Metformin Side Effects | When and Why is Metformin Used?

Metformin Side Effects: Is There Any to Worry About

Keeping blood sugar levels at normal or close to normal is essential in preventing long-term health problems such as heart disease, vision loss, and kidney disease. More than 133 million Americans have diabetes and face this challenge. (1-2)

If blood sugar normal level is not achievable with diet and a healthy lifestyle, medications such as metformin can help. Metformin has been shown to be effective and safe and, at the same time, may reduce the risk of cardiovascular events and death. (3-4)

However, diarrhea, nausea, or vomiting are side effects that bother some of the patients. While these possible side effects may go away after a period and are not that serious, lactic acidosis is rare but fatal in about half of the cases. (3)

Therefore, long-term diabetes management with metformin requires an understanding of possible side effects and prompt action in some events.

This article is all about metformin’s side effects. Learn the signs that can help you manage adverse reactions and ask for medical care on time.

When and Why is Metformin Used

Before learning about possible side effects, it is good to know when metformin is recommended. In diabetes type II, the metformin therapeutic goal is to decrease fasting plasma glucose and glycosylated hemoglobin levels (A1C – the average blood sugar level over the past 2 or 3 months) to normal or near normal.

To achieve the therapeutic goal, the manufacturer recommends the lowest effective dose of metformin as monotherapy or in combination with sulfonylurea or insulin (3). The American Diabetes Association recommends a combination of metformin with other oral antidiabetics as a higher-efficacy approach for a greater likelihood of achieving glycemic goals in its latest edition of Standards of Care in Diabetes from 2023 (4).

Fasting blood sugar is the level of glucose measured after an overnight fast, and the normal value is 70 – 99 mg/dL. The A1C test measures blood sugar at any time, and results below 5.7% (99 mg/dL) indicate normal values (1).

Following the FDA approval and American Diabetes Association guidelines, metformin is used alone or in combination to achieve and maintain treatment goals in type II diabetes. Metformin therapy can continue upon insulin is initiated as a next treatment option unless it is contraindicated or not tolerated. (3-4)

Common Side Effects of Metformin

Like any other medication, metformin may cause side effects from mild to severe. The common side effects reported in clinical trials by more than 5% of the patients are:

Diarrhea 53.2%
Nausea or vomiting 25.5%
Flatulence 12.1%
Asthenia (weakness or lack of energy) 9.2%
Indigestion 7.1%
Abdominal discomfort 6.4%
Headache 5.7%.

These side effects appear at the beginning of treatment and go away after you take the metformin for a while (3).

Take metformin with food to reduce gastrointestinal side effects. Tell your doctor if the side effects bother you, last for more than a week, come back after they’ve gone away, or start later in therapy. In some cases, your doctor might lower the dose or discontinue the medicine for a short period. (3)

An unpleasant metallic taste may appear in 3 out of every 100 people who take metformin when they start taking medicine. This metallic taste lasts for a short time. (3)

Warning: Lactic acidosis

Lactic acidosis is a rare and serious side effect of metformin due to its accumulation (3,5). This metabolic complication may happen to 0.03 cases per 1,000 patients annually; however, it can be fatal in approximately 50% of the cases (5).

Metformin decreases liver uptake of lactate, which results in increased blood levels of lactate over 5 mcg/mL. Lactic acidosis characteristics are increased blood lactate, decreased blood pH, electrolyte misbalance, and an increased lactate/pyruvate ratio (3, 5).

At the beginning of lactic acidosis, the symptoms that appear are not that specific. The symptoms that could be signs of lactic acidosis are:

feeling cold in hands or feet;
feeling dizzy or lightheaded;
slow or irregular heartbeat;
feeling very weak or tired;
unusual (not normal) muscle pain;
having trouble breathing;
feeling sleepy or drowsy;
stomach pains, nausea, or vomiting.

Call your doctor right away if you have any of the symptoms above. Due to the severity and emergency of this condition, lactic acidosis must be treated in the hospital. (3)

People with diabetes who have renal function impairment, congestive heart failure, or older are at higher risk of lactic acidosis. For these reasons, it is important to tell your doctor if you have any of the following:

severe kidney problems;
liver problems;
drink alcohol very often, or drink a lot of alcohol in short-term;
dehydration (loss of a large amount of body fluids) due to fever, vomiting, or diarrhea, or because of sweating with activity or exercise and do not drink enough fluids;
surgery;
heart attack, severe infection, or stroke.

