Biotech

Metformin: Benefits, side effects, dosage and research

Metformin is a medication that has become a cornerstone in the management of Type 2 diabetes, offering significant benefits in blood sugar control.

However, its uses extend beyond diabetes management, encompassing potential benefits for weight management and treating conditions like PCOS.

Yet, as with any medication, metformin comes with its own set of side effects and considerations.

Understanding the benefits, side effects, dosage, and the latest research on metformin is essential for individuals seeking to optimize their health and wellness.

Whether you’re someone living with diabetes, curious about metformin’s role in weight management, or interested in its potential applications beyond blood sugar control, this comprehensive guide aims to provide you with the knowledge you need to make informed decisions about metformin and its place in your health and wellness journey.

What exactly does metformin do?

Patients with type 2 diabetes mellitus are prescribed medications to control their blood glucose or blood sugar levels. Metformin is recognized as the first line of treatment for those newly diagnosed with type 2 diabetes mellitus. 

Metformin is a synthetic drug that was developed in 1922. Its development was guided by knowledge of French lilac as a medicine that could treat sweet urine [1].

French lilac has a scientific name of Galega officinalis and has active components called galegine and quanidine. The active galegine has been shown to have hypoglycemic effects but was found to be too toxic when administered directly to humans [1].

However, two synthetic derivatives of galegine called phenformin and metformin were not poisonous and had the same blood glucose-lowering effects. Metformin and phenformin are biguanadines.  

What are the benefits of metformin?

Unlike most synthetic and modern drugs, metformin is derived from herbal medicine. It was not designed to target a specific disease mechanism or pathway.

Metformin was established to be safe and effective, but until now, this drug’s molecular mechanisms of action are still debated. However, some studies show how metformin acts in the body and how it is metabolized. 

Available in tablet or liquid form, once ingested orally, 70% of immediate-release metformin is absorbed in the body’s small intestine, while the other 30% passes through the colon and is later excreted in the feces [2]. Metformin is also excreted through the kidneys and is intact when released in the urine. 

Metformin offers a range of benefits, making it a crucial medication in managing Type 2 diabetes and other metabolic conditions. Let’s delve into these benefits in more detail:

1. Managing Type 2 diabetes

The primary benefit of metformin is its ability to effectively lower and control blood sugar levels in individuals with Type 2 diabetes [3].

By enhancing insulin sensitivity and reducing liver glucose production, metformin helps keep glucose within a healthy range, preventing hyperglycemia (high blood sugar).

Metformin has also been shown to reduce HbA1c levels, a measure of long-term blood sugar control.

Lower HbA1c values are associated with a reduced risk of diabetes-related complications, such as cardiovascular disease, kidney problems, and nerve damage.

2. Potential weight management

Some individuals may experience reduced appetite and a sense of fullness while taking metformin.

This can lead to lower calorie intake, aiding in weight management efforts. However, the weight loss effect can vary among individuals.

Metformin may lead to modest weight loss in certain individuals. While not a primary weight-loss medication, it can contribute to shedding a few pounds, which can be significant for diabetes management and overall health.

3. Treatment for PCOS

Metformin is often prescribed to women with PCOS to regulate menstrual cycles and improve fertility [4].

It helps reduce insulin resistance, which is common in PCOS and can restore regular ovulation.

PCOS is associated with elevated levels of androgens (male hormones) in women, leading to symptoms like excess facial hair and acne. Metformin can help lower androgen levels, alleviating these symptoms.

Metformin, often used in combination with other treatments, can improve fertility in women with PCOS by addressing insulin resistance and hormonal imbalances.

It’s important to note that while metformin offers significant benefits, individual responses may vary.

Some people may experience greater improvements in blood sugar control or weight loss than others.

Additionally, metformin’s effectiveness can be influenced by factors such as diet, exercise, and genetic predisposition.

Before starting or adjusting metformin treatment, it’s crucial to consult with a healthcare professional who can assess your specific needs, monitor your progress, and tailor the treatment plan.

What is the most common side effect of metformin?

While metformin offers valuable benefits for managing Type 2 diabetes and related conditions, it’s important to be aware of potential side effects and risks associated with its use. 

