Is Metformin safe?
Metformin
Metformin (Glucophage) has been the first medicine for type 2 diabetes for decades because it works and serious harm is rare. Stomach upset is the usual problem. Its boxed warning on lactic acidosis is mainly a concern in severe kidney disease, serious illness and heavy drinking.
- Brands
- Glucophage, Glumetza, Fortamet, Riomet; also in many combination pills (Janumet, Synjardy)
- Max daily dose (US label)
- 2,550 mg (immediate release); 2,000 mg (extended release)
- Boxed warning
- Lactic acidosis
- Lactic acidosis
- About 3 to 10 per 100,000 patient-years, similar to diabetes without metformin
- Diarrhoea in US trial
- 53% vs 12% on placebo; 6% stopped because of it
- Kidney limit
- ContraindicationA situation in which a medicine should not be used, because the risk clearly outweighs any benefit, such as a known allergy to it.More in the glossary when eGFR is below 30
- On the market
- UK since 1958, US since 1995
How the score breaks down
The overall score is the weighted average of these factors. Scoring rules
Serious side effects30% of score
82 out of 100, GoodSerious harm is rare. Lactic acidosis occurs at about 3 to 10 per 100,000 patient-years, close to the rate in diabetes generally. The label reports low vitamin B12 in about 7% of patients in 29-week trials. Diarrhoea and nausea are very common but not dangerous.
Overdose margin20% of score
70 out of 100, GoodNormal doses do not cause low blood sugar on their own. Large overdoses are a different matter, with lactic acidosis in about 32% of overdose cases on the label, sometimes fatal and treated with dialysis.
Interactions15% of score
78 out of 100, GoodHeavy drinking, iodinated contrast dye, topiramate and drugs that slow metformin clearance (such as dolutegravir, ranolazine, cimetidine) raise lactic acidosis risk. Insulin or sulfonylureas add the risk of low blood sugar.
Dependence and misuse15% of score
98 out of 100, ExcellentNo dependence, misuse potential or withdrawal. Not a Controlled substanceA medicine or drug that the law restricts because it can be misused or cause dependence. Countries group them into schedules or classes.More in the glossary.
Regulatory warnings10% of score
50 out of 100, WeakBoxed warningThe strongest safety warning the US FDA puts on a medicine's label, printed inside a black border at the top.More in the glossary for lactic acidosis, although the FDA relaxed kidney limits in 2016 as evidence showed it rare. In 2020 the FDA asked several makers to recall extended-release tablets over NDMA impurity above the accepted limit.
Track record10% of score
95 out of 100, ExcellentUsed in Europe since the late 1950s and in the US since 1995, with large long-term trials and data from tens of millions of patients. It is on the WHO list of essential medicines.
Is metformin safe?
Yes for most people with type 2 diabetes, and that is why it has been the first medicine prescribed for decades. It lowers blood sugar without causing weight gain, and on its own it seldom causes hypoglycaemia. The common problem is the gut: in the US label's trial, 53% of people on metformin had diarrhoea against 12% on placebo, and 6% stopped because of it.
The Boxed warningThe strongest safety warning the US FDA puts on a medicine's label, printed inside a black border at the top.More in the glossary is for lactic acidosis, a dangerous build-up of acid in the blood. It sounds alarming, and it can be fatal, but it is rare. We score metformin 80, with strong marks for side effects, dependence and track record and a lower mark for the boxed warning.
How rare is lactic acidosis?
A Cochrane review of 347 trials and cohort studies found no cases in more than 70,000 patient-years of metformin use. Wider studies put the rate at about 3 to 10 per 100,000 patient-years, which is about the same as in people with diabetes who do not take metformin. In 2016 the FDA changed its kidney rules from a creatinine cut-off to eGFR, which let many people with moderate kidney disease keep taking it.
The cases that do occur almost always involve another problem that stops the body clearing metformin or lactate. The label lists:
- kidney function falling below an eGFR of 30, or sudden kidney injury from dehydration, vomiting or diarrhoea
- serious illness with low oxygen or shock, such as sepsis or heart failure
- heavy drinking or liver disease
- surgery and some scans with iodinated contrast dye
- age 65 or over
Early symptoms are vague: unusual tiredness, muscle pain, trouble breathing, sleepiness and stomach pain. Anyone with these symptoms on metformin, especially during an illness, needs prompt medical attention. Many doctors give "sick day rules" telling patients to pause metformin during vomiting or diarrhoea; ask your own team for theirs.
