Curious about clinical trials for Type 1 diabetes?

Researchers are studying thousands of new treatments and you could be a part of finding a cure while accessing the newest treatments for Type 1 diabetes.

What is metformin?

Metformin¹ is a prescription medication used to treat type 2 diabetes. It is also often used off-label to treat type 1 diabetes.

The medication improves the function of insulin to lower blood glucose levels and reduce insulin resistance.

Metformin should only be used for type 1 diabetes treatment if you are experiencing insulin resistance.

What does metformin do?

Metformin increases your body's sensitivity to insulin, thus increasing the transportation of glucose (sugar) from the blood into cells to be stored and used for energy.

Metformin also reduces insulin resistance, which may occur when undergoing insulin therapy. Additionally, metformin can reduce the glucose released into the bloodstream from the liver, further reducing sugar levels in the blood.

What are the different types of metformin?

Metformin is an oral medication that can be taken in liquid or tablet form. To obtain metformin for diabetes treatment, a prescription is required.

Many different brands make metformin medication. Some you may have heard of include:

  • Fortamet

  • Glumetza

  • Riomet

  • Glucophage

Metformin tablets may be standard-release or slow-release tablets. The main difference between these two types is how quickly metformin acts on the body.

These two types of tablets are compared further in this article. Metformin may also be combined with other diabetes medications in one tablet.

What is type 1 diabetes?

Type 1 diabetes² is a chronic autoimmune disease in which the body cannot produce sufficient amounts of insulin. Insulin is needed to move sugar from the bloodstream into cells. If insufficient amounts of insulin are in the body, sugar accumulates in the blood, causing high blood sugar levels.

In type 1 diabetes, sufficient insulin cannot be produced as the body creates autoantibodies. These antibodies attack the beta cells in the pancreas, which are responsible for the synthesis of insulin.

Unlike type 2 diabetes, type 1 diabetes is not thought to be caused by being overweight or having an unhealthy lifestyle. Instead, type 1 diabetes has a genetic link – it can be passed down from parents and grandparents.

However, not all people with the genetic predisposition for type 1 diabetes will develop this condition.

Type 1 diabetes is much less common than type 2 diabetes. Of all the people in the U.S. that have diabetes, only 5-10% are diagnosed with type 1 diabetes.

Symptoms of type 1 diabetes include:

  • Frequent urination

  • Persistent thirst

  • Stomach pain

  • Shortness of breath

  • Nausea and vomiting

  • Dry mouth

How does metformin help type 1 diabetes?

People with type 1 diabetes cannot produce sufficient amounts of insulin. Because of this, they typically have high blood sugar levels.

High blood sugar levels, also called hyperglycemia, can damage blood vessels and increase the risk of heart attacks, stroke, or kidney disease if left untreated.

Type 1 diabetics typically take insulin treatment to lower their blood sugar levels. Although metformin is primarily used for type 2 diabetes, it can be used ‘off-label’ to help insulin work better in type 1 diabetes treatment.

Additionally, metformin can help reduce insulin resistance, which can occur as a result of insulin therapy. Two studies have shown that metformin is an effective treatment option for assisting insulin in lowering blood sugar levels in type 1 diabetic adolescents³ and young adults⁴.

Benefits of metformin for type 1 diabetes

Reduced risk of complications

Metformin may provide benefits for type 1 diabetes when used in addition to insulin therapy by reducing the risk of complications.

Complications of type 1 diabetes can occur if the condition is not managed effectively and blood sugar levels remain too high. By assisting the functions of insulin, metformin can help ensure blood sugar remains at a healthy level.

Improved vascular smooth muscle function

Vascular smooth muscle is the muscle that makes up the majority of the walls of blood vessels throughout the body. High blood sugar levels may damage blood vessels and, therefore, may not function as well as they should.

A small study⁵ has shown that metformin may improve the function of vascular smooth muscle in children with type 1 diabetes.

Lowered required dose of insulin

As metformin improves the function of insulin, it may lower the amount of insulin required for sufficient reductions in blood sugar levels.

Two small studies have shown that when metformin is administered alongside insulin, less insulin is required for effective condition management in type 1 diabetic children⁶ and adolescents³.

Standard-release vs slow-release tablets

There are two types of metformin tablets: standard-release and slow-release. Standard-release tablets, also known as immediate-release (IR) metformin, act on the body quickly, resulting in faster treatment.