Metformin is known to have some common and severe side effects. Understanding these considerations is crucial for informed decision-making and safe medication management:

Gastrointestinal distress

Since it is absorbed through the intestine, one common side effect is the gastrointestinal system [5], including symptoms like nausea, diarrhea, and abdominal pain. Some of the stomach problems commonly encountered in patients taking metformin include the following: 

  • Gas 
  • Heartburn 
  • Stomach pain 
  • Diarrhea 
  • Nausea 

Most of these side effects are mild and often go away after a few days of metformin intake. However, when these side effects persist, call your doctor and ask for advice on how to manage or treat these side effects. 

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Long-term side effects

Vitamin B12 deficiency: Prolonged use of metformin has been associated with a higher risk of vitamin B12 deficiency [6]. Vitamin B12 is important for nerve health and overall well-being.

Regular monitoring of B12 levels and supplementation, if necessary, may be recommended for individuals on long-term metformin therapy.

Kidney function concerns: Metformin is primarily excreted through the kidneys. In rare cases, it can cause or exacerbate kidney problems, particularly in individuals with pre-existing kidney issues. Regular monitoring of kidney function is important while on metformin.

Some side effects are more severe and would require you to call your doctor immediately. If you feel any of these symptoms when taking metformin, immediately call your doctor: 

Hypoglycemia (low blood sugar). Symptoms of hypoglycemia include the following: 

  • Fast heart rate
  • Sweating 
  • Dizziness
  • Drowsiness
  • Hunger
  • Feeling jittery or shaking 
  • Headache
  • Confusion 
  • Weakness 

While hypoglycemia is the most common side effect, other side effects warrant an immediate visit to the hospital or a call to your doctor. One of these side effects includes lactic acidosis.

Signs of lactic acidosis can include stomach pains, vomiting, nausea, sleepiness, trouble breathing, weakness, tiredness, unusual muscle pain, slow or irregular heart rate, lightheadedness, and dizziness. 

Individuals taking metformin can also experience low vitamin B12 levels. When patients take higher doses of vitamin B12 over extended periods, this can reduce Vitamin B12 levels [7]. Symptoms of low vitamin B12 include loss of appetite, muscle weakness, low energy, and numbness or tingling in the hands and feet. 

Who should avoid metformin?

Those with kidney impairment

Individuals with severe kidney impairment or end-stage renal disease should avoid metformin, as their kidneys may not effectively clear the medication from the body, increasing the risk of adverse effects.

Liver disorders

Metformin is typically safe for individuals with liver disease, but close monitoring may be necessary as liver function can impact metformin metabolism.

Allergies or sensitivities

If you have a known allergy or sensitivity to metformin or any of its ingredients, you should not take the medication and should discuss alternative options with your healthcare provider.

Pregnancy and breastfeeding

The use of metformin during pregnancy and breastfeeding should be carefully considered in consultation with a healthcare professional, as the risks and benefits may vary depending on individual circumstances.

How much metformin should you take?

An appropriate dosage of metformin is necessary to control hyperglycemia in patients with type 2 diabetes mellitus.

The dosage between adults and children is different for metformin. Further, tablets are available as immediate-release or extended-release tablets. 

In adults, the dosage is as follows [8]: 

  • Immediate-release tablets of metformin: 600 mg, 850 mg, and 1000 mg
  • Extended-release tablets: 500 mg, 750 mg, 1000 mg. 
  • Extended-release oral solution: 500 mg, 750 mg, 1000 mg

Pediatric dosage forms include the following [8]: 

  • Immediate-release tablets: 500 mg, 850 mg, 1000 mg 
  • Extended-release tablets: 500 mg, 750 mg, 1000 mg
  • Oral solution: 500 mg, 750 mg, 1000 mg 

Older adults with type 2 diabetes and impaired kidney function are advised not to take metformin.

Since metformin is excreted through the kidney, poor kidney function could result in an increased concentration of metformin in the blood.

This could have adverse effects since this can lead to hypoglycemia, which requires emergency treatment. 

What is the latest research on metformin?

Metformin is not only used to treat type 2 diabetes. Recent research studies have shown that this drug can lead to a longer life.

