Metformin: Uses, Dosage and Common Side Effects

Metformin is an FDA-approved prescription medication to treat high blood sugar in patients with type 2 diabetes. It has also been successfully used to treat polycystic ovary syndrome (PCOS) and prediabetes.

Weight loss is a potential side effect of metformin, which has sparked curiosity about off-label usage. This article will discuss possible uses of metformin in a variety of patients as well as potential side effects.

What is Metformin?

Metformin is an antihyperglycemic and antidiabetic agent that is FDA-approved for treating type 2 diabetes. This medication needs to be prescribed by a physician. In the U.S., you cannot buy metformin over the counter. It may be used alone or with other medications to control the amount of glucose in the blood and increase the body's response to insulin. It belongs to a class of drugs called biguanides.

Metformin brand names include Glucophage, Riomet, Glumetza, Glucophage XR, and Fortamet. Metformin comes in the form of a tablet, extended-release tablet, or oral suspension. In the U.S., you can only buy metformin with a prescription.

What is metformin used for?

Metformin is used to treat type 2 diabetes. However, studies over the last few decades have also shown that metformin may be used to treat other diseases and conditions, have cardioprotective qualities, as well as reduce some of the effects of aging.

Research on metformin is still ongoing for the following conditions / benefits:

However, these are considered off-label uses of the drug. More high-quality, large-scale trials are needed before researchers can draw firm conclusions about metformin's role in these conditions.

How does metformin work?

Despite being in use for over 60 years, we still do not fully understand how metformin works in the body.

Researchers have shown that metformin lowers both basal and postprandial blood glucose levels by reducing the absorption of glucose in the intestine. It also improves insulin utilization by stimulating the 5'-AMP-activated protein kinase and modulating lipid metabolism.

Recent research also suggests that the drug can alter the energy metabolism of the cell and influence tumorigenesis by reducing insulin levels and inducing energetic stress.

In PCOS, metformin can help normalize the menstruation cycle through its action to decrease insulin levels, which then lowers luteinizing hormone and androgen levels.

Metformin also acts as an appetite suppressant and has led to modest weight loss in some patients treated for type 2 diabetes.

Metformin side effects

Metformin side effects are typically mild, occurring in roughly 25% of patients. It's rare for a patient to need to stop taking the medication because of side effects. Starting with a small metformin dosage is one way to avoid side effects. The best time to take metformin is after meals and before bed. Extended-release metformin may also help reduce side effects.

The most common side effect of metformin appears to be GI upset and, more specifically, diarrhea. For many, diarrhea subsides the longer they're on the medication.

Some side effects of metformin are seen as desirable, such as weight loss. While weight loss is generally modest on metformin, the drug does appear to help people keep off those few pounds.

Common side effects

Metformin is generally well-tolerated in patients under 80 and without kidney disease.

The most common side effects of metformin are:

Taking metformin extended-release capsules can help alleviate some of these side effects.

Serious side effects

Metformin can lead to more severe side effects in some patients, especially those with poor kidney function. In some cases, studies have drawn conflicting conclusions about the side effects of metformin. For example, some studies appear to show an increased risk of Alzheimer's when taking metformin, while others have found it may lower the risk of dementia and Alzheimer's.

Rare side effects of metformin that require a doctor's attention include:

• Fast or shallow breathing
• Coldness
• Slow heartbeat
• Jaundice
• Serious allergic reactions

Lactic acidosis

In some cases, too much metformin can cause a serious condition called lactic acidosis. However, researchers have pointed out that these risks may be overblown and are quite rare.

The risk of lactic acidosis while taking metformin appears to be highest in this with impaired kidney function. But in these cases, it can be fatal.

B12 deficiency

Studies have shown that anywhere from 6% to 30% of patients taking metformin show a related vitamin B12 deficiency. Researchers believe metformin reduces vitamin B12 absorption in the gastrointestinal tract. Therefore, patients on metformin should have their B12 levels monitored.

Hypoglycemia

Taking too much metformin can result in hypoglycemia due to increased glucose consumption secondary to anaerobic metabolism. Other possible causes include decreased liver glucose production and decreased glucose absorption.

Avoiding hypoglycemia on metformin requires close monitoring of blood glucose. However, since it's a type 2 diabetes medication, patients are likely being monitored.

Metformin drug interactions

Talk to your doctor about all medications and supplements you take if you are prescribed metformin. It's vital to mention any other medications that lower blood sugar (such as insulin) since they may cause hypoglycemia.

You may also want to avoid drugs that increase blood sugar since they can counteract the effects of metformin. These can include:

• Estrogen-containing birth control pills
• Some thyroid medications
• Antipsychotics
• Diuretics
• Corticosteroids, like prednisone

Metformin may also interact with carbonic anhydrase inhibitors, cimetidine, and alcohol to increase the risk of lactic acidosis.