In some cases, your doctor may temporarily stop your treatment with metformin if you have any of these things. (3)

Vitamin B12 Deficiency During Metformin Treatment

In patients using metformin for a long time, the vitamin B12 body level can decrease below normal, although the levels were normal before metformin treatment. The incidence of vitamin B12 deficiency in clinical trials was 7%, and the good thing is that it is reversible after the treatment I discontinued. (3)

Vitamin B12 is important for the production of red blood cells, DNA, and the functionality of the brain and nerve cells (6). If you have a vitamin B12 deficiency, you might feel very tired, weak in muscles, have a sore and red tongue, have problems with vision, or have yellow skin (7).

People who don’t take sufficient amounts of B12 or calcium are at higher risk. For this reason, your doctor might ask you to check vitamin B12 in your serum while taking metformin. In case of low levels, your doctor may recommend B12 vitamin supplements.

Low Blood Sugar

Although hypoglycemia (blood sugar level below 70 mg/dL) (8) is described as a side effect, metformin therapy does not cause it. It happens if the calorie intake is not regular and sufficient, the exercise and diet are not balanced, drink alcohol, or because of the combination therapy of metformin and other medications. (3)

Insulin and sulfonylureas (glipizide, glimepiride, or glyburide) increase the risk for diabetic hypoglycemia (8).

If the blood sugar level is low, you will feel hungry, shaking, trembling, confused, and sweating, and find it difficult to concentrate (7-8).

You can work on hypoglycemia prevention if you eat regularly, don’t skip breakfast, increase carbohydrate intake with more intensive exercise, and take fast-acting carbohydrates (fruit juice or sweets) if your level gets low (7).

Severe hypoglycemia requires emergency care because it can lead to convulsions or seizures, unconsciousness, or even death, although rarely. In a potentially serious situation, glucagon, a hormone, should be given to ensure sugar in the blood. At the same time, don’t use medications such as insulin. Call 911 if the person with hypoglycemia is not responding or glucagon cannot be given. (8)

Metformin Recalls: Any Reason to Worry for Those Using Metformin

You might have heard or read that some metformin tablets have been recalled in the last couple of years. However, if it concerns you about metformin safety, don’t worry. The reason that some metformin tablets were recalled is due to the presence of N-nitroso dimethylamine above the limits. N-nitroso dimethylamine is a carcinogen substance to human beings; therefore, when found in higher amounts in some products, those metformin tablet batches were recalled. (9-10)

If it happens in the future, your doctor or pharmacist will replace you with another product.

Metformin Interaction with Other Medications

Metformin may interact with some drugs; therefore, always tell your doctor if you take prescription or over-the-counter medicines, supplements, or herbal products.

For instance, furosemide (a diuretic that helps you eliminate fluids from the body) increases the concentration of metformin in the blood. Nifedipine, a medication for high blood pressure treatment, increases metformin absorption (3).

Certain drugs used together with metformin may increase the risk for lactic acidosis:

Drugs that reduce metformin elimination (ranolazine, vandetanib, dolutegravir, and cimetidine) from the body;
Carbonic anhydrase inhibitors (used for glaucoma, congestive heart failure, epilepsy, and other diseases such as topiramate, zonisamide, acetazolamide, or dichlorphenamide). (3)

How to Take Metformin

Metformin dosage depends on its individual effectiveness and tolerance, so there is no fixed dose regime. The therapy always starts with a lower dose and goes step up to find the minimal dose that effectively controls glucose and, at the same time, avoids gastrointestinal side effects (3)

The manufacturer’s recommended metformin starting dose, approved by the FDA, in adults and children is 500 mg. Adults can take it once daily or be divided into two doses, depending on the formulation, while children should take it in divided doses.

Your doctor may increase the dose to 500 mg weekly, up to the maximum recommended daily dose. For adults, the maximal daily dose of metformin is 2,550 mg, and for children, it is 2,000 mg. If the therapeutically effective dose is above 2,000 mg, it will be better tolerated if it is divided into three doses (3).

The extended-release formulation can be prescribed to adults only at a maximal dose of 2,000 mg once daily (3).

Take your metformin tablet with food (3).

Final Thoughts on Metformin Side Effects

Moving to pharmacotherapy for blood sugar control shows that the pre-diabetic condition cannot be managed only with diet and physical activities. Yet, beginning treatment with metformin or other medications cannot be the only way to reach the goal.

Healthy lifestyle behaviors, diabetes self-management, avoidance of clinical inertia, and weight management play an essential part in the overall management of glucose-lowering.

Take your therapy regularly and talk with your doctor if you notice any adverse reactions. You may find all possible side effects in the Patient information (3). In case of an adverse event, report to your doctor and the Food and Drug Administration’s (FDA) MedWatch Adverse Event Reporting program online (https://www.fda.gov/safety/medwatch-fda-safety-information-and-adverse-event-reporting-program) or by phone (1-800-332-1088).

Keeping a normal blood sugar level is a long run but keeps you away from more severe health complications.

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Metformin Side Effects | When and Why is Metformin Used