This issue has to be discussed in context.

The first thing I have to tell you is that, well, metformin does have the potential to hurt your liver. As a drug, metformin can't escape the established trope of drugs - it may have an effect on liver and kidney function. For this reason, metformin is not recommended for patients with liver insufficiency or cirrhotic decompensation. Not because metformin actually hurts the liver. In fact, because metformin is not metabolized by the liver, it is not actually hepatotoxic. The reason why metformin is not recommended for people with serious liver problems is that there are currently fewer applications of metformin in this group of people, and there is no way to validate its safety. To be on the safe side, it is not too late to wait until liver function has recovered before taking it.

For others, there is absolutely no need to worry about metformin hurting the liver. In fact, because it improves the degree of fatty liver, controls weight, and reduces LDL in the blood, metformin also protects the liver in some ways.

For type 2 diabetics, metformin has been tested for 60 years for its safety as a first-line drug for lowering sugar. There are bigger demons and ghosts that have been tried and tested for 60 years. Metformin is a pretty safe old drug. As a first-line drug, clinicians are more than happy to recommend that all patients with type 2 diabetes should take metformin as long as there are no contraindications and they can tolerate the side effects of the drug. Not to mention that it has additional benefits such as cardiovascular risk reduction, anti-aging, and anti-tumor. Personally, I would recommend taking metformin for long-term glucose reduction as long as you don't have severe liver insufficiency, which is perfectly fine.

Author

Chen Dashu, female, graduated from Southeast University School of Medicine with a master's degree, specializes in the diagnosis and treatment of all kinds of common diseases and critical illnesses in Obstetrics and Gynecology, especially in the direction of prenatal diagnosis and gynecological endocrinology, and has long been solving all kinds of problems for patients.

Metformin is a kind of biguanide oral hypoglycemic drugs, because of its low price and significant effect, applicable to a wide range of diabetic population, therefore, it is currently the most common clinical use of oral hypoglycemic drugs, mainly for simple dietary control of diabetic patients are not satisfied with the efficacy of the efficacy of diabetes mellitus, especially for obesity and accompanied with hyperinsulinemia efficacy, and therefore by many diabetic patients, the favor! However, it will inevitably produce certain side effects, although its side effects and other types of drugs compared to less, but also can cause mild gastrointestinal reactions and the occurrence of skin rashes, if the patient's renal function is reduced, the metabolites can be a large number of accumulation in the body, causing hyperlacticemia or lactic acidosis, therefore, when taking the drug should be regularly monitored renal function, on liver function. There is no definite report on whether there is any damage to the liver function, however, for safety reasons, it is better to monitor the liver function when monitoring the renal function, and adjust the medication according to the condition of liver and kidney function.

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Dr. Duan Q&A Online 🍀Chat About Metformin 🍀

In Dr. Duan's mind there are two "magic drugs", respectively, aspirin and metformin, today we will talk about metformin in detail.

Let's start with a couple of clear answers:

Answer 1: Metformin is not only non-hepatotoxic but also non-nephrotoxic. If liver function is normal, receiving the recommended dose of metformin will not cause liver damage;

Rationale: Metformin is metabolized in the body mainly by the kidneys and is cleared rapidly. Meanwhile, studies have shown that metformin not only does not damage the kidneys, but may also have a protective effect;

Metformin is absorbed into the circulation through the gastrointestinal tract, hardly binds to plasma proteins, does not undergo hepatic metabolism, does not compete for hepatic P450 enzymes, and is not degraded in vivo; instead, it acts directly on the liver and muscles to reduce gluconeogenesis and increase glucose catabolism.

Therefore, metformin has no liver or kidney damage.

Answer 2: Those with impaired liver function should be cautious about taking metformin because impaired liver function can significantly limit lactate metabolism.

RATIONALE: Although there is no clear evidence that metformin is associated with lactic acidosis and lactic acidosis does not occur with long-term use when the liver and kidneys are normal. However, when there is hepatic or renal impairment it may lead to accumulation of metformin and lactic acid, which can increase the risk of lactic acidosis.

Then why does Metformin belong to the "miracle drug" in Dr. Duan's mind?

(1) Metformin is the drug of choice and the whole course of treatment for type 2 diabetes mellitus, which is safe and inexpensive;

② Metformin is the only oral hypoglycemic agent that can reduce body weight and can effectively improve body mass index;

③ Metformin can improve insulin resistance and can prevent or delay the onset of diabetes, but there is no indication for metformin to prevent diabetes in China;

④ Metformin is effective in cardiovascular protection and reduces the risk of cardiovascular death;

⑤ Metformin improves fat synthesis and metabolism and effectively improves total cholesterol;

(vi) Metformin showed significant improvement in hepatic inflammation, steatosis and fibrosis;

(7) Metformin is effective in improving diastolic blood pressure;

(8) Several meta-suggestions suggest that metformin treatment is associated with a reduced risk of lung, prostate, and rectal cancers.

