Who Should Not Take Metformin

Metformin is prescribed to millions of people, and most of them tolerate it well. But its safety rests on one principle: not to prescribe it, and to temporarily discontinue it, where the risk of lactic acidosis rises. Our editorial team systematized the absolute contraindications, situations of temporary discontinuation, and special patient groups.

The logic of the contraindications: why it all comes down to lactate

Metformin suppresses gluconeogenesis in the liver, that is, it reduces the use of lactate to form glucose. Under healthy conditions this creates no problems: lactate is utilized, and excess drug is eliminated by the kidneys. Danger appears when several links of this system are disrupted at the same time.

The first link is the kidneys: if they work poorly, metformin accumulates. The second is the liver: with severe damage to it, lactate utilization declines. The third is the supply of oxygen to the tissues: in shock, severe cardiac or respiratory failure, cells switch to anaerobic metabolism and produce more lactate.

When these factors combine, metformin-associated lactic acidosis develops — a rare but potentially fatal complication. The review by DeFronzo and colleagues (2016) emphasizes that most such cases arise not because of the drug itself, but because of taking it against the background of an acute condition or severe organ failure.

This is precisely why almost all contraindications to metformin reflect one of these three links. When they are observed, the risk of lactic acidosis, according to the Cochrane review by Salpeter and colleagues (2010), does not exceed the background level in people with diabetes.

Absolute contraindications

Absolute contraindications mean that the drug is not prescribed. According to the instructions of the FDA and EU countries, they include the conditions listed below.

Until 2016, contraindications were defined by creatinine level, which often deprived people with moderate but stable kidney disease of the drug. The systematic review by Inzucchi and colleagues (2014) and subsequent decisions by the FDA and EMA switched the criteria to eGFR and permitted use down to a level of 30 ml/min/1.73 m² with a dose reduction.

For people with heart failure the approach also changed: stable chronic heart failure is no longer considered an absolute contraindication, and the prohibition concerns decompensated, acute conditions with hypoxia.

Alcohol deserves separate attention. Ethanol suppresses gluconeogenesis and lactate utilization, so regular alcohol abuse or episodes of heavy intoxication against the background of metformin increase the risk of both lactic acidosis and hypoglycemia.

When metformin is discontinued temporarily

Some situations are not a permanent contraindication but require temporarily stopping intake. The decision on this is made by a doctor, and resumption of intake occurs after the condition has stabilized.

• Studies with iodine-containing contrast:in patients with an eGFR of 30–60, liver diseases, alcoholism, heart failure, or with intra-arterial administration of contrast; kidney function is checked after 48 hours.
• Surgical interventions:especially under general anesthesia and with restriction of food and fluid intake.
• Acute conditions with dehydration:vomiting, diarrhea, high fever, severe infections, sepsis.
• Acute deterioration of kidney functionfrom any cause.

In many countries so-called “sick day rules” are practiced: during an acute illness with a risk of dehydration, a person temporarily stops taking metformin and some other medications (for example, diuretics, ACE inhibitors, SGLT2 inhibitors) until recovery. The specific list should be agreed on with a doctor in advance.

After discharge from the hospital or recovery, intake is resumed, but only provided that the person eats and drinks normally and kidney function has returned to a stable level.

A mistake that patients often make is to continue taking the usual dose during a severe intestinal infection, when they are barely drinking. It is precisely such scenarios that are described in clinical reports of lactic acidosis.

Special groups: pregnancy, children, the elderly

Metformin crosses the placenta. In the MiG study (Rowan et al., 2008), metformin in gestational diabetes provided control comparable to insulin and did not increase the frequency of complications in the short term, although some women required additional insulin. However, data on long-term outcomes for children are limited, so the ADA Standards consider insulin the preferred drug for diabetes during pregnancy.

In some countries metformin is used for polycystic ovary syndrome, including during pregnancy planning. The further decision on continuing intake after pregnancy occurs is made by a doctor individually.

In pediatrics, metformin is approved for treating type 2 diabetes in children aged 10 and older. Its use in children without diabetes, for example for “weight loss,” is not an indication and requires specialized evaluation.

In the elderly, the age-related decline in kidney function and more frequent acute illnesses increase the risks. Metformin is not contraindicated for them, but it requires regular monitoring of eGFR, careful attention to episodes of dehydration and, if necessary, a dose reduction.

Intolerance and conditions requiring caution

The most common reason people stop taking it is not a contraindication but gastrointestinal intolerance: nausea, diarrhea, bloating, a metallic taste. Usually these phenomena weaken over time, and a gradual increase in dose and extended-release forms improve tolerability.

Vitamin B12 deficiency is not a contraindication but requires correction. Particular care should be taken with patients who already have anemia or neuropathy, in whom long-term metformin use can worsen these conditions.

People who significantly restrict the calorie content of their diet, fast, or perform prolonged, exhausting exercise without fluid replacement have a higher risk of dehydration. For them, the question of taking metformin should be discussed with a doctor separately.

Finally, metformin is not a means of weight loss in people without metabolic disorders. Taking it without indications combines real, if rare, risks with dubious benefit.

Editorial conclusions

Metformin is contraindicated with an eGFR below 30, metabolic acidosis, states of tissue hypoxia, hepatic failure, and alcohol abuse — that is, where the risk of lactic acidosis rises.

Temporary discontinuation is needed for studies with contrast in risk groups, operations, and acute conditions with dehydration.

Pregnancy, childhood, and old age are situations where decisions are made individually, taking into account alternatives and regular monitoring of kidney function.

To learn more, read our materials on the effect of metformin on the liver and kidneys, on tests during its use, and on the drug’s side effects.

References

1. U.S. Food and Drug Administration. FDA Drug Safety Communication: FDA revises warnings regarding use of the diabetes medicine metformin in certain patients with reduced kidney function. Silver Spring: FDA; 2016.
2. Inzucchi SE, Lipska KJ, Mayo H, Bailey CJ, McGuire DK. Metformin in patients with type 2 diabetes and kidney disease: a systematic review. JAMA. 2014;312(24):2668–2675.
3. Salpeter SR, Greyber E, Pasternak GA, Salpeter EE. Risk of fatal and nonfatal lactic acidosis with metformin use in type 2 diabetes mellitus. Cochrane Database Syst Rev. 2010;(4):CD002967.
4. DeFronzo R, Fleming GA, Chen K, Bicsak TA. Metformin-associated lactic acidosis: current perspectives on causes and risk. Metabolism. 2016;65(2):20–29.
5. Rowan JA, Hague WM, Gao W, et al. Metformin versus insulin for the treatment of gestational diabetes. N Engl J Med. 2008;358(19):2003–2015.
6. American Diabetes Association Professional Practice Committee. Standards of Care in Diabetes—2025. Diabetes Care. 2025;48(Suppl 1).
7. European Medicines Agency. Use of metformin to treat diabetes now expanded to patients with moderately reduced kidney function. London: EMA; 2016.