Combining metformin with other drugs

Tell your doctor if you are taking diabetes medications labeled as sulfonylureas and meglitinides, such as:

Above-mentioned drugs can make your blood sugar drop too low.

Medications often used alongside metformin to regulate glucose include dulaglutide (Trulicity), alogliptin (Kazano), and sitagliptin (Januvia).

Some medications prevent your body from removing metformin, which causes it to build up and could lead to lactic acidosis. These medications include dolutegravir (Tivicay), ranolazine (Ranexa), vandetanib (Caprelsa), and cimetidine (Tagamet HB).

Combining metformin with semaglutide medications like Ozempic and Rybelsus to suppress appetite and lose weight in those with obesity-induced diabetes. Patients should be monitored for disordered eating (such as anorexia) and vitamin deficiencies.

Metformin dosage

Metformin is available as a liquid suspension as well as regular and extended-release tablets.

Tablets typically come in 500 mg, 850 mg, and 1000 mg doses, while extended-release tablets come in 500 mg and 750 mg doses.

It is possible to overdose on metformin if you take too much (amounts larger than 50 grams). Hemodialysis is recommended for metformin overdose.

How to take metformin

The starting dose of metformin tablets is 500 mg orally twice a day or 850 mg once a day. Take metformin with meals. A metformin dosage can be increased in increments of 500 mg per week or 850 mg every two weeks.

Patients often wonder when to take metformin, before or after meals. Metformin is best tolerated when taken with three meals a day.

Foods to avoid while taking metformin include those that will lead to a spike in blood sugar, such as white bread and pasta, candy, desserts, and soda. These foods will make it harder for metformin to stabilize your blood sugar.

Other commonly asked questions about how to take metformin include:

• How much metformin is too much? The maximum recommended dose of metformin is 2000 to 2550 mg per day, according to a doctor's recommendation.
• Can you overdose on metformin? Yes, it is possible to overdose on metformin, although it is quite rare. Most overdoses are intentional and result in lactic acidosis or metformin-associated hypoglycemia. If you are under a doctor's care and do not have renal insufficiency, the possibility of developing these conditions is low since your doctor will ensure any other medications you are taking do not increase the effects of the drug.
• How long does it take for metformin to work? Metformin typically begins working to lower blood sugar in the first weeks of starting a prescription.

Using Metformin during pregnancy

Metformin can increase a person's chances of becoming pregnant. There are no apparent risks associated with taking metformin while pregnant. In fact, the risk to the mother and fetus is more significant if the mother has uncontrolled type 2 diabetes.

Studies suggest that females with insulin resistance associated with polycystic ovary syndrome (PCOS) may experience improved fertility with metformin.

What are the signs that metformin is working?

Since metformin is prescribed to control glucose and improve insulin resistance, testing your glucose levels for signs of improvement is the best way to tell if metformin is working.

People taking metformin may also notice more energy and a reduction in diabetes symptoms (like impaired vision and frequent urination).

Patients don't typically notice the results of metformin in the first week. It takes two weeks or more to start experiencing measurable benefits.

Alternatives to metformin

If you are not a suitable candidate for type 2 diabetes treatment with metformin, there are alternatives. These include:

• SGLT-2 inhibitors. Canagliflozin, dapagliflozin, and empagliflozin, are FDA-approved to lower blood sugar in adults with type 2 diabetes.
• GLP-1 Receptor agonists. Liraglutide and semaglutide, stimulate the release of insulin and suppress glucagon secretion when appropriate.
• Sulfonylureas (SFUs). They increase insulin release and are one of the oldest classes of drugs used to treat type 2 diabetes.
• Thiazolidinediones (TZDs). They are insulin-sensitizing medications that reduce glucose.

Lifestyle changes that reduce the risk of type 2 diabetes, such as weight loss, may also be an alternative to metformin in some patients.

Natural metformin alternatives

Some non-prescription, natural alternatives to metformin might act in the same way to help treat type 2 diabetes.

For example, berberine has been shown to lower blood sugar levels to a similar extent as metformin. It also assists in the breakdown of carbohydrates.

Inositol is another possible alternative to metformin and a B vitamin. The types of inositol helpful for type 2 diabetes and PCOS are myo and d-chiro inositol due to their ability to reduce insulin resistance and help restore ovulation.

Ceylon cinnamon has also been shown to increase insulin sensitivity by lowering fasting blood sugar. Similarly, the amino acid N-Acetyl Cysteine (NAC) may improve insulin sensitivity and protect cells from damage.