.
If your kidneys don’t function properly, there’s concern that metformin can build up in your system and cause a condition called lactic acidosis. Lactic acidosis is when there’s a dangerous amount of lactic acid in the body. It can be life-threatening and is the main reason why your healthcare provider must monitor your kidney function.
Keep in mind that uncontrolled diabetes raises your risk of developing kidney problems. The use of medications like metformin can help keep your kidneys and other organs healthy over time.
Can long-term metformin use make PCOS worse?
No. Polycystic ovary syndrome (PCOS) is not a long-term side effect of metformin. PCOS is one of the most common causes of female infertility. PCOS is also a risk factor for developing Type 2 diabetes. So, it’s recommended that healthcare providers regularly check women with PCOS for diabetes.
Metformin is actually a treatment option for PCOS. It can be tried if hormonal contraceptives (birth control) and healthy lifestyle changes haven’t worked. PCOS can cause insulin resistance, which can lead to high blood sugar levels. Metformin combats this. Metformin can also help treat irregular periods and can be a good option for women with PCOS and Type 2 diabetes who cannot tolerate hormonal contraceptives.
Some people may be concerned that metformin can make PCOS worse or cause infertility. But there isn’t enough research to prove this. Although metformin isn’t recommended for every woman with PCOS, it’s recommended for women and adolescent girls with both Type 2 diabetes and PCOS. Some clinicians may even recommend that these women continue using metformin through pregnancy.
Can metformin cause anemia?
Yes. Anemia is a side effect of metformin. The medication can interfere with the absorption of vitamin B12, a vitamin you need to maintain healthy blood cells. Low vitamin B12 levels can lead to anemia and iron deficiency.
Your blood work should be monitored by your healthcare provider to make sure that you’re not seeing a significant drop in vitamin B12. If this happens, taking a vitamin B12 supplement may help. If you and your healthcare provider decide it’s necessary, stopping metformin should bring your vitamin B12 levels back to normal.
Can metformin cause nerve damage?
It’s possible but unlikely. Along with raising your risk for anemia, low vitamin B12 levels may also contribute to nerve damage (or neuropathy). This can lead to chronic nerve pain.
However, uncontrolled diabetes can also lead to neuropathy. If you’re taking metformin for Type 2 diabetes and experience neuropathy, it could be a symptom of your diabetes rather than a side effect of the medication.
Research on metformin causing nerve damage is mixed. It seems that while neuropathy can happen from diabetes itself, it’s unlikely that it’s a metformin side effect.
Can metformin help you live longer?
It’s unclear. A number of news articles have interviewed people who take metformin with the hope of living a longer and healthier life. These people don’t have diabetes, but they take metformin because they think it might lower their risk of cancer and make them healthier overall.
In the early 2000s, research showed that metformin extended life expectancy in mice, but its impact on human life expectancy is currently unknown. Some researchers believe that metformin may be effective in anti-aging, though research is ongoing. We need more human studies before determining whether metformin can extend life expectancy in people without diabetes.
Can metformin lower the risk of cancer?
It’s possible. People with diabetes may have a greater cancer risk. However, more recent research has shown that metformin may be effective in treating and preventing cancer. Studies published in 2015 and 2018 suggest that people taking metformin may have a lower risk for cancer, with some studies suggesting a reduced risk of 30% to 50%.
Some researchers have suggested that metformin lowers cancer risk by slowing or stopping tumor cell growth. However, this research is still limited. It’s also hard to tell if metformin itself lowered cancer risk in the supporting studies, because other treatments and interventions may have been involved. It’s unlikely that metformin will be prescribed to treat cancer at this time based on the currently available data.
Proven long-term side effects of metformin
Of those discussed above, low vitamin B12 levels is the only proven long-term metformin side effect. But, as mentioned, low vitamin B12 levels can cause other problems, including anemia. That’s why it’s important to go for all recommended blood tests while taking metformin. This will help your healthcare provider make sure your vitamin B12 levels aren’t dropping too low, helping to prevent other complications.
The bottom line
Most of the “myths” regarding long-term side effects of metformin are not cause for concern. However, some side effects, like anemia, are worth being aware of.
Generally, though, metformin is considered to be a safe and effective treatment for Type 2 diabetes and prediabetes. Metformin has been shown to lower the risk of cardiovascular events like heart attacks and help lower the risk of Type 2 diabetes complications like poor vision, impaired kidney function, and chronic nerve pain. These issues can appear after years of untreated diabetes. If you have diabetes and your provider prescribes metformin, discuss the benefits, side effects, and any concerns you have.
References
American Federation for Aging Research. (n.d.). The TAME trial.
Anisimov, V. N., et al. (2008). Metformin slows down aging and extends life span of female SHR mice. Cell Cycl
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