Metformin: Comprehensive NHS-Aligned Information

Metformin is a biguanide drug. It has been a key treatment for type 2 diabetes since 1958 in the UK. It is one of the most prescribed medicines worldwide.

Over 20 million prescriptions are given in England each year.

Metformin works in three main ways:

1. Reducing hepatic glucose output

The liver normally releases glucose between meals. It does this by making new glucose (gluconeogenesis) and breaking down stored glucose (glycogenolysis). Metformin stops both these processes.

This reduces the amount of glucose in your blood. This is its main effect and causes most of its glucose-lowering action.

2. Improving insulin sensitivity

Metformin helps muscle cells take up glucose better. This happens when insulin is present. Your body can then manage blood glucose more effectively. It does this with the insulin it already makes.

It does not need to produce more.

3. Slowing intestinal glucose absorption

Metformin also slightly reduces how much glucose your gut absorbs. This adds to its overall glucose-lowering effect.

Metformin does not make your body produce more insulin. So, it rarely causes low blood sugar (hypoglycaemia) when used alone. This is safer than other diabetes drugs, like sulphonylureas and insulin.

NICE guideline NG28 suggests metformin as the first drug to try. This applies to all adults newly diagnosed with type 2 diabetes. This is unless there is a clear reason not to use it.

Metformin comes in several forms in the UK. The NHS prescribes all of them generically. They have a very low cost.

Immediate-release (standard) tablets

• Strengths available: 500 mg and 850 mg
• Starting dose: 500 mg once daily with food, usually with the evening meal
• How to increase: Increase by 500 mg every 1 to 2 weeks, if you can tolerate it
• Usual dose: 500 mg to 850 mg two to three times daily
• Maximum dose: 2,000 mg per day. Some guidelines allow 2,550 mg in divided doses.

Modified-release (MR/slow-release) tablets

• Strengths available: 500 mg and 1,000 mg
• Starting dose: 500 mg once daily with the evening meal
• How to increase: Increase by 500 mg every 1 to 2 weeks
• Usual dose: 1,000 mg to 2,000 mg once daily
• Maximum dose: 2,000 mg per day

Modified-release tablets are taken once daily. This is usually with the evening meal. They release the drug slowly over several hours. This lowers peak drug levels in the gut.

It also greatly improves how well your stomach tolerates it. The BNF states that MR forms are good first-line options. This is true if gut side effects are likely.

They are also good if you could not tolerate standard tablets before.

Oral solution

A liquid form is available: 500 mg/5 mL. This is for patients who cannot swallow tablets. It costs more than tablets. It is usually kept for specific medical needs.

Cost

Metformin is very cost-effective. A month's supply of standard 500 mg tablets costs the NHS about 90 pence. This makes it one of the cheapest treatments for long-term conditions.

Regular checks ensure metformin stays safe and effective. The NHS diabetes annual review covers most of these. Some checks may be needed more often.

HbA1c (glycated haemoglobin)

This blood test shows your average blood glucose over the last 2 to 3 months. NICE suggests checking HbA1c every 3 to 6 months. This is when your treatment is changing.

Once stable, check it at least every 6 months. For most type 2 diabetes patients on metformin alone, the target is 48 mmol/mol (6.5%). Or, it may be a personal target agreed with your diabetes team.

Kidney function (eGFR and creatinine)

Your kidney function should be checked before you start metformin. It should then be checked at least once a year. If your eGFR is between 45 and 59, check it every 6 months.

If it is between 30 and 44, check it every 3 months and lower the dose. Stop metformin if your eGFR falls below 30.

Vitamin B12

If you take metformin for more than 3 to 4 years, your B12 levels should be checked. This is especially true if you have symptoms of a deficiency.

These include tiredness, tingling, or large red blood cells. NICE guideline NG28 stresses the need to monitor B12 for long-term metformin users.

Full blood count

An annual FBC can find macrocytic anaemia. This is caused by low B12 or folate. If your mean cell volume (MCV) rises for no clear reason, check B12 and folate levels.

Blood pressure, lipids and weight

These are part of the standard diabetes annual review. They help assess your overall heart risk. Metformin has a neutral or slightly good effect on all three.

Foot checks, eye screening and urine albumin

These are specific diabetes screening tests. They are not specific to metformin. However, they are vital parts of your annual review.

In the UK, metformin is a prescription-only medicine. You cannot buy it without a prescription. Here is how you usually get it.