Dr. Duan's special reminder

1. The so-called "miracle drug" is not a cure for all diseases, but rather a wide range of effects, side effects are relatively small, inexpensive, and patients benefit from treatment;

2. The most common side effect of metformin is gastrointestinal reaction, which mostly occurs in the first 10 weeks of use and is mostly tolerated;

3. Any good medicine should be given under the guidance of a professional physician or pharmacist for the right condition and not abused;

4. Before contrast or general anesthesia, the timing of discontinuation of metformin is selected based on renal function;

5. Friends suffering from diabetes, timely in the case of medication still can not forget to control diet and moderate exercise!

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Metformin is the drug of choice and the cornerstone drug for patients with type 2 diabetes, and several guidelines for diabetes state that if there are no contraindications, metformin should be the drug of choice for glycemic control in patients with type 2 diabetes and has been retained in the therapeutic combination of diabetic medication regimens. Long-term consumption of metformin, many friends worry that it will hurt the liver, really? In fact, metformin, the drug itself, has no adverse effects on liver health, but for those with liver function problems, taking metformin should be based on the situation.

Although metformin has been used clinically for decades and is an old drug, at the same time it is a good drug, a classic drug, and its clinical status in diabetes treatment is currently irreplaceable. In addition to type 2 diabetes, metformin can be used for type 1 diabetes, polycystic ovary syndrome patients with abnormal regulation of glucose metabolism, the prevention of diabetes risk and many other aspects, in addition to being able to help the control of blood glucose, long-term use of metformin, there is a cardiovascular system benefit, reduce the risk of cardiovascular disease, that is to say, long-term use of metformin, not only can lower blood sugar, there is a certain That is to say, long-term use of metformin can not only lower blood sugar, but also has a certain cardiovascular protective effect.

After metformin is taken orally into the body, it is absorbed into the body in the gastrointestinal tract, and peaks in blood concentration at about 5.1 hours.It is finally excreted from the body via the kidneys in its prototype form, with approximately 90% of the drug passing through the kidneys after 24 hours of oral administration.This drug is not bound to plasma proteins and is not metabolized by the liver, so while one of the mechanisms of metformin's hypoglycemic action is through inhibition of hepatic glycogen output, this taking of metformin itself, has no adverse effects on the liver.

In addition to having no effect, it has also been found that metformin has shown significant improvement in serologic enzyme profiles and metabolic abnormalities of the liver in patients with NAFLD, but histologic changes were not significant. Therefore, it can be said that metformin not only does not harm the liver, to some extent, there is a certain protective effect on the liver. In addition to liver protection, long-term use of metformin, for lipid metabolism, blood uric acid metabolism have a certain positive regulatory effect, for diabetes combined with high blood fat, high uric acid and other problems, metformin are good drugs can be taken.

Long-term use of metformin during the liver function abnormalities, on the one hand, consider taking other drugs, on the other hand, consider their own physical reasons for the impact, rather than attributable to long-term use of metformin. For example, if you take metformin interval, also take statin drugs to control blood lipids, then the problem of elevated transaminases, it is likely to be the effect of statin; if you are taking metformin during the period, you have not given up the habit of long-term large amount of alcohol, then if your liver problems, it is more likely to be the role of alcohol, and not necessarily the role of drugs.

If liver function problems, then taking metformin should be careful, this attention is not because metformin itself has liver toxicity, but because the weakening of liver function will affect the body's ability to clear lactic acid, increasing the risk of metformin-induced lactic acidosis, therefore, for severe liver function impairment, transaminase elevation of more than three times, generally need to stop using metformin, and mildly patients with elevated transaminases should also pay more attention to regular monitoring of liver function.

Metformin is a good drug, but it is not without its drawbacks. Metformin's biggest adverse reaction is to cause gastrointestinal discomfort, nausea, vomiting, abdominal pain, diarrhea, constipation and other gastrointestinal adverse reactions are easy to take metformin adverse reactions, therefore, we generally recommend that the application of this drug at the beginning of the initial period, to be a low dose of the start of the medication, if the medication during the period of time, the body to tolerate the good, and then gradually increase the dose, which will greatly improve the tolerance and compliance with the medication. This can greatly improve the drug tolerance and drug compliance. In addition, the long-term use of this drug will affect the absorption of vitamin B12 in the body, during the use of the drug, you should also pay more attention to vitamin B12 supplementation.

