Is Metformin Safe? 

Metformin is the most commonly prescribed oral medication for treating type 2 diabetes, a condition arising from insulin resistance. Type 2 diabetes is a highly prevalent disease in which the body's cells don't respond like they should to the blood sugar-lowering hormone insulin.

While Metformin is primarily used for managing blood glucose (i.e. blood sugar) in people with type 2 diabetes, medical providers may prescribe the drug for off-label uses, such as to support heart health in certain patients and to treat polycystic ovarian syndrome (POCS).

However, you may wonder whether metformin is safe despite its widespread use. This article explains everything you need to know about metformin, including whether it's safe and what side effects you may experience when using the drug.

Understanding Metformin

Metformin, chemically known as N, N-dimethylbiguanide, is an oral drug approved by the Food and Drug Administration (FDA) in 1994 for treating type 2 diabetes (1). It is also sold under the brand names Glucophage, Riomet, Glumetza, and Fortamet.

Metformin belongs to a class of medications called biguanides, which work by preventing the liver from producing glucose, and improving insulin sensitivity, allowing the body to more effectively lower blood sugar by driving it into your body’s cells to use as energy or store for later. Metformin can also help reduce appetite by increasing the release of satiety-related peptides (2).

In addition, metformin offers cardioprotective effects, meaning it protects the heart and its arteries from disease or injury (3). This effect is particularly important in people with type 2 diabetes since blood sugar, when consistently elevated, can damage the heart, along with the kidneys, nerves, and other organs.

Conversely, metformin is not used to treat type 1 diabetes, a disease in which the body doesn't produce enough or any insulin; however, it is commonly prescribed in women who are diagnosed for the first time with diabetes during pregnancy (gestational diabetes).

Metformin comes in both immediate- and extended-release tablets and is typically prescribed with recommendations for lifestyle changes, such as nutrition counseling from a registered dietitian. The drug may also be prescribed alongside other medicines for treating diabetes.

Medical providers also prescribe metformin for uses not approved by the FDA. For example, medical providers prescribe metformin to restore fertility, reduce body weight, and decrease the occurrence of excess body hair in women with PCOS.

Regardless of the indication, metformin is unavailable over the counter and must be prescribed by a medical provider. It is not a controlled substance, however.

Is Metformin Safe?

Since obtaining FDA approval for the treatment of type 2 diabetes in 1994, numerous medical studies have assessed the safety of metformin, both in patients with type 2 diabetes and in patients for whom providers prescribe metformin off-label.

The majority of these studies have suggested that metformin has a strong safety profile and is generally well-tolerated in commonly prescribed doses (4). The safety of metformin has also been demonstrated in children and teens with obesity and type 2 diabetes (5).

One of the greatest concerns when prescribing antidiabetic drugs like metformin is the risk for hypoglycemia (read: low blood sugar). However, incidences of low blood sugar and other adverse events tend to be significantly more likely with other types of commonly prescribed antidiabetic drugs, like glinides, compared with metformin (6).

Studies have also demonstrated that metformin is safer and more efficacious than other drugs commonly prescribed for treating type 2 diabetes and conditions for which it's prescribed off-label (7, 8, 9). For example, a review of 17 studies involving nearly 3,000 women with PCOS found that metformin does not increase complications like preterm delivery; in fact, it decreases the risk of them (10).

While generally safe for most people, metformin may not be safe for others since it can increase the risk of a condition called lactic acidosis. Lactic acidosis from taking metformin occurs when excessive levels of the drug accumulate in the bloodstream and cause metabolic acidosis.

Metabolic acidosis is a condition in which excess lactic acid builds up in the body and impairs important bodily functions. Risk factors for metformin-associated lactic acidosis include (11):

• impaired kidney function or kidney disease based on blood creatinine concentration

• liver disease

• use of other medicines, such as certain diuretics

• age 65 years or older

• undergoing a surgery or other type of procedure

• excessive alcohol intake

• congestive heart failure

Symptoms of lactic acidosis from taking metformin are usually nonspecific, such as feeling fatigued or restless.

Potential Side Effects of Metformin

Studies have demonstrated that metformin has a strong safety profile, but the drug can cause minor adverse side effects in some people. The most common adverse effect of metformin is diarrhea, but others include (11):

• nausea or vomiting

• excessive gas/flatulence

• lack of energy

• indigestion

• stomach discomfort

• headache

Tell your doctor if you experience any of these symptoms while taking metformin. To avoid stomach discomfort or nausea, it's recommended that you take metformin with food.

Another common side effect of metformin is the depletion of vitamin B12 levels. Your body needs vitamin B12 to support nervous system health, red blood cell formation, DNA production, and various metabolic reactions.

Taking metformin can deplete vitamin B12 levels by interfering with its absorption from food, but this depletion usually isn't enough to lead to clinical symptoms of a deficiency (12).

However, if you follow a vegetarian diet, you should tell your doctor as will be at an increased risk of developing a deficiency since the primary dietary sources of the vitamin are animal products.

With long-term metformin use, medical providers usually measure vitamin B12 levels via a blood test every year or so in patients receiving metformin.

Benefits of Metformin

Metformin treatment offers numerous health benefits, which are further discussed in the following sections.

It lowers blood sugar

The best and most well-known benefit of metformin is that it lowers blood sugar, namely by enhancing insulin sensitivity to increase the uptake of glucose to your body's cells from the blood. For this reason, medical providers prescribe it as a first-line treatment for type 2 diabetes.

In many instances, metformin alone can effectively lower blood sugar levels, but at other times medical providers prescribe additional antidiabetic medications alongside it, especially in people with poorly controlled diabetes.

Many medical providers also prescribe metformin in patients with prediabetes — a condition in which blood sugars are high but not yet at the level of type 2 diabetes.

