Metformin

What Does Metformin Do?

Metformin is a very commonly prescribed drug to treat early/low levels of type 2 diabetes. It works by reducing glucose production in the liver and enhancing insulin sensitivity, thus controlling blood sugar levels. 

Metformin’s off-label use extends to treating polycystic ovary syndrome, gestational diabetes, and preventing type 2 diabetes in individuals at high risk. 

How Does Metformin Work? (the complicated stuff..)

Metformin operates by inhibiting mitochondrial complex I, consequently reducing hepatic glucose production and resulting in decreased fasting and postprandial glucose levels. It also increases peripheral glucose uptake and utilisation, and boosts insulin sensitivity while reducing fatty acid oxidation. Moreover, Metformin activates AMP-activated protein kinase (AMPK), crucial for regulating energy metabolism and possessing anti-inflammatory effects.

Drug Type and Category of Metformin

Metformin is classed as a biguanide antihyperglycemic agent - it is an antidiabetic medication. 

What dosage of Metformin should you be taking?

NICE Guidelines ¹

The dosage of metformin for adults with type 2 diabetes should be initiated as follows:

• Immediate-release metformin: Initial dose is 500 mg orally twice a day or 850 mg orally once a day. The dose can be increased in 500 mg increments weekly or 850 mg every 2 weeks as tolerated, up to a maximum dose of 2550 mg per day. ³
• Extended-release metformin: Initial dose is 500 to 1000 mg orally once a day. The dose can be increased in 500 mg increments weekly as tolerated, up to a maximum dose of 2000 mg per day. ³

Additionally, NICE recommends that the dose of metformin should be stepped up gradually over weeks to minimise the risk of gastrointestinal side effects. ²

What are the side-effects of Metformin?

While it is generally well-tolerated, it can cause some side effects:

Common Side Effects

• Digestive issues: Nausea, vomiting, diarrhea, bloating, gas, constipation, abdominal discomfort
• Headache
• Metallic taste in the mouth
• Decreased appetite
• Weight loss

Taking metformin with food and starting with a low dose can help minimise these side effects, which often improve over time.

Rare but Serious Side Effects

• Lactic acidosis: A rare but serious condition caused by a buildup of lactic acid. Symptoms include abdominal pain, nausea, vomiting, difficulty breathing, and feeling very tired or weak. It is more likely in those with kidney, liver, or heart problems.
• Vitamin B12 deficiency: Long-term use of metformin may lead to low vitamin B12 levels, which can cause anemia and nerve problems. Regular monitoring is recommended.
• Hypoglycemia (low blood sugar): More likely when combined with other diabetes medications. Symptoms include confusion, dizziness, and sweating.

Certain factors can increase the risk of side effects, such as kidney disease, heavy alcohol use, dehydration, and some other medications. Patients should discuss their medical history with their doctor before starting metformin.

Drug Interactions

• Steroid tablets like prednisolone can affect how metformin works, potentially requiring more frequent blood sugar checks and dose changes.
• Diuretics (water pills) such as furosemide may interact with metformin.
• Medicines for heart problems and high blood pressure can interact with metformin.
• Male and female hormones like testosterone, estrogen or progesterone may interact with metformin.
• Other diabetes medications, especially insulin and drugs that increase insulin levels, can interact with metformin.
• Alcohol can increase the risk of a serious side effect called lactic acidosis when taking metformin.
• Certain antibiotics like trimethoprim may increase metformin levels.
• Medications that reduce vitamin B12 absorption like proton pump inhibitors may require monitoring of B12 levels with long-term metformin use.

Natural Alternatives to Metformin

Berberine

Berberine is a plant compound found in herbs like goldenseal, Oregon grape, and barberry. It has been shown to have similar effects as metformin in lowering blood glucose levels and improving insulin sensitivity, but with fewer side effects. ^4,5 Berberine can also help with other conditions like cardiovascular disease, Alzheimer's, and cancer. ⁴

N-Acetyl Cysteine (NAC)

NAC is an amino acid that is crucial for producing glutathione, a powerful antioxidant. In women with PCOS, NAC was found to be superior to metformin in improving cholesterol, fasting blood sugar, and insulin levels. NAC improves insulin sensitivity and protects the body from cellular damage. ⁵

Inositol

Inositol is a vitamin-like substance that has been shown to improve insulin sensitivity and ovulation in women with PCOS. ⁷ It can be easily added to meals.

Cinnamon

Cinnamon has been shown to have antioxidant properties and may help improve insulin sensitivity and lower blood sugar levels. ^6,7 It is a simple spice that can be added to food.

Curcumin

Curcumin is the active compound in turmeric that has potent anti-inflammatory and antioxidant effects. It may help improve insulin sensitivity and lower blood sugar levels. ⁷

Other natural alternatives include chromium, which helps insulin work better, and okra, leafy greens, and broccoli which have beneficial effects. ⁶

Key point you need to know:

Type 2 diabetes is preventable, in most cases. It requires reducing your sugar levels in your diet. Most people can do this. OK, this is going to sound blunt. Cut out biscuits, cake, reduce alcohol (very sugary), stop drinking fizzy drinks, don’t add sugar to your tea or coffee, reduce sugary breakfasts, reduce chocolate, and reduce bread to one slice per day maximum. Re-test your blood sugar levels (HbA1c) at your GP surgery and see if things have improved. It’s a much better option than going on metformin. 

Interesting facts about Metformin

Metformin has a rich history dating back to the early 20th century. Interestingly, the origins of metformin can be traced back to Galega officinalis, a plant that was used in medieval Europe. The active compound, guanidine, was isolated in the 1920s and eventually led to the development of metformin in its current form.

First described in scientific literature in 1922, the drug was introduced as a medication in France in 1957 and has since been used safely for decades, with extensive data on its long-term safety profile. Unlike many other diabetes medications, metformin is unlikely to cause weight gain and may even promote modest weight loss, making it a particularly attractive option for patients.

Ongoing research continues to explore the potential of metformin beyond its traditional use in diabetes management. Researchers are investigating its potential in cancer prevention, neurodegenerative diseases like Alzheimer's, and even in combating the effects of aging, further expanding the versatility and significance of this well-established medication.

Disclaimer

This article is generated for informational purposes only. It was created in September 2024. Medications and medical guidance can change over time. Therefore, it is essential to consult with your general practitioner or healthcare provider before making any decisions regarding medications or treatment plans. Your GP can provide personalised advice based on your specific health needs and conditions.

References

1. https://www.nice.org.uk/cks-uk-only
2. https://gpnotebook.com/pages/diabetes-and-endocrinology/nice-guidance-metformin-in-type-2-diabetes
3. https://www.drugs.com/dosage/metformin.html
4. https://warnerorthopedics.com/is-berberine-a-safe-alternative-to-metformin/
5. https://www.drbrianlum.com/post/natural-alternatives-to-metformin
6. https://www.webmd.com/diabetes/natural-remedies-type-2-diabetes
7. https://www.bensnaturalhealth.com/blog/diabetes-health/natural-metformin/