Metformin is one of the most commonly prescribed medications for type 2 diabetes. It helps lower blood sugar levels by improving the way the body handles insulin. While metformin is generally considered safe, it does come with some potential side effects and risks that are important to be aware of. In this article, we will explore the dangers and risks associated with taking metformin so diabetes patients can make informed decisions about their treatment options.
What is Metformin?
Metformin belongs to a class of medications called biguanides. It works by reducing the amount of glucose released by the liver and making muscle tissue more sensitive to insulin to allow better uptake of blood sugar. By doing this, metformin helps lower A1C levels (a key measurement of average blood sugar over 2-3 months) and improves other markers of diabetes control.
Metformin has been used since the 1950s to treat diabetes and is one of the most widely prescribed medications for type 2 diabetes globally. It is often recommended as a first-line treatment for type 2 diabetes, especially in overweight patients. Metformin can be used alone or combined with other medications such as insulin, sulfonylureas, or newer diabetes drugs to improve blood sugar control.
Some key facts about metformin:
– Used along with diet and exercise to improve blood sugar control in type 2 diabetes
– Available as tablet, extended-release tablet, and liquid
– Often the first medication prescribed for type 2 diabetes
– May also be used in women with polycystic ovary syndrome (PCOS)
– Typically taken 1-3 times per day with meals
– Comes in different strengths from 500mg to 1000mg
While it has a good safety profile compared to some other diabetes medications, metformin use does come with some potential side effects and risks.
What are the potential dangers and side effects of metformin use?
Some of the key potential dangers and side effects of metformin use include:
1. Lactic Acidosis
One of the most serious potential risks with metformin use is the development of lactic acidosis. Lactic acidosis is a rare but potentially fatal condition caused by a buildup of lactic acid in the bloodstream.
Lactic acidosis associated with metformin use is very rare, occurring in less than 3 cases per 100,000 patient-years of metformin use. However, it can be fatal in 30-50% of cases.
Lactic acidosis occurs due to metformin accumulating in the body. It is more likely to happen in patients with impaired kidney function due to reduced metformin clearance. Dehydration, low blood oxygen (hypoxia), liver disease, excessive alcohol use, and heart conditions like congestive heart failure can also increase the risk of metformin-associated lactic acidosis.
Symptoms of lactic acidosis include:
– Nausea, vomiting, diarrhea
– Abdominal pain, general body discomfort
– Muscle cramps, weakness, fatigue
– Cool, clammy skin
– Rapid, shallow breathing
– Dizziness, lightheadedness
– Fast or irregular heartbeat
Lactic acidosis is a medical emergency requiring immediate treatment. Metformin use must be stopped immediately at the first signs of lactic acidosis.
2. Vitamin B12 Deficiency
Long-term use of metformin may cause vitamin B12 deficiency in some patients. Vitamin B12 helps form red blood cells and maintain healthy nerve function.
Metformin may interfere with calcium-dependent absorption of the vitamin in the gut. The risk of B12 deficiency increases with metformin use over time and higher doses.
Symptoms of vitamin B12 deficiency include:
– Fatigue, weakness
– Constipation, diarrhea
– Loss of appetite, weight loss
– Numbness or tingling in hands and feet
– Difficulty walking or moving
– Memory loss or confusion
– Depression, mood changes
Severe and prolonged vitamin B12 deficiency can lead to anemia and irreversible nerve damage. Regular monitoring of vitamin B12 levels is recommended for patients on long-term metformin therapy. Vitamin B12 supplements or injections may be needed to correct a deficiency.
3. Gastrointestinal Side Effects
Up to 30% of patients taking metformin experience common gastrointestinal side effects like:
– Nausea, vomiting
– Diarrhea
– Abdominal cramps, discomfort
– Loss of appetite
– Metallic taste in mouth
These metformin side effects are generally mild and tend to improve over time. Taking the medication with food can help minimize GI discomfort. Slowly increasing metformin dosage can also help reduce GI side effects.
More serious GI complications like pancreatitis and bowel ischemia have been reported but are extremely rare. Patients should notify their doctor if severe abdominal pain develops while on metformin.
4. Decreased Vitamin B9 (Folate) Absorption
Metformin may impair the absorption of vitamin B9 (also called folate or folic acid) in some patients, leading to folate deficiency. Folate helps make red and white blood cells and is important for cell growth.
Folate deficiency can result in certain anemias and elevated homocysteine levels, increasing heart disease risk. Women who could become pregnant should take folic acid supplements while on metformin to reduce the risk of fetal neural tube defects.
Doctors may monitor folate levels and prescribe folic acid supplements if long-term metformin use depletes folate stores. Dietary sources high in folate can also help maintain healthy folate status.
5. Low Blood Sugar (Hypoglycemia)
When used as a single therapy, metformin does not directly cause blood sugar levels to get dangerously low as it does not increase insulin production. However, it may increase the risk of hypoglycemia when combined with other diabetes medications that do raise insulin levels, like sulfonylureas or insulin.