When prescribed to patients with prediabetes, metformin can control blood sugars well enough to prevent the advancement to type 2 diabetes.

It supports weight loss

In people with diabetes or PCOS, metformin may promote moderate weight loss by decreasing appetite (13). While not all studies report significant weight loss with the drug, incorporating lifestyle changes such as following a low-calorie diet may support metformin's weight loss effects.

Even small changes, such as cutting back on sugary beverages or aiming to consume protein with each meal and snack, can result in significant improvements in blood sugar control.

Considering that muscle is the largest disposal of blood sugar following a meal, exercise — namely resistance or weight training — also offers significant benefits for supporting healthy blood sugar levels.

It protects the heart

Cardiovascular disease (heart disease) is the number one cause of death worldwide. By lowering risk factors for cardiovascular disease such as triglyceride levels — fat in the blood — blood glucose levels, blood pressure, and to a minor extent, body weight, metformin offers cardioprotective effects.

Indeed, metformin has been shown to decrease the incidence of heart attacks in newly diagnosed patients with diabetes (14). In patients with heart disease, metformin has also been shown to reduce the risk of death or other adverse health outcomes related to the disease (14).

It can treat PCOS

PCOS is a common hormonal condition that can cause infertility, acne, insulin resistance, and other health issues in women.

Owing in part to its ability to improve insulin resistance, metformin is commonly prescribed as an effective treatment for PCOS to improve fertility and reduce androgen — or male-sex hormone — levels, which, when elevated, can lead to excess hair growth and acne (15).

Metformin has also been shown to reduce body weight and waist circumference in women with the condition (15).

Other uses

Increasing research suggests that metformin has potential antiaging, anticancer, and neuroprotective — serving to protect nerve cells from damage — effects (16, 17, 18).

Metformin is believed to exert these effects by reducing oxidative stress and inflammation caused by high blood sugar and other metabolic stressors.

Safety Measures When Using Metformin

Taking metformin is generally safe for most people.

However, because it can increase the risk of lactic acidosis in certain people, it's important that your medical provider assess your risk for the condition and know your full medical history.

Your medical provider may still prescribe metformin-containing medicines if you have one or more risk factors for lactic acidosis, but they will want to monitor you more closely and frequently.

Even if you aren't at risk for developing lactic acidosis, it's important that you know its symptoms, which include:

• fast or shallow breathing

• increased drowsiness

• restlessness

• muscle aches and pain

Contact your doctor immediately if you experience any of these symptoms while using metformin.

Your medical provider will also want to regularly measure your renal function and hemoglobin A1C, which measures your average blood sugar levels over the past three months.

Because a vitamin B12 deficiency can arise from long-term metformin use, your medical provider should also frequently measure your levels, especially if you are already at risk for a deficiency due to being a vegetarian or because of other reasons.

It's possible to have an allergic reaction to metformin, so you should also let your doctor know if you experience signs of reaction such as a skin rash, hives or welts, itching, redness of the skin, or rapid breathing.

Always take your metformin as prescribed by your medical provider, and let them know of any missed doses.

FAQ - Frequently Asked Questions

What are the benefits of taking metformin

Metformin affords many benefits, with its ability to lower blood sugar by improving insulin sensitivity and decreasing the liver's production of glucose.

Metformin also supports weight loss, protects the heart, treats PCOS, and is well-tolerated and relatively inexpensive.

Is metformin safe for pregnant women?

Metformin is generally considered safe for pregnant women and may improve pregnancy outcomes, especially in women with gestational diabetes.

Limited research reports that metformin can be transferred to breastmilk, but there is insufficient data to determine the effect on the breastfed infant (11).

Can metformin cause harm?

Metformin has a strong safety profile and is well-tolerated. However, metformin can increase the risk of developing lactic acidosis — a potentially fatal condition — in certain people.

For this reason, metformin may not be safe in patients with the following risk factors:

• impaired kidney function or kidney disease based on blood creatinine concentration

• liver disease

• use of other drugs, such as certain diuretics

• age 65 years or older

• undergoing a surgery or other type of procedure

• excessive alcohol intake

What are the side effects of metformin?

The most common side effect of metformin is diarrhea, but nausea or vomiting, excessive gas, lack of energy, indigestion, stomach discomfort, and headache have also been commonly reported with its use.

It's a good idea to tell your doctor if you experience any of these symptoms while using metformin.

What is the recommended dosage for metformin?

The recommended starting dose for metformin is 500 mg daily with the evening meal.

Your medical provider can then increase your dose by 500-mg increments as needed to effectively control blood sugar up to a maximum dose of 2,500 mg daily.

Are there any alternatives to metformin?

Metformin is the first-line treatment for type 2 diabetes.

However, if it's unsafe for you to take or it's not effective enough, your medical provider may suggest an alternative such as GLP-1 agonists like Ozempic (semaglutide) or SGLT2 inhibitors like Jardiance (empagliflozin).

Key Takeaways on Metformin

Metformin is the most commonly prescribed drug to treat diabetes — specifically type 2 and prediabetes. It lowers high blood sugar by decreasing the liver's production of glucose and increasing your body's cellular response to the blood glucose-lowering hormone insulin.

Beyond its use to treat diabetes, metformin is commonly prescribed off-label for its cardioprotective effects and to treat PCOS. Metformin has a strong safety profile and is well-tolerated by most people, but it can cause diarrhea and other side effects such as indigestion or stomach upset.

In people with certain risk factors, such as severe kidney problems, metformin can also cause a potentially deadly condition in which too much lactic acid accumulates in the blood.

Regular monitoring by your medical provider of various medical tests such as hemoglobin A1c, renal function, and vitamin B12 status is important while taking metformin or metformin-containing medicines to ensure safe use.