Metformin is one of the most commonly prescribed medications to treat type 2 diabetes.
Many patients can take metformin, but there are certain instances where it’s contraindicated or not recommended.
In this article, we’ll cover which situations metformin should be avoided, as well as more details about the reason behind the contraindications.
What is metformin?
Metformin is an oral medication used to treat type 2 diabetes. Its common brand names are Glucophage, Glucophage XR, Fortamet, Glumetza, and Riomet.
The United States Food and Drug Administration approved metformin in 1994 to treat type 2 diabetes.
It is in a medication class called biguanides. Biguanides help reduce the amount of sugar your liver makes while improving insulin sensitivity, which helps to reduce high blood sugar.
Metformin doesn’t cause low blood sugar (hypoglycemia), which is one of its benefits. Because it doesn’t cause low blood sugar, you can take metformin along with other medications like sulfonylureas and injectable insulin.
The standard dosage for metformin ranges from 500 milligrams to a maximum of 2,550 milligrams per day. It’s usually recommended to split the dose among meals, typically three times per day.
If the regular version of metformin isn’t well-tolerated, extended-release tablets are recommended to help reduce side effects.
Metformin is approved to treat type 2 diabetes, but it is often used off-label to treat polycystic ovary syndrome (PCOS) as well.
Although it’s not a weight loss medication, metformin isn’t likely to cause weight gain and is more likely to result in a modest amount of weight loss.
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What are the side effects of metformin?
All medications come with potential side effects. The most commonly reported side effects of metformin are considered minor and aren’t life-threatening. However, there is a small risk of developing more serious health issues.
Commonly reported side effects
- Heartburn
- Stomach pain
- Nausea or vomiting
- Bloating
- Gas
- Diarrhea
- Constipation
- Weight loss
- Headache
- Metallic taste in your mouth
Less common but serious potential side effects
The most well-known rare complication of taking metformin is lactic acidosis. Lactic acidosis is a condition where your body produces too much lactic acid.
The symptoms lactic acidosis causes include:
- Abdominal or stomach discomfort
- Decreased appetite
- Diarrhea
- Fast, shallow breathing
- A general feeling of discomfort
- Muscle pain or cramping
- Unusual sleepiness, tiredness, or weakness
Lactic acidosis can be fatal by causing organ failure and shock. However, lactic acidosis is very rare with metformin use and typically only occurs if there is a significant overdose.
For instance, of the few case studies of metformin-related lactic acidosis, at least two were from intentional overdoses.
In addition, a study estimates the prevalence of lactic acidosis from metformin use to be 6.3 cases per 100,000 patient years. (Patient years are calculated as follows: If 15 patients participated in a study on heart attacks for 20 years, the study would have involved 300 patient- years (15 x 20).)
Another study states that “when metformin is used as labeled, the increased risk of lactic acidosis is either zero or so close to zero that it cannot be factored into ordinary clinical decision-making.”
Some types of health conditions are contraindicated for metformin use (more on that next) because they might increase lactic acidosis risk.
For example, severe kidney failure can slow the clearance of metformin from your body and increase the risk of lactic acidosis.
The bottom line: lactic acidosis is a serious and potentially fatal side effect of taking metformin, but fortunately is very rare among people taking metformin as prescribed.
It would take a very large amount of metformin (not just accidentally taking a double dose for a few days, for instance) to increase your risk of lactic acidosis.
Metformin contraindications
Metformin is considered safe for most people, making it a popular first-line drug of choice. There are some contraindications in which metformin shouldn’t be used, though.
Severe renal (kidney) dysfunction
Metformin is entirely cleared (removed) by your body through your kidneys. If you have severe kidney disease, your kidneys don’t filter blood as quickly as they should, which means that metformin could build up in your system and lead to lactic acidosis and other more severe side effects.
Part of the way kidney health is assessed is through the estimated glomerular filtration rate (eGFR), which estimates how much blood the kidneys filter in terms of milliliters per minute. A normal GFR is >60 mL/minute.
If the eGFR is between 30-44 mL/minute, it’s recommended that metformin treatment isn’t initiated.