Vitamin B12
Long-term metformin lowers vitamin B12 absorption. In 29-week trials the label reports that about 7% of patients developed low B12 levels, and the risk grows with years of use. Low B12 can cause anaemia and numbness or tingling in the feet, which is easy to mistake for diabetic nerve damage. The label suggests a blood count every year and a B12 test every 2 to 3 years.
Doses and versions
| Version | Usual start | Maximum (US label) |
|---|---|---|
| Immediate release | 500 mg twice a day or 850 mg once a day, with meals | 2,550 mg a day |
| Extended release | 500 mg once a day with the evening meal | 2,000 mg a day |
| Children 10 and over | 500 mg twice a day | 2,000 mg a day |
Doctors increase the dose slowly, by 500 mg a week, to limit stomach upset. In 2020 the FDA asked several companies to recall some extended-release batches because of an impurity called NDMA, a probable carcinogen. Do not stop metformin over this; pharmacists can check whether your product is affected.
What it does not do
Metformin does not cause weight gain, and people often lose a little. It is not linked to liver damage in people without liver disease, and it does not need regular blood sugar checks to avoid hypos when taken alone. In the UK it is also used in pregnancy for some women with diabetes, under specialist care.
Overdose
Accidental extra doses rarely cause harm, but deliberate overdoses of tens of grams can cause severe lactic acidosis. The label says lactic acidosis was reported in about 32% of overdose cases. Hospitals treat it with dialysis. Call Poison Control (1-800-222-1222) or NHS 111 if someone has taken too much.
Who should be careful
Talk to your doctor or pharmacist if you have kidney or liver disease, heart failure or drink heavily, before any surgery or contrast scan, and if you take topiramate, dolutegravir or other new medicines. If you also take insulin or a sulfonylurea, learn the signs of low blood sugar.
How we scored it
Dependence (98), track record (95) and serious side effects (82) are strong. Regulatory warnings (50) reflect the lactic acidosis Boxed warningThe strongest safety warning the US FDA puts on a medicine's label, printed inside a black border at the top.More in the glossary and the 2020 NDMA recalls, and Overdose marginHow far a normal dose is from a harmful one. A wide margin means an accidental extra dose is unlikely to cause serious harm.More in the glossary (70) reflects the risk in large overdoses. Compare semaglutide, a newer diabetes drug, and atorvastatin, which many people with diabetes take too.
Questions people ask
Does metformin damage the kidneys?
No. Metformin is cleared by the kidneys but does not harm them. The concern runs the other way, since poor kidney function lets metformin build up. That is why the label asks for a kidney blood test (eGFR) before starting and at least once a year, and why it is not used when eGFR falls below 30.
How can I reduce stomach side effects?
Take it with meals, as the label directs. Doctors usually start low and increase slowly, and an extended-release version is often easier on the stomach. If diarrhoea or nausea persists, talk to your doctor or pharmacist rather than stopping on your own.
Can I drink alcohol while taking metformin?
The label warns against heavy drinking because alcohol increases the effect of metformin on lactate and can also cause low blood sugar. Light, occasional drinking with food is a common allowance, but ask your doctor what is safe for you.
Do I need to stop metformin before a scan?
Sometimes. For scans with iodinated contrast dye, the label says to pause metformin in people with moderate kidney impairment, liver disease, heart failure or heavy drinking, and to recheck kidney function 48 hours later. The hospital team will tell you if this applies.
Does metformin cause low blood sugar?
On its own it rarely does. The risk rises when it is combined with insulin or a sulfonylurea such as gliclazide or glipizide, or with heavy drinking and missed meals.
Sources
- 1.Metformin hydrochloride tablets label (opens in a new tab) · DailyMed, 2024
- 2.Metformin monotherapy for adults with type 2 diabetes and risk of lactic acidosis (Cochrane review) (opens in a new tab) · Cochrane, 2010
- 3.Metformin (opens in a new tab) · NHS, 2025
- 4.Metformin drug information (opens in a new tab) · MedlinePlus, 2025