RECALL OF METFORMIN EXTENDED RELEASEIn May 2020, the
Food and Drug Administration (FDA) recommended that some makers of metformin extended release remove some of their tablets from the U.S. market. This is because an unacceptable level of a probable carcinogen (cancer-causing agent) was found in some extended-release metformin tablets. If you currently take this drug, call your healthcare provider. They will advise whether you should continue to take your medication or if you need a new prescription.
Metformin is a medication people with type 2 diabetes take to control blood sugar levels. Although most people tolerate metformin well, some experience side effects including diarrhea, nausea, and vomiting.
This article describes how to monitor and manage any side effects of metformin, whether they occur in the short or long term. We also discuss possible drug interactions.
This section outlines the various uses of metformin and the different types and brand names of the drug.
Uses
Metformin helps control blood sugar levels. It is a
Doctors may also prescribe metformin for people taking antipsychotic medications. These medications can lower insulin resistance and cause people to gain weight. Metformin helps to counteract these side effects.
Metformin may also help treat fertility issues in women with polycystic ovary syndrome (PCOS). However, this is an
Forms
Doctors may prescribe either immediate- or extended-release metformin tablets. Extended-release pills deliver metformin into the bloodstream more slowly and steadily than immediate-release pills.
A person takes extended-release tablets less often throughout the day, but these pills take longer to be effective.
Combination metformin medications are another option. They contain metformin and another antidiabetic medication.
The following table lists the various brand names of metformin and combination metformin medications. The available strengths of each drug are noted in milligrams (mg).
| Metformin-containing drugs | Strengths |
| Glucophage | 500 mg, 850 mg, 1,000 mg |
| Glucophage XR | 500 mg, 750 mg |
| Glumetza | 500 mg, 1,000 mg |
| Combination metformin drugs | Strengths |
| Actoplus Met (metformin and pioglitazone) | 500 mg/15 mg, 850mg/15 mg |
| Actoplus Met XR (metformin and pioglitazone) | 1000 mg /15 mg, 1000 mg/30 mg |
| Avandamet (metformin and rosiglitazone) | 500 mg/2 mg, 500 mg/4 mg, 1000 mg/2 mg, 1000 mg/4 mg |
| Glucovance (metformin and glyburide) | 250 mg/1.25 mg, 500 mg/2.5 mg, 500 mg/5 mg |
| Invokamet (metformin and canagliflozin) | 500 mg/50 mg, 1000 mg/50 mg, 500 mg/150 mg, 1000 mg/150 mg |
| Invokamet XR (metformin and canagliflozin) | 500 mg/50 mg, 1000 mg/50 mg, 500 mg/150 mg, 1000 mg/150 mg |
| Janumet (metformin and sitagliptin) | 500 mg/50 mg, 1000 mg/50 mg |
| Janumet XR (metformin and sitagliptin) | 1000 mg/100 mg, 500 mg/50 mg, 1000 mg/50 mg |
| Jentadueto (metformin and linagliptin) | 500 mg/2.5 mg, 850 mg/2.5 mg, 1000 mg/2.5 mg |
| Jentadueto XR (metformin and linagliptin) | 1000 mg/5 mg, 1000 mg/2.5 mg |
| Kazano (metformin and alogliptin) | 500 mg/12.5 mg, 1000 mg/12.5 mg |
| Kombiglyze XR (metformin and saxagliptin) | 500 mg/5 mg, 1000 mg/5 mg, 1000 mg/2.5 mg |
| Prandimet (metformin and repaglinide) | 500 mg/1 mg, 500 mg/2 mg |
| Segluromet (metformin and ertugliflozin) | 500 mg/2.5 mg, 1000 mg/2.5 mg, 500 mg/7.5 mg, 1000 mg/7.5 mg |
| Synjardy (metformin and empagliflozin) | 500 mg/5 mg, 1000 mg/5 mg, 500 mg/12.5 mg, 1000 mg/12.5 mg |
| Synjardy XR (metformin and empagliflozin) | 1000 mg/5 mg, 1000 mg/10 mg, 1000 mg/12.5 mg, 1000 mg/25 mg |
| Xigduo XR (metformin and dapagliflozin) | 1000 mg/2.5 mg, 500 mg/5 mg, 1000 mg/5 mg, 500 mg/10 mg, 1000 mg/10 mg |
Most people who take metformin tolerate the drug well. However, about
Doctors usually prescribe a low dosage of metformin to people taking the drug for the first time. If necessary, the doctor will increase the dosage, but this will be gradual to prevent side effects.
Taking metformin with meals can help prevent or limit gastrointestinal effects.