Slow-release tablets, also known as extended-release (XR) metformin, dissolve much slower, requiring tablets to be taken less frequently.

Choosing which type of metformin is right for you can be difficult. This table comparing the two forms may help.

How to take metformin

Metformin should always be taken with food to reduce the risk of an upset stomach. Slow-release metformin should be taken once daily at dinner time. Whereas standard-release metformin should be taken in the morning and evening with food.

You will likely be prescribed a small dose of 500 mg when starting treatment with metformin. Your doctor may slowly increase the amount of metformin you are prescribed until the medication has the desired effect.

The daily dose of metformin should never exceed 2,000 mg for slow-release metformin or 2,550 mg for standard-release metformin.

Does metformin cause side effects?

Metformin can cause some side effects. Most side effects are mild and occur when first starting metformin treatment.

These side effects should resolve within a few days. Some severe side effects of metformin have been reported, although these are rare.

Common side effects

Common side effects of metformin are typically short-lived. These side effects include:

  • Stomach pain

  • Diarrhea

  • Nausea and vomiting

  • Changes in taste

  • Redness, burning, or rashes on the skin

  • Loss of appetite

If these symptoms worsen or do not resolve within a few days of starting metformin treatment, consult with your doctor urgently.

Severe side effects

Although severe side effects of metformin are rare, they can occur. It is important to know what these side effects are and their symptoms to ensure you are using metformin safely.

Lactic acidosis

Lactic acidosis is a very rare side effect of metformin, but it is the most severe and requires emergency treatment.

Metformin-associated lactic acidosis is caused by increased lactate⁶ in the blood. This is due to a decrease in lactate uptake by the liver, which is a result of metformin.

This can cause severe symptoms, including:

  • Aching muscles

  • Abdominal pain

  • Weakness

  • Dizziness

  • Sleepiness or drowsiness

  • Slow or fast heart rate

  • Cold in hands and feet

  • Difficulty breathing

If you experience these symptoms while taking metformin, see a doctor immediately. 

Lactic acidosis is very rare — only 10 in every 100,000 people that take metformin experience this side effect. However, when lactic acidosis develops, it is severe. It has a death rate⁷ of 30-50%.

Some people may be more at risk of developing lactic acidosis than others. Risk factors for developing lactic acidosis include:

  • Liver impairment

  • Kidney impairment

  • Dehydration

  • Age (65 + years)

  • Some medications (discuss this with your doctor if you are concerned)

B12 deficiency

Metformin may interfere with the absorption of vitamin B12, resulting in a vitamin B12 deficiency. Vitamin B12 is required for healthy red blood cells. Anemia may be the result of a vitamin B12 deficiency⁸ in severe cases.

Symptoms of vitamin B12 deficiency include:

  • Mouth ulcers

  • Red and sore tongue

  • Irritability

  • Decline in memory and judgment

  • Pale yellow tinge to the skin

  • Pins and needles   

Vitamin B12 deficiency can be reversed by taking a vitamin B12 supplement. In rare situations, like having severe symptoms of vitamin B12 deficiency, your doctor may recommend stopping metformin treatment. 

Calcium aids in the absorption of vitamin B12 and can reverse vitamin B12 deficiencies. If you do not receive enough vitamin B12 or calcium in your diet, you may be at a higher risk of anemia from metformin use. 

Hypoglycemia

Hypoglycemia, or low blood sugar, may result from metformin when taken alongside other diabetes medications, including insulin. 

This does not mean that metformin cannot be taken with other diabetes medications. In fact, it can be used alongside insulin treatment for type 1 diabetes for those with insulin resistance – it just means you need to monitor your blood sugar levels. 

As metformin aids insulin in transporting sugar from the blood into the cells to reduce blood sugar levels, there is a risk that too much sugar may be removed, resulting in low blood sugar levels. 

Blood sugar levels below 70 mg/dL are too low and may result in the following symptoms: 

  • Vomiting

  • Dizziness and lightheadedness

  • Sweating

  • Numbness of lips or fingers

  • Tiredness

  • Hunger

  • Nausea

  • Stomach pain

  • Abnormally fast or slow heartbeat or palpitations

  • Weakness, shaking, or trembling

  • Headache

  • Lack of concentration

Elderly type 1 diabetics and those with adrenal or pituitary issues are at a higher risk of developing hypoglycemia.

