Metformin Warnings: Important Safety Information

Kidney function is the most important safety point with metformin. The liver does not break the drug down. Instead, your kidneys remove it from the body unchanged.

When your kidneys clear it more slowly, metformin builds up. This raises the risk of lactic acidosis, a rare but sometimes fatal problem where acid builds up in the blood.

The BNF sets clear limits based on your estimated glomerular filtration rate (eGFR), a measure of how well your kidneys filter blood:

• eGFR 60 mL/min or above: you can take the full dose of metformin with no restriction
• eGFR 45 to 59 mL/min: you can keep taking metformin, but your kidney function should be checked every 3 to 6 months and the dose reviewed
• eGFR 30 to 44 mL/min: the most you should take is 1,000 mg a day. Check kidney function every 3 months. Consider stopping if your eGFR is falling
• eGFR below 30 mL/min: you must stop metformin. The risk of build-up and lactic acidosis is too high

Your GP or diabetes nurse should check your eGFR before you start metformin and at least once a year after that. You need more frequent checks if your kidney function is borderline.

The same is true if you have conditions that can affect the kidneys. These include high blood pressure, heart failure or repeated urinary tract infections.

Acute kidney injury (AKI), a sudden drop in kidney function, can happen during any serious illness. It is more likely with dehydration, sepsis or drugs that harm the kidneys.

This is why the sick-day rules matter so much. Stopping metformin for a short time during illness stops it building up while your kidneys may be working less well.

The sick-day rules tell you when to stop metformin for a short time. This stops the drug building up to dangerous levels while you are acutely ill.

NHS England, Diabetes UK and NICE all support these rules.

When to stop metformin temporarily:

• Vomiting or severe diarrhoea that lasts more than a few hours
• High fever (above 38.5 degrees C) with signs of dehydration
• Severe infection that needs antibiotics and bed rest
• Any illness that stops you eating or drinking normally
• Sudden heart failure or marked breathlessness at rest

What to do:

1. Stop taking your metformin tablets
2. Keep checking your blood glucose if you have testing equipment
3. Drink small, frequent sips of water or clear fluids to stay hydrated
4. Contact your GP, diabetes nurse or NHS 111 for advice within 24 hours
5. Restart metformin only when you are eating and drinking normally and feel much better. This is usually 24 to 48 hours after your symptoms settle

Why this matters

During a sudden illness, your kidney function can drop fast. Dehydration and low blood pressure are the main causes. If you keep taking metformin during this time, it can build up.

The body then cannot clear lactate fast enough, which triggers lactic acidosis. This is a medical emergency. About 30 to 50% of people who develop it die from it.

Practical tip

Keep a written copy of the sick-day rules with your medicines or on your fridge door. Some diabetes teams hand out wallet cards or fridge magnets with this information.

Make sure family members know the rules too, in case you are too unwell to manage your own medicines.

Two common situations mean you need to stop metformin for a short time. These are surgery and scans that use iodinated contrast media, a special dye that helps organs show up on the image.

Before surgery

Stop metformin on the day of surgery. If your operation is in the morning, stop it the evening before. There are two reasons.

First, the anaesthetic and the stress of surgery can lower blood flow to the kidneys. Second, you usually fast before surgery and may become dehydrated.

Both of these make metformin more likely to build up.

The BNF advises that you restart metformin only when you are eating and drinking normally and your kidney function is stable. This is usually 48 hours after surgery.

For minor procedures under local anaesthetic, where you can eat and drink straight afterwards, you may not need to stop the drug. Check this with your surgical team.

Before contrast-enhanced imaging

Iodinated contrast media is used in CT scans, angiograms and some other scans. It can cause contrast-induced nephropathy, a short-term drop in kidney function.

If metformin is in your system during this time, it can build up.

Current UK guidelines advise:

• For people with eGFR 30 to 44: stop metformin 48 hours before the scan. Do not restart it until your kidney function has been rechecked 48 hours after the contrast was given
• For people with eGFR 45 or above: you can keep taking metformin, but some departments prefer to stop it on the day of the scan to be safe
• For emergency scans: do not delay the scan for metformin. Stop the drug as soon as you can and check kidney function afterwards

Always tell the radiology department that you take metformin when you book or attend a contrast-enhanced scan.

Drinking alcohol while on metformin needs care. Both work on the same metabolic pathways in the body, so they make each other's risks worse.