Metformin occupies an irreplaceable position in the treatment of diabetes. It can not only reduce fasting blood glucose, but also reduce postprandial blood glucose; while lowering blood glucose, it can also improve insulin resistance and increase the glucose-lowering effect of sulfonylurea glucose-lowering drugs and insulin; with long-term application, it can significantly reduce glycated hemoglobin by about 1-2%. Therefore, Metformin has become a must-use drug for almost every diabetic patient.

Metformin adverse reactions are mainly gastrointestinal adverse reactions, such as nausea, vomiting, diarrhea, abdominal pain, etc. Taking with food or switching to metformin enteric-coated tablets can reduce the adverse reactions. Taken with food, metformin absorption rate and degree of absorption will be slightly affected, but the efficacy of the sugar will generally have little effect, after all, to reduce gastrointestinal reactions, can increase the patient's adherence to treatment. After all, reducing the gastrointestinal reaction can increase the patient's adherence to the treatment. Even if the efficacy is affected, we can still increase the dosage of metformin to achieve the desired glycemic efficacy.

As for whether metformin can harm the liver, it hardly ever happens. Because metformin, after being absorbed, is not metabolized by the liver and is directly excreted from the kidneys as the prototype drug, it has little or no effect or injury on the liver. However, liver function damage has been reported during use, but after stopping the use of metformin, the liver function of these patients returned to normal.

It is important to note that metformin needs to be used with caution if there are inherent abnormalities in liver function or if there are liver-related diseases. This is because the most serious adverse reaction to metformin is lactic acidosis, which is extremely rare, but when it occurs, it is often life-threatening. In cases where lactic acidosis has occurred, there have been patients with concurrent comorbidities of liver disease, so metformin is not recommended for patients with liver disease as a precautionary measure.

In addition, some patients using metformin are very confused about when to take it, please remember: if it is a metformin tablet, take it with a meal; if it is a metformin extended-release tablet, take it with dinner; if it is an enteric-coated metformin tablet, please take it half an hour before a meal. The aim is to minimize gastrointestinal reactions.

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Metformin is primarily used to treat type 2 diabetes, which is primarily due to relative insulin underproduction and concomitant insulin resistance.

The pathogenesis of type 2 diabetes mellitus begins with insulin resistance, followed by an increase in compensatory insulin secretion and a gradual progression of insulin deficiency after an increased pancreatic load, leading to diabetes.

The role of metformin

1. Hypoglycemic effect

Inhibits gluconeogenesis, reduces hepatic glycogen output, and delays intestinal glucose absorption; increases glucose utilization by peripheral tissues.

2, weight loss effect

Metformin has a weight-reducing effect, which is effective in overweight and obese patients and has no weight-reducing effect in normal-weight patients. So the drug isDrugs of choice for obese type 2 diabetes mellitus。

3、Lowering fat and cholesterol

Metformin not only has a good hypoglycemic effect, but also lowers total cholesterol and triacylglycerol levels by inhibiting cholesterol synthesis and storage.

4, Metformin anti-inflammatory, improve insulin resistance

Metformin inhibits the release of many inflammatory factors and has a significant anti-inflammatory effect. Inflammation is associated with tissue insulin sensitivity and glucose metabolism, so anti-inflammatory treatment improves insulin sensitivity and glucose metabolism in diabetic patients. Thus treating diabetes.

Side effects of metformin

Despite all the advantages of metformin, any drug has a therapeutic effect, and any effect not related to treatment is a side effect. Metformin inhibits the absorption of intestinal sugar when taken orally, and there are definitelygastrointestinal refluxshould, in addition, be absorbed through the gastrointestinal tract and then enter the liver for biometabolism, if theMay cause liver damage with long-term applicationHowever, liver damage from metformin has been clinically reported, but overall liver damage from metformin is rare, and the vast majority of metformin is excreted through the kidneys in the form of urine.

Thus, there are recommendations in the pharmacopoeia thatThe drug is used with caution in patients with abnormal liver and renal function, and long-term application requires monitoring of liver and renal function.

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In addition to its reliable hypoglycemic effect and lowering of glycosylated hemoglobin, metformin has a cardioprotective effect that reduces the risk of cardiovascular disease complicating diabetes.

It is the most widely used of the oral hypoglycemic agents, and the drug is the first-line medication recommended by current guidelines. The guidelines state that metformin should be used as the first choice and basic medication whenever there are no contraindications.