To reduce the risk of developing hypoglycemia, it is important to regularly monitor your blood sugar levels. By regularly checking your blood sugar levels, you can prevent substantial drops or increases from occurring.

If your blood sugar levels have dropped below 70 mg/dL, you may see an improvement after consuming:

  • 3-4 glucose tablets (follow the instructions)

  • Jelly beans (check the label for how many jelly beans will make 15 g of carbs)

  • ½ cup or 4 ounces of soda or juice

It is important to re-check your blood sugar levels 15 minutes after attempting to increase your blood sugar. If your blood sugar levels have not improved, you should seek help from your doctor or emergency services.

Long-term side effects

Most of the long-term effects that have been hypothesized have not been determined to be caused by metformin. 

Dementia

Researchers⁹ have found that there may be a possible link between the use of metformin and the onset of dementia. 

However, some studies have also found that metformin, as well as sulfonylureas¹⁰, may reduce the risk of dementia¹¹ in patients with type 2 diabetes. Sulfonylureas are another group of diabetes medications. 

While these results are mixed, it is difficult to know whether metformin increases the risk of dementia or not. It is also important to note that the risk of developing dementia is more than doubled if you have type 2 diabetes. 

This may be why research has found a potential link between metformin use and dementia, rather than finding dementia is caused by the medication itself. 

Pregnancy

Although many medications are not recommended to be used during pregnancy¹², metformin is thought to be safe. 

Additional research¹³ has found that metformin may even reduce the rate of miscarriage in women with polycystic ovary syndrome (PCOS).

Nerve damage

It has been speculated that metformin may cause nerve damage or neuropathy. Nerve damage may result from a vitamin B12 deficiency and cause nerve pain. 

However, nerve damage is also a side effect of uncontrolled diabetes, and metformin is often used to treat diabetes that cannot be controlled by insulin alone. 

Therefore, it is hard to know whether metformin directly causes nerve damage or not — although it is generally considered not to cause neuropathy.

Anemia

Anemia is a rare but severe side effect of metformin. It may be the result of a vitamin B12 deficiency caused by metformin. If a vitamin B12 deficiency is not treated, it may result in anemia. 

Managing the effects of metformin with type 1 diabetes

You may experience some of the side effects of metformin discussed above. Here are some tips for managing these side effects. 

Start metformin on the weekend

Like many other medications, some common side effects may occur when beginning treatment with metformin. These generally only last a few days. 

If possible, you may want to consider starting metformin treatment on the weekend or when you have some time off work. This would allow you to relax and deal with any side effects in your own time. 

Start with a low dose

When you start metformin treatment, whether for the first time or after a break, your doctor will likely prescribe a low dose of 500 mg per day. This is because the risk of developing uncomfortable side effects is reduced when a dose is smaller. 

Once your body is used to the presence of metformin, the dose may be increased.

Take with food

A common side effect of metformin is abdominal pain or an upset stomach. This could be avoided by taking your metformin with food. 

Metformin treatment doesn’t usually cause low blood sugar when taken on its own unless you don’t eat enough food in general. Metformin might, however, cause low blood sugar if you take other diabetes medications. 

Extended-release tablets

If you are struggling with side effects from the standard-release metformin tablets, you may ask your doctor to prescribe extended-release metformin tablets. 

Because the extended-release tablets dissolve slower, you will probably experience fewer side effects. 

Discuss with your doctor

If the side effects of metformin worsen or do not resolve within a few days, you should consult your doctor. They may be able to adjust your medication. 

Call 911

If you experience any severe side effects of metformin, such as lactic acidosis or hypoglycemia, call 911 or see a doctor immediately. 

These side effects are rare when metformin treatment is managed correctly. However, when they do occur, they may be life-threatening.

Important warnings for metformin with type 1 diabetes

Metformin is contraindicated for (should not be taken by) people who have severe renal (kidney) impairment, known hypersensitivity to metformin, acute or chronic metabolic acidosis, including diabetic ketoacidosis, or hepatic (liver) impairment.

These conditions may increase the risk of developing the severe side effects of metformin.

Lactic acidosis is metformin's most severe side effect and may be life-threatening. Lactic acidosis may result in hypothermia, muscle aches or pain, hypotension, abdominal pain, respiratory distress, or death.