Other side effects of metformin can include:
- a runny nose
- low blood sugar
- excessive sweating
- chest discomfort
- headache
- weakness
In rare cases, metformin can cause lactic acidosis, a serious side effect. Lactic acidosis is the harmful buildup of lactic acid in the blood. It can lead to low blood pressure, a rapid heart rate, and even death.
Vomiting and dehydration increase the risk of lactic acidosis in people taking metformin. A doctor may recommend temporarily stopping the medication until vomiting subsides.
The following factors can also increase the risk of lactic acidosis:
- surgery
- low oxygen levels
- alcohol use disorder
- liver failure
- kidney failure
- advanced age
People who are taking metformin should avoid consuming excessive amounts of alcohol. The combination of metformin and alcohol can increase the risk of lactic acidosis.
Many people on metformin need to take the drug for an extended period. Certain side effects can occur only with long term use.
Metformin may affect the absorption of vitamin B-12. Doctors will monitor B-12 levels in people who have been taking metformin for more than 4 months.
The following factors can increase a person’s risk of developing a vitamin B-12 deficiency:
- low vitamin B-12 levels at the start of treatment
- low levels of calcium in the diet
- low absorption of calcium
People with vitamin B-12 deficiency have an increased risk of anemia, as well as certain neurological and psychological symptoms. The severity of these symptoms can range from mild fatigue to severe neurological impairment.
Some symptoms of vitamin B-12 deficiency include:
- changes in skin color
- inflammation of the tongue
- decreased reflexes
- irritability
- decreased sense of smell
- nerve damage
- difficulty walking
- dementia-like symptoms
People who are taking metformin will receive yearly blood tests to monitor for anemia. Doctors will also check for vitamin B-12 deficiency every 2–3 years.
Metformin is not suitable for people with severe kidney or liver failure. A doctor will check a person’s kidney and liver function before prescribing metformin.
Metformin is also not safe for people who have the following conditions:
- an allergy to metformin
- alcohol addiction
- severe infection
- heart failure
- severe circulatory problems
- severe breathing difficulties
People who are about to undergo an X-ray, MRI, or CT scan should tell the radiologist if they are taking metformin. Sometimes, these procedures involve iodinated contrast agents. When combined with metformin, these agents increase the risk of lactic acidosis.
A doctor may also recommend stopping metformin treatment a few days before surgery. General anesthesia can hide low blood sugar levels, and this puts people at risk of hypoglycemia.
The following table shows how metformin interacts with other drugs and how people can manage these interactions.
| Interacting medication | Description | Management |
| Diuretics Corticosteroids Thyroid medications Estrogen and combined oral contraceptives Phenytoin Calcium channel blockers | Combining these drugs with metformin may affect blood sugar control. | A person may need to check their blood sugar levels more frequently. They should notify their doctor of any spikes or dips in these levels. |
| Insulin | Combining insulin and metformin may affect blood sugar control. | A person may need to check their blood sugar levels more frequently. They should notify their doctor of any spikes or dips in these levels. The doctor will adjust the insulin dosage. |
| Alcohol | Drinking excessive amounts of alcohol while taking metformin increases the risk of lactic acidosis. | People taking metformin should avoid excessive alcohol intake. |
| Cimetidine Ranolazine Vandetanib Dolutegravir | These drugs reduce the kidneys’ ability to remove metformin from the blood. This can lead to lactic acidosis. | The doctor should weigh the benefits and risks of recommending these drug combinations. A safer option may be available. |
| Carbonic anhydrase inhibitors (CAIs), such as topiramate or acetazolamide | Anyone taking a CAI and metformin may have an increased risk of lactic acidosis. | Doctors may regularly monitor people taking CAIs and metformin. This will help detect early signs of lactic acidosis. |
Talk to a doctor about any issues that could be side effects of metformin. The doctor may adjust the dosage or suggest an alternate medication.
One study suggests that people may experience less diarrhea when they switch from immediate-release to extended-release tablets.
Doctors will routinely check for signs of vitamin B-12 deficiency and anemia in people who have been taking metformin for more than a few months. Vitamin B-12 and iron supplements may help counteract these issues if they arise in people who need to continue taking metformin.
Metformin is a first-line treatment for type 2 diabetes, and it may alleviate some side effects of antipsychotic medications.
Most people tolerate metformin well, but some experience gastrointestinal issues when starting the treatment.
Increasing the dosage gradually can help prevent side effects. However, some people are unable to tolerate even low dosages of metformin. If this happens, the doctor may recommend switching to an alternate medication.
People who take metformin for an extended period have a risk of vitamin B-12 deficiency and anemia. The doctor will perform regular blood tests to check for these conditions, and they may recommend supplements, if necessary.