The instructions for metformin remind patients that the use of metformin certain people may lactic acidosis will be combined with liver impairment, patients with liver disease need to be careful with the use of metformin, some people mistakenly believe that metformin has hepatotoxicity.

In fact, metformin is not metabolized by the liver and does not compete for the liver p450 enzyme, which in itself is not damaging to the liver. But some people need to be careful with metformin if they have liver insufficiency.

This is because the use of metformin causes the body to produce more lactic acid, and if the liver is not functioning well, the ability to remove lactic acid is reduced, and lactic acidosis may result. This is the reason why metformin is used with caution for liver insufficiency, not because metformin is damaging to the liver.

In patients with hepatic insufficiency, if metformin is to be used, liver enzyme indices need to be monitored; if the transaminases are more than three times the upper limit of normal, it is not recommended, and if they are only mildly elevated, they can be used with caution and increased supervision.

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Metformin is the cornerstone of the treatment of type 2 diabetes mellitus, recommended as the first-line drug of choice for the treatment of type 2 diabetes mellitus by major domestic and international guidelines and textbooks, mainly through reducing hepatic glucose output, inhibiting gluconeogenesis, increasing glucose uptake and utilization by peripheral tissues, such as muscle and fat, promoting anaerobic fermentation of glucose, inhibiting glucose uptake in the small intestine and lowering blood glucose, the use of metformin alone can effectively reduce Fasting blood glucose, postprandial blood glucose and glycosylated hemoglobin, if metformin monotherapy blood glucose can not reach the standard, can be combined with any other kinds of oral hypoglycemic drugs, so that blood glucose control has been significantly improved, metformin and insulin combination, the blood glucose standardization rate is high, it can reduce the dosage of insulin, reduce the risk of hypoglycemia and weight gain. In addition, metformin has a clear cardiovascular protective effect, and long-term use can significantly reduce the risk of cardiovascular disease in patients with type 2 diabetes. In conclusion, metformin is safe and well tolerated, gastrointestinal adverse effects are often transient, there is no nephrotoxicity, hypoglycemia rarely occurs when used alone, and long-term use does not increase the risk of lactic acidosis. For type 2 diabetic patients without contraindications to its use, metformin should be used as a full course of medication and always retained in the treatment regimen.

Metformin is absorbed into the blood circulation through the small intestine after oral administration, hardly binds to plasma proteins and does not undergo hepatic metabolism, has no effect on hepatic drug enzymes, and is not converted in the body; instead, it acts directly on the muscle and liver, inhibits glycogen isomerization, and increases the uptake and utilization of glucose by the muscle; therefore, metformin is not hepatotoxic, and patients with normal hepatic function, who receive conventional doses of metformin will not cause liver injury. Metformin is mainly excreted as a prototype in the urine via the kidneys, and renal tubular excretion is the main route of metformin clearance from the body. The clearance of metformin via the kidneys can reach 90% within 24 hours after oral administration, which can be considered as rapid clearance.

Metformin can promote lactic acid production and inhibit lactic acid metabolism during glucose lowering, so patients with renal insufficiency or overdose of metformin are prone to metformin accumulation in the body, which increases the risk of lactic acidosis.Although metformin is not hepatotoxic, patients with hepatic insufficiency should be cautious in using metformin, this is because the impaired hepatic function makes the ability to remove lactic acid in the body limited. To a certain extent, it increases the risk of lactic acidosis. Therefore, metformin should be avoided in patients whose serum aminotransferase is higher than three times the upper limit of normal value or who have severe hepatic insufficiency, while patients with mildly elevated serum aminotransferase should be closely monitored for their liver function. In addition, some studies have shown that metformin can significantly reduce serum aminotransferases, improve hepatic inflammation, fibrosis and steatosis, and can be used as an adjunct in the treatment of NAFLD, so metformin is not only non-hepatotoxic, but also has a protective effect on the liver. It is worth noting that if symptoms such as fatigue, loss of appetite, discomfort in the right upper abdomen, soy sauce-colored urine, itching, and jaundice occur during the administration of metformin, it indicates that the patient may be experiencing hepatic damage, and at this time liver function tests should be performed promptly to determine whether or not to discontinue the drug. There have been isolated reports of liver function abnormalities occurring with metformin, but they are often due to the combination of other medications that cause liver function impairment, and most of them return to normal when metformin is discontinued.