Lactic acidosis risk

Alcohol blocks gluconeogenesis in the liver, which is how the liver makes new glucose. This is also the main way metformin works. When both are present, the liver clears lactate much less well.

Heavy drinking or binge drinking on metformin sharply raises the risk of lactic acidosis. The risk is higher still if you are also dehydrated or have poor kidney function.

Hypoglycaemia risk

Alcohol stops the liver making glucose for up to 12 hours after you drink. If you take metformin, this can cause delayed hypoglycaemia, meaning low blood sugar.

The risk is greater if you also take a sulphonylurea or insulin. It often happens during the night or the next morning. Signs include sweating, shaking and confusion.

In severe cases you can lose consciousness.

Vitamin B12 interaction

Long-term alcohol use on its own raises the risk of low vitamin B12 and folate. Metformin also lowers how well the body absorbs B12.

Together, heavy drinkers face a much higher risk of macrocytic anaemia (where red blood cells are too large) and peripheral neuropathy (nerve damage in the hands and feet).

Practical guidance

The BNF advises people on metformin to avoid drinking too much alcohol. In practice:

• Moderate, occasional drinking is usually fine if your kidneys and liver are healthy. Keep within the UK Chief Medical Officers' guideline of 14 units a week, spread across several days
• Avoid binge drinking, which means more than 6 units in one session
• If you have liver disease, even fatty liver, discuss your alcohol limits with your diabetes team
• Never drink alcohol on an empty stomach while taking metformin

Metformin has few drug interactions compared with many other medicines. Even so, you should know about several combinations.

ACE inhibitors and ARBs

These blood-pressure-lowering drugs can lower blood flow to the kidneys. This may raise your metformin levels. The combination is very common in diabetes care and is usually safe.

Still, your eGFR should be checked regularly, especially after a dose change.

Diuretics

Loop diuretics (furosemide) and thiazides can cause dehydration. This makes it harder for the kidneys to clear metformin. Drink enough fluids, especially in hot weather or during illness.

Iodinated contrast agents

As noted above, these can cause acute kidney injury. Manage metformin under your local radiology rules before any contrast scan.

Alcohol

As covered above, alcohol raises the risk of both lactic acidosis and hypoglycaemia.

Corticosteroids

Steroids taken by mouth or injection (prednisolone, dexamethasone) raise blood glucose. This can work against metformin.

If you start a course of steroids, you may need a higher metformin dose or an extra diabetes medicine for a while.

Cimetidine

This H2-receptor antagonist, a type of stomach acid drug, competes with metformin in the kidney. This can raise metformin levels by up to 50%.

At normal cimetidine doses this rarely matters in practice. Even so, other acid-suppressing drugs (ranitidine, PPIs) are preferred where possible.

Dolutegravir

This HIV medicine raises the level of metformin in the blood. The BNF advises a maximum metformin dose of 1,000 mg a day if you take dolutegravir.

Your blood glucose control and kidney function should be watched closely.

Always carry an up-to-date list of your medicines. Show it to every prescriber involved in your care.

The use of metformin in pregnancy and breastfeeding is changing, and the evidence is becoming more positive.

Pregnancy

Metformin crosses the placenta. Even so, large observational studies have not linked it to a higher risk of major birth defects.

NICE guideline NG3 (diabetes in pregnancy) says metformin may be used in pregnancy.

It can be used with insulin or instead of insulin for gestational diabetes, especially when insulin is refused or hard to manage.

In type 2 diabetes, you may keep taking metformin in pregnancy if it controlled your glucose well before you conceived. Many diabetes teams prefer to switch to insulin for tighter control.

The choice should suit you and be made together with your diabetes and obstetric team.

For women with PCOS, metformin is sometimes used in early pregnancy to lower the risk of miscarriage and gestational diabetes. The evidence for this is not clear-cut.

Breastfeeding

Metformin passes into breast milk at very low levels, usually less than 1% of the mother's dose. The BNF states it is compatible with breastfeeding.

The amount the baby takes in is far below any treatment dose. Published studies report no harm to breastfed babies.

Key points

• Do not stop metformin suddenly if you find out you are pregnant. Contact your diabetes team for advice on whether to continue, switch or adjust your treatment
• Blood glucose targets are tighter in pregnancy (fasting below 5.3 mmol/L, 1-hour after meals below 7.8 mmol/L)
• Make sure you take enough folic acid (5 mg a day) before you conceive and during the first trimester if you have diabetes