What You Should Know About Metformin HCL

Metformin hydrochloride, aka metformin HCL, is an oral medication primarily prescribed to help people with type 2 diabetes lower their blood sugar. Metformin HCL 500 mg is the lowest dose of this medication.

Metformin HCL 500 mg is an extended-release medication for type 2 diabetes. Credit: PIKSEL/iStock/GettyImages

The medication is also sold as Fortamet, Glucophage XR and Glumetza. It is different from regular metformin in that it is an extended-release medication.

In a 2019 position statement, the American Diabetes Association (ADA) identifies metformin as a first-line medication for type 2 diabetes, as it is typically very effective with very few side effects. But for those people who do experience side effects from regular metformin, metformin HCL may be a good option because its extended-release formula makes it easier on the gastrointestinal tract.

How Does Metformin HCL Work?

Glucose, aka blood sugar, is the body's main source of energy. The body converts the carbohydrates in food into glucose, and the hormone insulin helps move the glucose from the blood into the cells. Through this process, insulin lowers blood sugar levels.

People with type 2 diabetes, however, are less sensitive to the effects of insulin; their cells can't use it properly, which is a condition called insulin resistance. This leads to a buildup of glucose in the bloodstream, aka high blood sugar.

Read More: Normal Blood Sugar Range After Meals

Regular metformin and metformin HCL both lower blood sugar through the same mechanism, as described by a study published in the November 2013 Pharmacogenet Genomics. They increase the muscle cells' insulin sensitivity, which enables more glucose to get into the cells where it belongs. They also reduce the amount of glucose produced by the liver. (When the body isn't getting energy from food, such as between meals or overnight, the liver steps in and supplies the body with glucose instead, per the University of California, San Francisco.) By limiting the amount of glucose released by the liver, both types of metformin lower blood sugar levels around the clock.

Metformin vs. Metformin HCL

Metformin HCL is different from regular metformin in that it is an extended-release medication. This can have a number of benefits, according to Elizabeth Halprin, MD, clinical director of adult diabetes at the Joslin Diabetes Center. "Extended-release metformin can be taken once a day instead of twice," she explains. "[Because of that], it may have fewer GI side effects."

This is because metformin HCL is steadily metabolized over 24 hours as opposed to regular metformin's 12. The gradual release rate helps reduce the risk of adverse side effects because it ensures that the medication isn't absorbed by just one concentrated area of the intestine, but rather is distributed throughout the entire GI tract, as explained by a review published in the January 2016 edition of Diabetologia.

Read more: Are There Any Herbal Alternatives to Metformin?

Side Effects of Metformin HCL

According to the ADA, the side effects of regular metformin typically affect the the GI tract. Metformin HCL can help reduce these symptoms, but they may still occur, especially when first starting the medication. Once the body has adjusted, the dose can be increased as needed.

The most common metformin HCL side effects include:

  • Diarrhea
  • Nausea
  • Vomiting
  • Gas
  • Abdominal pain

Metformin and Hypoglycemia

Hypoglycemia, aka low blood sugar, is a common problem for people with type 2 diabetes who take medications that lower their glucose levels (such as insulin or diabetes pills in the class called sulfonylureas). It is rare in people who are only taking metformin to manage their blood sugar, because metformin does not increase insulin levels.

However, metformin-related hypoglycemia can happen under certain circumstances. According to the U.S. National Library of Medicine, hypoglycemia can occur if the person taking metformin hasn't eaten enough, especially if they are engaging in strenuous activity. Alcohol consumption can also cause hypoglycemia in those on metformin. Hypoglycemia is also more likely to occur if metformin is taken in addition to diabetes medication that increases insulin levels, such as sulfonylureas or insulin injections.

Vitamin B12 Deficiency and Anemia

According to an ADA study published in February 2012, long-term use of both types of metformin can lead to a decrease in serum B12 concentrations, causing vitamin B12 deficiency over time.

Vitamin B12 is crucial for the production red blood cells. If the body doesn't have enough healthy red blood cells, anemia may result. Therefore, it is recommended that B12 levels be checked in those who have used metformin long-term, and especially in those with anemia or peripheral neuropathy.

Read more: Foods to Eat While Taking Metformin

Metformin-Associated Lactic Acidosis (MALA)

When the body uses glucose as energy, it creates lactic acid as a byproduct. Metformin causes the body to produce more lactate, which is the compound that makes lactic acid. Normally, the body is able to safely clear lactic acid. But if too much lactic acid builds up in the blood, it can result in lactic acidosis, a condition that can be fatal if left untreated.

MALA is extremely rare. According to a study published in the February 2016 Metabolism, it occurs in fewer than 10 patients out of every 100,000 per year.

The signs and symptoms are often nonspecific and can appear to be symptoms of a number of medical conditions. According to the U.S. National Library of Medicine, the symptoms of MALA can include:

  • Lethargy and/or unusual tiredness
  • Nausea
  • Vomiting
  • Weakness
  • Abdominal pain and/or stomach discomfort
  • Difficulty breathing
  • Muscle cramping
  • Fast heart rate
  • Diarrhea

Alcohol consumption can raise the risk of MALA because alcohol impairs liver function, making it even harder for the liver to clear lactic acid from the body. A small study published in Europe PMC in January 2013 found that alcohol consumption appeared to be the leading cause of lactic acidosis for people with diabetes. (Remember, however, that MALA is rare.)

A study published in the January 2013 issue of the Canadian Medical Association Journal found that intravenous contrast dye (often used in medical scans, such as CT scans) was also associated with an increased risk of MALA.The dye can put strain on the kidneys, impairing their ability to remove lactic acid from the blood. Because of this, experts at the University of Michigan recommend that patients on metformin stop taking the meditation the day of their contrast study, and wait 48 hours before taking metformin again.

How to Take Metformin HCL

The dosages for metformin HCL are listed on the U.S. National Library of Medicine as 500 milligrams, 850 milligrams and 1,000 milligrams.

The medication is taken once a day, typically with the evening meal. The Mayo Clinic states that it's important to take metformin with food to reduce the risk of adverse GI side effects. Taking it in the evening also helps further ensure that blood sugar levels won't spike overnight.

Is This an Emergency?

If you are experiencing serious medical symptoms, seek emergency treatment immediately.
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