Since many people aim for longevity, taking metformin could be an answer to a longer life. 

Longevity, which means extending individuals’ lifespan and health span, may be within reach with metformin. A recent review [9] has shown that metformin can have anti-aging effects.

Although more studies are still needed to verify if metformin can extend lifespan, current evidence from published literature suggests that metformin has the potential to increase longevity. 

Metformin is believed to prolong life by reducing the effects of type 2 diabetes, cardiovascular diseases, cancer, and cognitive decline [9]. Healthspan also increases as people who live longer have better health. 

The protective effects of metformin and its role in longevity may be due to improved cellular metabolism, enhanced insulin sensitivity, anti-hyperglycemic actions, protective effects on vascular and endothelial function, and reduction of oxidative stress [9]. 

Apart from the cardiovascular benefits of metformin, this drug has been shown to benefit specific diseases or conditions. Doctors are currently prescribing metformin as an off-label drug for the following conditions: 

Polycystic ovary syndrome (PCOS)

Metformin has been prescribed as an off-label drug for PCOS since it can regulate menstruation and reduce blood glucose levels and fertility.

PCOS is seen in young women who develop multiple cysts in their ovaries. Symptoms of PCOS include irregular menstruation and fertility problems. 

Weight gain from antipsychotic medications

Metformin has been shown to reduce weight gain in those taking antipsychotic drugs. Individuals with mental illness are prescribed antipsychotics to manage the symptoms of this illness. However, antipsychotics can lead to weight gain. 

Gestational diabetes and prediabetes

Metformin can prevent gestational diabetes in pregnant women at risk of type 2 diabetes. Metformin may also delay the onset of type 2 diabetes mellitus in individuals with high blood glucose levels but not yet enough to qualify for type 2 diabetes. 

An off-label drug is the use of medicine to treat conditions not approved initially as part of its intended use.

For example, metformin is only approved for type 2 diabetes mellitus treatment. It becomes an off-label drug if it is used to treat PCOS. 

Currently, researchers are investigating if metformin can be used as an off-label drug for the following conditions: 

  • Cancer
  • Dementia and stroke 
  • Slow aging, increase lifespan, and prevent age-related disease 

Many people not only want longevity or a longer life, but they also want to have an excellent health span. This means enjoying a disease-free life or having fewer but controlled long-term conditions.

Final takeaways

Metformin’s ability to regulate blood sugar levels, support weight management efforts, and assist in the management of PCOS has made it a cornerstone medication for countless individuals striving for better health and wellness.

However, the use of metformin comes with considerations. Understanding the benefits, potential side effects, and proper dosage guidelines is essential for making informed decisions about its place in your healthcare journey.

Remember that healthcare is a dynamic and evolving field, so staying informed about the latest research and treatment options can empower you to make the best choices for your health and wellness journey.

FAQs

What is the primary function of metformin?

The primary function of metformin is to control blood sugar levels in individuals with Type 2 diabetes by improving insulin sensitivity and reducing liver glucose production.

What is the most common side effect of metformin?

The most common side effect of metformin is gastrointestinal discomfort, which may include symptoms like nausea, diarrhea, and abdominal pain.

Who should avoid taking metformin?

Metformin should be avoided by individuals with severe kidney impairment or end-stage renal disease. It may also not be suitable for those with allergies or sensitivities to the medication.

How should metformin be taken, and what is the recommended dosage?

Metformin is typically taken orally with meals, and the recommended dosage varies based on individual needs. It is usually started at a low dose and gradually increased as tolerated, as determined by a healthcare provider.

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[1] https://wchh.onlinelibrary.wiley.com/doi/full/10.1002/pdi.606 
[2] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5552828/ 
[3] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4214027/ 
[4] https://www.verywellfamily.com/treatment-with-metformin-for-pcos-and-infertility-1960178 
[5] https://www.healthline.com/health/diabetes/metformin-side-effects
[6] https://www.wjgnet.com/1948-9358/full/v14/i5/585.htm 
[7] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6867725/ 
[8] https://www.rxlist.com/consumer_metformin/drugs-condition.htm 
[9] https://pubmed.ncbi.nlm.nih.gov/34421827/

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