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Metformin: New Benefits (and Risks) For This Old Diabetes Drug

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If type 2 diabetes is part of your life—whether you have the condition or are at risk of developing it—you’ve probably heard of a drug called metformin. Perhaps your doctor has told you about it, has recently started you on it or has been prescribing it to you for years to keep your blood sugar under control.

It’s no newbie. Metformin has been available by prescription in the US for more than 20 years and in Europe for more than 40 years. US doctors write nearly 60 million prescriptions a year. It’s recommended as the go-to-first prescription for people with diabetes by the American Diabetes Association, the American Association of Clinical Endocrinologists and the American College of Physicians.

Yet, in many ways, metformin remains a mystery. We know broadly but still not exactly, how it works. Even more surprising, new health benefits—and side effects—keep popping up. In fact, we’ve only recently learned that metformin might protect the heart, fight cancer and even boost longevity. On the other hand, it can, rarely, lead to a potentially fatal side effect, and it can even make a common diabetes complication worse.

It’s time to take a closer look at metformin.

MEDIEVAL FLOWER REMEDY, MODERN DRUG

In medieval times, herbalists prescribed Galega officinalis—the bloom of the French lilac, also known as goat’s rue and Italian fitch—for patients with what we now recognize as diabetes. In the 1950s, medical researchers identified a compound in the lilac, metformin, that appeared to reliably and safely reduce high blood sugar. Metformin became widely available in Europe in the 1970s and was approved by the US Food and Drug Administration in 1995 to treat type 2 diabetes. Some combination prescriptions include metformin with other prescription medications.

HOW IT WORKS

We now know what medieval herbalists didn’t—metformin increases the sensitivity of muscle and fat tissue to the hormone insulin. That makes it easier for your body to drive blood glucose (aka blood sugar) into the body’s cells where it can be metabolized into energy. It also cuts the amount of sugar that the liver pushes out into the bloodstream. The exact mechanisms aren’t known, but the result is lower blood sugar.

WHY IT’S THE BEST FIRST DRUG FOR DIABETES

There are three great things about metformin that set it apart from other diabetes medications. It is very inexpensive. It won’t cause your blood sugar to plummet, as some diabetes drugs do. That’s a complication that can range from merely bothersome to so dangerous that it lands you in the hospital. Metformin doesn’t have that risk.

And it doesn’t cause weight gain as many other diabetes drugs do—and may even help some people lose a few pounds. One explanation for this is that the drug enhances the effect of the appetite-suppressing hormone leptin. The weight story is important because many diabetes patients stop taking medications that make them gain weight. Metformin doesn’t present that problem.

CANCER PREVENTION…AND LONGEVITY?

It’s amazing that this French lilac has been a diabetes remedy for centuries, and metformin has been a drug for more than 50 years, yet every few years there’s a new study highlighting a potential new benefit—or entirely new use. Promising findings…

• Cardiovascular protection. Some observational studies have reported that people with type 2 diabetes who take the drug are less prone to heart disease than those who don’t.

• Cancer treatment. Metformin’s potential to prevent, treat or enhance other treatments for certain cancers has recently emerged. These are based on small, preliminary studies, however. The drug’s ability to reduce both blood sugar and insulin levels may play a part in its possible anticancer properties.

• Longevity. The latest area of research is the potential for metformin to improve longevity by slowing physiological aging and increasing lifespan. These studies are based on preliminary observations using animal models (roundworms). Much more research in animals—and eventually, humans—will be needed to determine if metformin can have a similar effect in humans…with or without diabetes.

SIDE EFFECTS, OLD AND NEW

The most common complaint with metformin is that it can cause gastrointestinal issues such as abdominal discomfort and diarrhea. Although this may sound minor, it keeps some people from being able to take the drug. An extended-release metformin is available, and in some patients, this version may be better tolerated. Other side effects include…

• A very rare but potentially fatal reaction. It has been known for many years that if a patient’s kidney function is poor when they are taking metformin, there is an increased risk for lactic acidosis, a condition in which too much lactic acid builds up in the blood. This metformin side effect occurs in fewer than 10 out of every 100,000 patients—0.005%—but it’s fatal half the time it occurs. That’s why your doctor should test you regularly for kidney function if you’re taking metformin. Metformin does not cause kidney damage—it is just not safe to take if a patient already has a significant impairment in his or her kidney function.

• B-12 deficiency. A recently discovered side effect of metformin, particularly after long-term use, is a deficiency of vitamin B-12. People who are B-12 deficient for a long time may develop cognitive problems and even dementia. Ironically, a B-12 deficiency can also contribute to neuropathy—a burning sensation or lack of sensation in the legs and feet. This common diabetes symptom is usually the effect of high blood sugar causing nerve damage, but B-12 deficiency can cause leg neuropathy or make it worse. It can also cause a form of anemia. If you have type 2 diabetes, have been taking metformin for a long time—and especially if you are experiencing neuropathy or cognitive issues—ask your doctor to check your B-12 level. The fix can be as simple as a B-12 pill or a monthly B-12 injection.

Generally, metformin is a safe medication. Under the care of a physician, it is safe to take this drug for decades so long as a patient’s kidney function remains good and B-12 levels are checked in the appropriate clinical situations, such as in cases of longstanding use, anemia, neuropathy or cognitive issues.

IS METFORMIN RIGHT FOR YOU?

Now that you’ve got the scoop on this drug—its past, present and future potential—how can you tell if it’s right for you? The following are general guidelines, which may inform you as you tailor your individual treatment plan with your doctor…

If you have type 2 diabetes. You may be able to control your blood sugar with lifestyle changes alone, including a healthy diet, weight loss and exercise. However, it is generally recommended that patients start metformin along with lifestyle changes at the time of type 2 diabetes diagnosis. It’s an important discussion to have with your doctor.

If you are at risk for developing type 2 diabetes. People at risk include not only those with prediabetes but also women who developed diabetes during pregnancy (gestational diabetes), because they have a greatly increased risk of developing type 2 diabetes over their lifetimes. It is best to try lifestyle modifications before considering metformin. If that isn’t working for you, ask your doctor about metformin.

If you are a woman with polycystic ovary syndrome (PCOS). This condition increases the risk of developing type 2 diabetes and often leads to infertility. It is marked by high insulin levels, which contribute to a hormonal imbalance. In patients with PCOS, metformin, which tends to reduce insulin resistance, is sometimes prescribed in an attempt to restore ovulation and to improve fertility. If pregnancy is confirmed, metformin is usually continued for at least the first trimester. Always talk with your doctor about your treatment options.

There are, however, practical concerns to be aware of if you don’t have diabetes but are taking metformin. Insurers tend to assume that anyone on metformin may have diabetes…even if you’re taking it to prevent diabetes. That could affect medical and life insurance coverage. If you are not diabetic but need to take metformin, you may need your doctor to write a letter to your insurer confirming that you do not have diabetes. While there may be many medical reasons to take metformin beyond just type 2 diabetes, a thorough discussion about the role of metformin therapy, and the risks versus benefits, should take place before a patient starts any medication, including metformin.

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Source: Kevin M. Pantalone, DO, Endocrine Certification in Neck Ultrasound (ECNU), FACE, is a staff endocrinologist at Cleveland Clinic and serves as the director of clinical research for Cleveland Clinic’s department of endocrinology, diabetes and metabolism. Dr. Pantalone’s clinical focus is on the glycemic management of type 2 diabetes, and his research interests are related to the adverse effects of diabetes therapies. Date: July 5, 2017 Publication: Bottom Line Health
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