Risk factors for developing lactic acidosis include renal impairment, dehydration, sepsis, hepatic impairment, and being 65 or over.

Other treatments for type 1 diabetes

Insulin treatment

Insulin treatment is essential for type 1 diabetes. For many people with type 1 diabetes, metformin is not required, as insulin treatment alone may be enough to reduce blood sugar levels. Insulin treatment may be in the form of a pen, syringe, or pump.

Insulin pens and syringes inject insulin into the body, past the layer of fat under the skin. These must be administered once, twice, or more daily, depending on the type of insulin used. The needle from a pen or syringe should be changed once a day or after every injection.

Although insulin pens are thought to be more accurate when administering doses below 5 IU, there is no benefit to using the pen over the syringe for larger quantities.

Insulin pumps are small devices that continuously administer doses of insulin throughout the day and night. These pumps mimic the way a healthy pancreas releases insulin.

Artificial pancreas

The first artificial pancreas was approved by the FDA¹⁴ in 2016. These devices continuously monitor glucose levels in the blood and administer varying amounts of insulin as required.

An artificial pancreas differs from an insulin pump as the artificial pancreas adjusts the dose of insulin depending on the current blood sugar levels. An insulin pump provides a constant dose.

Pramlintide

Pramlintide injections may be taken alongside insulin treatment if insulin treatment alone is not sufficient to reduce blood sugar levels after a meal. The risk of developing hypoglycemia is increased when taking pramlintide, so it is crucial that you and those around you are aware of the signs and symptoms of hypoglycemia.

Pancreatic islet transplantation

Pancreatic islet transplantation¹⁵ is currently only available to participants in clinical trials. However, it may be a promising treatment for type 1 diabetes. This treatment involves taking pancreatic islet cells from a healthy donor and placing them in a patient with type 1 diabetes.

Pancreatic islet cell clusters contain beta cells. Beta cells are the cells that produce insulin and are the targets of autoantibodies produced in type 1 diabetics.

By placing healthy beta cells in patients with type 1 diabetes, it is thought that the patient may be able to synthesize some insulin, reducing the amount of treatment required.

The lowdown

Metformin is an anti-diabetic medication primarily used for type 2 diabetes. It is sometimes used to treat type 1 diabetes alongside insulin therapy.

Metformin aids the function of insulin, helping it to clear sugar from the bloodstream and reduce the amount of sugar released from the liver. Insulin resistance can sometimes arise from insulin treatment. Metformin may reduce such resistance.

There are some side effects of metformin use. Most side effects ease after a few days of onset. Other, rarer side effects may be severe and require immediate medical attention.

  1. Metformin and diabetes | Diabetes UK

  2. What is type 1 diabetes? | Centers for Disease Control and Prevention (CDC)

  3. The effect of metformin as an adjunct therapy in adolescents with type 1 diabetes (2017)

  4. Comparison of adjunctive therapy with metformin and acarbose in patients with Type-1 diabetes mellitus (2017)

  5. Effect of metformin on vascular function in children with type 1 diabetes: A 12-month randomized controlled trial (2017)

  6. Glucophage® (metformin hydrochloride) tablets (2017)

  7. Metformin-associated lactic acidosis: Current perspectives on causes and risk (2016)

  8. Glumetza® (2011)

  9. Metformin, other antidiabetic drugs, and risk of Alzheimer's disease: a population-based case-control study (2012)

  10. Incidence of dementia is increased in type 2 diabetes and reduced by the use of sulfonylureas and metformin (2011)

  11. Metformin and the risk of dementia in type 2 diabetes patients (2019)

  12. Metformin in pregnancy: Mechanisms and clinical applications (2018)

  13. Effects of metformin on pregnancy outcomes in women with polycystic ovary syndrome (2016)

  14. FDA approves first automated insulin delivery device for type 1 diabetes | U.S. Food & Drug Administration

  15. Advances in pancreatic islet transplantation sites for the treatment of diabetes (2021)

Other sources:

Curious about clinical trials for Type 1 diabetes?

Researchers are studying thousands of new treatments and you could be a part of finding a cure while accessing the newest treatments for Type 1 diabetes.

Discover which clinical trials you are eligible for

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Have you taken medication for Type 1 diabetes?
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