Side Effects of Metformin: Watch Out for These Signs

Metformin has long been used as a low-cost, daily prescription medication for treating Type 2 diabetes and high levels of insulin resistance. It belongs to a class of diabetes medications known as biguanides. It comes in immediate or extended-release formulations. It also has off-label uses for treating polycystic ovary syndrome (PCOS) and to help induce weight loss for people living with prediabetes.

“When you have insulin resistance, your muscles, fat and liver cells aren’t able to use that insulin efficiently. So, metformin helps your body be more sensitive to the insulin that it already has,” explains endocrine clinical pharmacist Diana Isaacs, PharmD.

“Instead of a ton of glucose sitting in the bloodstream where it could do damage, metformin helps that glucose gets into the cells so it could be used for energy.”

In general, most people handle metformin with little to no mild side effects. In rare cases, severe side effects like lactic acidosis are possible and require immediate medical treatment. Here’s what we know.

What are the side effects of metformin?

When you first start taking metformin, you may experience some mild gastrointestinal side effects that include:

• Nausea
• Diarrhea
• Increased gas
• Bloating
• Stomach pain

Other common side effects include:

• Weight loss
• Headaches
• Metallic taste in your mouth

If you’ve taken metformin for four years or more, you’re also at higher risk for vitamin B12 deficiency.

“If you don’t have enough vitamin B12, that can lead to neuropathy, or the numbness and tingling of your hands and feet and can even cause memory problems,” explains Dr. Isaacs. “I suggest anyone who’s been on it for four years or more to ask their healthcare provider to check their vitamin B12 levels.”

How to avoid them

To reduce the chances of these side effects, Dr. Isaacs recommends:

• Taking metformin with food and avoid taking it on an empty stomach
• Start out on smaller doses and increase over time as needed

Gastrointestinal side effects like nausea and diarrhea tend to resolve on their own once your body gets used to taking metformin. These common side effects are also less common on lower doses and with the extended-release versions of metformin.

“If you start off on a higher dose, you’re more likely to have these side effects,” notes Dr. Isaacs. “If you stop taking it for some reason and you go right back to that higher dose, you might also notice more of these side effects.”

As for anyone concerned about vitamin B12 deficiency, there are numerous ways to boost your levels through foods high in vitamin B12 and supplementation.

“With metformin, it’s really about making sure you have food in your stomach and making sure you’re following a healthy meal plan,” Dr. Isaacs emphasizes.

Serious side effects

More serious side effects include lactic acidosis and hypoglycemia, though these tend to occur in very specific populations.

When you have too much metformin in your body, it can result in lactic acidosis. This is a life-threatening condition caused by a pH imbalance and too much lactic acid in your bloodstream. When this happens, it can deprive your tissues and organs of necessary oxygen and lead to heart failure, liver dysfunction, sepsis and shock.

Symptoms of lactic acidosis can come on suddenly or slowly progress over time, and may include:

• Extreme fatigue and weakness
• Muscle pain and body aches
• Trouble breathing
• Dizziness
• Fever
• Irregular heart rate

“Lactic acidosis is a very rare side effect,” clarifies Dr. Isaacs. “It’s more likely to occur if there are super high levels of metformin in the bloodstream and someone has reduced kidney function where it’s not being cleared out.”

Because of this, if you have kidney disease or other kidney conditions, notify your healthcare provider before taking metformin.

Hypoglycemia, or low blood sugar, can also be life-threatening if left untreated. Metformin doesn’t usually cause hypoglycemia on its own unless it’s taken in combination with insulin or other diabetes medications like sulfonylureas, which also raise your risk for hypoglycemia.

Early signs of hypoglycemia include:

• Shaking
• Weakness
• Sweating or chills
• Extreme hunger
• Faster heart rate
• Dizziness
• Confusion

Why might doctors not recommend metformin?

In most cases, metformin is safe to take. But healthcare providers may not prescribe metformin in a few different scenarios.

For starters, metformin tends to come in larger pill form, so if you have difficulty swallowing pills, this may not be the medication for you.

If you have other conditions beyond diabetes, newer medications may be more effective.

“Now, we have GLP-1 agonists and SGLT 2 inhibitors that have been shown to be just as effective, but they also have additional benefits outside of diabetes that offer protection from kidney disease, cardiovascular disease and heart failure,” shares Dr. Isaacs.

Otherwise, metformin is safe and effective on its own for treating Type 2 diabetes, and can even be combined with other diabetes medications, including insulin.

“Insulin has more of a risk for hypoglycemia and it involves injections, which people don’t love doing,” Dr. Isaacs adds. “But in my opinion, almost everyone, unless they have a reason or they’ve had side effects from it, should be OK with metformin. It’s a very effective medication for lowering glucose and overall has minimal side effects.”