Metformin medication review: uses, benefits, how it works and side effects
Metformin is one of the world's most widely prescribed medications and has been used clinically for more than 60 years. Although best known for treating type-2 diabetes, interest in metformin has expanded dramatically as research investigates its potential role in healthy ageing and longevity.
From Goat’s rue to metformin
Originally derived from Goat’s Rue (Galega officinalis), a medicinal herb traditionally used to relieve symptoms associated with excessive urination, metformin was first introduced into clinical practice in Europe during the 1950s before becoming a cornerstone treatment for type-2 diabetes worldwide.
What is metformin?
Metformin is an oral medication classified as a biguanide and unlike some other diabetes medications, metformin does not appear to cause weight gain or low blood sugar (hypoglycaemia) when used alone, making it a preferred option for many people with diabetes.
What is metformin used for?
Metformin is approved (on-label) for managing type-2 diabetes, in conjunction with lifestyle changes, including dietary modifications and increased physical activity, by improving blood glucose control.
It is also commonly prescribed off-label for conditions such as polyendocrine metabolic ovarian syndrome (PMOS), prediabetes, insulin resistance, weight management in selected individuals, prevention of diabetes in high-risk patients and antipsychotic-induced weight gain. Researchers are also exploring its potential roles in cardiovascular health, cognitive ageing, certain cancers and longevity.
How does metformin work?
Metformin works primarily by reducing excessive glucose production by the liver and improving the body's response to insulin. It also has important effects within the gastrointestinal tract and influences several cellular energy pathways, including AMP-activated protein kinase (AMPK).
Rather than having one single target, metformin appears to work through multiple complementary mechanisms that collectively improve glucose regulation and metabolic health.
Metformin works through several mechanisms to lower blood glucose levels:
Reducing liver glucose production
One of the key actions of metformin is its ability to reduce the amount of glucose produced by the liver. In people with type 2-diabetes, the liver often produces excessive amounts of glucose, even when it isn’t needed. Metformin helps to suppress this overproduction, which in turn lowers blood sugar levels.
Increasing insulin sensitivity
Metformin improves the body’s sensitivity to insulin, meaning that the cells are better able to respond to insulin’s signals. This helps the body use insulin more effectively, allowing glucose to be absorbed from the bloodstream and used by the cells for energy.
Enhancing glucose uptake in muscles
In addition to improving insulin sensitivity, metformin helps muscle cells take up glucose from the blood more efficiently. This reduces the amount of glucose circulating in the bloodstream, helping to keep blood sugar levels within a healthy range.
Slowing intestinal glucose absorption
Metformin also has a mild effect on the intestines, reducing the absorption of glucose from the food we eat. This helps prevent a sharp increase in blood sugar levels after meals so helps to level out insulin release.
Potential side effects
Although metformin is generally well-tolerated, some individuals may experience side effects, particularly when they first begin treatment. Common side effects include:
Gastrointestinal Issues: These may include nausea, diarrhoea, stomach cramps or flatulence. These symptoms often improve over time or with dose adjustments.
Lactic acidosis (rare): A very rare but serious side effect of metformin is lactic acidosis, a condition where lactic acid builds up in the blood. This can occur in people with kidney problems or other conditions that affect the kidneys. People taking metformin are typically monitored for kidney function to minimise this risk.
Vitamin B12 deficiency and metformin
Long-term metformin use can reduce the absorption of vitamin B12 and, over time, may lead to low B12 levels or deficiency. The mechanism appears to be multifactorial and may include changes in intestinal motility and reduced uptake of the vitamin B12–intrinsic factor complex in the small intestine. The risk increases with higher metformin doses, longer duration of treatment and other existing risk factors for B12 deficiency.
Vitamin B12 is essential for healthy red blood cell production, DNA synthesis and normal nervous system function. Deficiency may cause fatigue, weakness, anaemia, a sore or inflamed tongue, pins and needles, numbness, cognitive changes or peripheral neuropathy. This is particularly important in people with diabetes because symptoms of B12 deficiency-related neuropathy can potentially be mistaken for diabetic neuropathy.
Conclusion
Metformin is a cornerstone of type-2 diabetes medical management due to its effectiveness in lowering blood glucose levels, improving insulin sensitivity and providing evidence of cardiovascular benefit in some people with type 2 diabetes. It is a relatively safe and affordable medication, with a low risk of hypoglycaemia and modest weight loss benefits.
While metformin is not suitable for everyone, it remains the most commonly prescribed medication for type-2 diabetes and continues to be an important tool in the fight against the global diabetes epidemic. Regular monitoring and a holistic approach to lifestyle changes, including diet and exercise, are crucial for maximising the benefits of those taking metformin.
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