Metformin use is contraindicated with a GFR of less than 30 mL/minute. This correlates with stage 4 kidney disease.
Metformin is a preferred diabetes medication for many patients with kidney disease, so it’s usually only contraindicated in the late/end stages of kidney disease.
Congestive heart failure (CHF)
According to a 2009 paper, the use of metformin was contraindicated in patients with congestive heart failure.
Newer studies suggest that CHF might not always be a contraindication for metformin, but prescribing providers should “use caution” for CHF patients.
Congestive heart failure is a potentially risky health condition in terms of metformin because, according to a study, it can cause renal dysfunction “in nearly all cases,” which raises the lactic acidosis risk.
If a patient with CHF has good kidney function, they may be a good candidate for metformin – but it all depends on the individual.
Severe “hypersensitivity” or allergy to metformin
Drug allergies are rare but do occur. If you’re allergic to metformin, you might experience symptoms like difficulty breathing, swelling, and a skin rash.
Metformin use is contraindicated if you’ve been diagnosed with a metformin allergy.
Some people experience more disruptive side effects from metformin, such as persistent diarrhea that interferes with their quality of life. In those cases, metformin may be contraindicated due to hypersensitivity.
Acute or chronic metabolic acidosis
Metabolic acidosis is a condition where too much acid builds up in your body, typically due to kidney problems.
Lactic acidosis is a form of metabolic acidosis, so metformin shouldn’t be used if you have acute (short-term/current) or chronic (long-term/consistent) metabolic acidosis.
Impaired hepatic (liver) function
There are a variety of liver abnormalities, such as nonalcoholic fatty liver, liver disease, and liver infections like hepatitis B and C.
Metformin is only contraindicated in advanced liver cirrhosis, which is when liver damage is so severe that it scars the liver.
Liver cirrhosis can increase the risk of lactic acidosis because of arterial hypoxemia or low levels of oxygen in the blood.
Hypoxemia can increase the risk of lactic acidosis, which is why cirrhosis is the only contraindicated liver condition for metformin use.
Who should not take metformin?
Children under the age of ten
The United States Food and Drug Administration has approved metformin for use in children aged 10 and older.
While type 2 diabetes is less common in children, it is being diagnosed in younger kids more often.
If a child under ten is diagnosed with diabetes under the age of 10, it is more likely to be type 1 diabetes, which metformin isn’t meant to treat.
If a child under 10 is diagnosed with type 2 diabetes, metformin may not be recommended due to the minimum age set by the FDA.
People with type 1 diabetes
Type 1 diabetes is a different condition than type 2 diabetes. While there may be some potential benefits of using metformin with type 1 diabetes, it isn’t recommended as a first-line treatment for type 1 diabetes.
Using metformin alone to treat type 1 diabetes, especially shortly after diagnosis, could quicken beta cell destruction and worsen blood sugar control.
Alternatives to metformin
Depending on the patient and their existing health conditions, other diabetes medications may be more suitable than metformin.
Sulfonylureas
Sulfonylureas like glyburide, glipizide, and glimepiride are other popular oral medications for treating type 2 diabetes.
These medications come with a risk of low blood sugar, which is one downside to them compared to metformin. However, sulfonylureas might be better tolerated than metformin for some patients.
Insulin
Injectable insulin can be used for most patients regardless of their health conditions, including those with renal impairment.
Insulin comes with the greatest risk of low blood sugar among the choices for diabetes treatment.
However, the risks for other side effects, like nausea, vomiting, etc., tend to be lower with insulin compared to oral diabetes medications.
Insulin can be used in patients with liver cirrhosis and all stages of kidney disease, including those with end-stage renal disease on dialysis.
Conclusion
Metformin is generally considered safe and well-tolerated for many patients. The main instances where metformin is contraindicated are severe renal impairment, some cases of congestive heart failure, allergies to metformin, and liver cirrhosis.
The main reason for metformin being contraindicated is due to the heightened risk of lactic acidosis, a rare but potentially fatal condition where levels of lactic acid build up in the body.
Some potential alternatives to metformin include sulfonylureas and insulin, which are also widely used among patients with type 2 diabetes.
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