Diagnosis of type 2 diabetes

Metformin usually starts after a formal diagnosis of type 2 diabetes. This is confirmed by an HbA1c of 48 mmol/mol (6.5%) or higher on two separate tests.

Or, it can be a single result above 48 with symptoms. Your GP will typically make the diagnosis and start treatment.

Initial consultation

Your GP or practice nurse will:

• Confirm the diagnosis with blood tests
• Check your kidney function (eGFR), liver function, and full blood count
• Review your medical history for any reasons not to use metformin
• Discuss changes to your lifestyle, such as diet, exercise, and weight management
• Start metformin at 500 mg once daily. They will arrange a follow-up in 2 to 4 weeks.

Ongoing prescriptions

Once you are stable on metformin, you will get repeat prescriptions. Most GP practices issue these electronically. You can order your medicine through the NHS App.

You can also use an online patient portal or contact the surgery directly.

Prescription costs

Patients with diabetes can get a free medical exemption certificate (medex). This means all your NHS prescriptions are free. This includes all medicines, not just diabetes ones.

Your GP surgery or diabetes nurse can help you apply.

Diabetes education

The NHS offers free structured education programmes. Examples include DESMOND and X-PERT. These programmes cover medicines, diet, exercise, blood glucose checks, and preventing problems.

Ask your GP or diabetes nurse for a referral.

Metformin is almost always the first medicine for type 2 diabetes. But as the condition worsens, more treatments may be needed. These help keep blood glucose under control.

NICE guideline NG28 shows a clear treatment path.

Step 1: Metformin alone

If your HbA1c stays too high after 3 to 6 months, a second drug is added. This is after using the maximum tolerated dose of metformin and making lifestyle changes.

Step 2: Metformin plus a second agent

The main choices are:

• Sulphonylureas (gliclazide): These make your body produce more insulin. They carry a risk of low blood sugar and weight gain.
• SGLT2 inhibitors (dapagliflozin, empagliflozin): These reduce glucose reabsorption in the kidneys. They can lead to weight loss and benefit your heart and kidneys.
• DPP-4 inhibitors (sitagliptin, linagliptin): These boost incretin hormones. They do not affect weight and are usually well tolerated.
• GLP-1 receptor agonists (semaglutide, liraglutide): These are injected medicines. They cause significant weight loss and heart benefits. They are being used earlier in treatment more often.

Step 3: Triple therapy or insulin

If two drugs are not enough, a third oral drug, a GLP-1 agonist, or basal insulin may be added to metformin. Metformin is usually continued with insulin.

This is because it lowers the required insulin dose. It also limits weight gain linked to insulin.

Cardiovascular and renal protection

NICE now recommends SGLT2 inhibitors. This is for patients with existing heart disease or chronic kidney disease. This applies regardless of their HbA1c.

It reflects strong evidence of benefit from trials like EMPA-REG OUTCOME and DAPA-CKD.

Metformin remains the basis of treatment at every stage. It is rarely stopped unless a clear reason not to use it develops.

Metformin does more than just lower glucose. This is why it has been the preferred first-line treatment for over 60 years. This is true even with many newer drugs available.

Cardiovascular protection

The UKPDS trial showed metformin reduced all-cause mortality by 36%. It also cut diabetes-related deaths by 42%. This was in overweight patients with type 2 diabetes, compared to diet alone.

This heart benefit was separate from glucose control. No other oral diabetes drug has matched this in a randomised trial.

Cancer risk reduction

Studies show that using metformin often leads to a 10 to 30% lower risk of several cancers. These include bowel, breast, liver, and pancreatic cancer.

Metformin is thought to activate AMP-activated protein kinase (AMPK). This stops cell growth and spread. Randomised trials are ongoing.

However, the evidence is strong enough to be a possible extra benefit of treatment.

Anti-ageing research

The TAME trial is looking into metformin's ability to delay age-related diseases. This is for people without diabetes. Results are not yet out.

But the trial shows growing scientific interest in metformin's many effects.

Cost-effectiveness

Metformin costs about 1 penny per tablet. It is incredibly cost-effective. It would only need to be slightly helpful to justify its use for health economics. In fact, it provides great clinical value.

Safety track record

Over 60 years of real-world use involves hundreds of millions of patients. This provides safety data that no newer drug can match. Serious side effects are rare and well understood.

This makes metformin one of the most thoroughly known medicines in medical practice.