Signs and symptoms of low blood sugar may include:
– Shakiness, anxiety, nervousness
– Sweating, chills
– Irritability, mood changes
– Confusion, weakness
– Fast heartbeat
– Lightheadedness, dizziness
– Hunger, nausea
Patients on metformin plus other glucose-lowering medications should monitor blood sugar levels closely to help avoid hypoglycemia episodes.
6. Decreased Absorption of Thyroid Hormones
Levothyroxine is a medication used to treat hypothyroidism (underactive thyroid). Metformin may impair absorption of levothyroxine in some cases. This can lead to worsening hypothyroid symptoms.
Patients on both metformin and levothyroxine should have thyroid hormone levels monitored periodically. Levothyroxine doses may need to be adjusted to account for decreased absorption. Taking the two medications at least 4 hours apart can help prevent interactions.
7. Mitochondrial Toxicity
There is some evidence from animal and cell-based studies that metformin may inhibit a key mitochondrial enzyme involved in cellular energy production called mitochondrial glycerophosphate dehydrogenase.
Disruption of this enzyme may promote the development of muscle cramps and weakness in some patients taking metformin. It can also theoretically increase the risk of lactic acid buildup.
However, the clinical relevance of metformin-related mitochondrial toxicity is still under study. More research is needed to conclusively determine if metformin directly damages mitochondria in humans.
8. Kidney Dysfunction
Metformin is eliminated from the body by the kidneys. Reduced kidney function decreases metformin clearance and raises the risk of lactic acidosis.
Kidney impairment is a contraindication for metformin therapy. Regular monitoring of kidney function is essential while taking this medication.
Metformin may also increase the risk of acute kidney injury in certain situations like dehydration, surgery, infections, or use of IV contrast dye. Patients should stop taking metformin before major procedures or use of contrast agents.
9. Medication Interactions
A number of medications may interact with metformin to increase the risk of side effects or toxicity:
– Diuretics like furosemide can cause volume depletion and impair kidney function.
– NSAIDs like ibuprofen can reduce kidney function and raise metformin levels.
– Certain antibiotics like ciprofloxacin and tetracycline may displace metformin from plasma proteins, raising free drug levels.
– Proton pump inhibitors like omeprazole can decrease metformin elimination.
– Cationic medications like amiloride, digoxin and morphine compete with metformin for renal tubular transport and increase its accumulation.
Doctors should closely review all medications and supplements a patient is taking before prescribing metformin. Metformin dosage may need adjusting if new medications that interact with it are started.
Who Should Not Take Metformin?
Certain conditions may restrict or preclude the use of metformin due to increased risk of side effects:
– Kidney disease or impairment – contraindicated if eGFR is <30 ml/min - Liver disease - contraindicated if liver enzymes 2-3x upper normal limit - Heart failure requiring pharmacological treatment - Chronic hypoxemia, severe lung disease - History of lactic acidosis - Metabolic acidosis - Chronic alcohol abuse, alcoholism - Dehydration or hypovolemia Metformin should not be used in patients undergoing radiologic studies involving IV iodinated contrast agents due to the high risk of developing acute kidney injury. Metformin may be temporarily stopped before surgery and scanned procedures requiring contrast.
Precautions for Safe Metformin Use
The following precautions can help minimize the risks from metformin therapy:
– Start at a low dose of 500mg daily and slowly increase based on tolerance.
– Take with meals to reduce GI side effects.
– Maintain adequate hydration and avoid excessive alcohol intake.
– Temporarily stop metformin before major surgery, scans requiring contrast dye, or long periods of restricted food intake.
– Monitor kidney function regularly, especially in older adults.
– Periodically check vitamin B12, folic acid and thyroid hormone levels.
– Review all new medications for potential metformin interactions.
– Educate patients on signs and symptoms of lactic acidosis and when to seek emergency care.
– Instruct patients to stop metformin and call their doctor if they experience severe GI symptoms, fever, vomiting, severe muscle aches, rapid breathing or heart rate.
Conclusion
Metformin is generally well tolerated and safe when used appropriately under medical supervision. However, it can increase the risk of some potentially serious adverse effects like lactic acidosis, vitamin deficiencies and hypoglycemia when combined with other diabetes medications.
Patients taking metformin should be aware of potential side effects and drug interactions. Healthcare providers can minimize the risks by carefully selecting patients, initiating at low doses, monitoring kidney function, avoiding interactions with certain drugs, and educating patients on warning signs of lactic acidosis.
With responsible prescribing and monitoring by doctors, and adherence to dosage instructions by patients, metformin remains one of the most beneficial first line medications for managing type 2 diabetes. But patients should not hesitate to seek medical attention if they experience any concerning symptoms while taking this medication.