In conclusion, metformin is an important drug for the treatment of type 2 diabetes mellitus, which is not metabolized by the liver in vivo, and is mainly excreted as a prototype through the renal tubules without liver toxicity, and it is safe and effective in patients with normal hepatic function, taking it at the recommended dosage; patients with severe hepatic impairment are at risk of lactic acidosis, and should avoid using metformin.

References:

Metformin Tablets Instructions

Chinese Guidelines for the Treatment of Nonalcoholic Fatty Liver Disease (2010 Revision)

Expert Consensus on the Clinical Use of Metformin (2016 Edition)

Shao Laitang. A case of metformin hydrochloride causing abnormal elevation of ghrelin transaminase [J]. Jiangsu Pharmacology and Clinical Research, 2004, 12: 82.

Metformin, along with aspirin, is one of the two great miracle drugs in the field of Western medicine, and I'll have time to properly educate you on the amazing uses of both drugs.

To some extent biguanides are antihyperglycemic, not hypoglycemic. This is so because they promote normalization of hyperglycemia, but they do not or rarely cause hypoglycemia when applied alone. Biguanides can be used either as monotherapy or with other oral hypoglycemic agents. They can exacerbate hypoglycemia caused by other hypoglycemic drugs.

Metformin reduces insulin resistance, decreases hepatic glucose output, and enhances peripheral glucose uptake. Enhanced inhibition of gluconeogenesis via insulin reduces glucagon stimulated gluconeogenesis and increased glucose uptake by muscle and fat cells. These changes result in a 20% to 40% reduction in fasting and postprandial glucose, a reduction in hemoglobin A1C, a slight decrease in body weight, a decrease in low-density lipoprotein (LDL), and an increase in high-density lipoprotein (HDL) in diabetic patients.

Toxicity of Metformin

A serious toxicity of metformin is lactic acidosis (symptoms of lactic acidosis include anorexia, nausea, vomiting, abdominal pain, lethargy, hyperventilation, and hypotension), but it can lead to hypoglycemia in combination with other glucose-lowering agents.

对于肝功能正常的患者并没有发现其有引起肝损伤的报道，相反，在对非酒精性脂肪肝患者中，二甲双能改善其肝脏血清学酶谱及代谢异常，具有一定的保护肝脏作用。

However, the use of metformin in patients with the following risk factors increases the risk of lactic acidosis, so the advantages and disadvantages of using metformin should be weighed and the relevant indicators should be actively monitored in patients with the following risk factors, which are as follows:

● Impaired renal function (glomerular filtration rate [eGFR] <30 mL / min)

:: Complicated liver disease

:: Alcoholism

:: Instability or acute heart failure

● History of lactic acidosis during metformin therapy

● Lack of tissue perfusion or hemodynamic instability

:: Hypoxic state or severe acute illness.

In addition, attention should be paid to its risk of causing VB12 deficiency.

Metformin is one of the most commonly used oral hypoglycemic agents and is also used as the drug of choice for first-onset diabetes.In 2014, China developed the Expert Consensus on the Clinical Application of Metformin. In the consensus, it was re-emphasized that metformin is the first-line drug for diabetes and should always be retained in the diabetes treatment regimen if there are no contraindications. Because it can not only effectively reduce blood glucose, but also has many other benefits, for example: in the current use of hypoglycemic drugs, metformin is the only drug that has been proven to significantly reduce the risk of diabetes-related coronary heart disease, stroke and other cardiovascular complications; can reduce low-density lipoproteins, assist in the treatment of atherosclerosis; but also reduce the risk of cancer in patients with diabetes, and so on. There is also a very important point, metformin price is relatively cheap, long-term use, the people can afford. Such a good drug, many people due to the existence of such a misunderstanding: metformin hurt the liver and kidneys and afraid to use it, that the real situation in the end what is it like?

Whether a drug harms the liver and kidneys depends mainly on the pharmacokinetic characteristics of this drug. Metformin is absorbed through the gastrointestinal tract for blood circulation, without hepatic metabolism, and acts directly on the liver and muscle to reduce blood glucose by decreasing hepatic gluconeogenesis and increasing muscle glucose anaerobic fermentation. Therefore, metformin is not hepatotoxic. Metformin is excreted primarily in the urine in its native form and is cleared rapidly in the kidneys, with 90% being removed within 12 hours. Therefore, metformin is also not damaging to the kidneys.

However, the use of metformin is limited by liver and kidney function, and caution should be exercised in the use of metformin in diabetic patients who already have hepatic and renal impairment. Metformin should be avoided when liver function exceeds three times the upper limit of normal; and when blood creatinine in patients with renal impairment exceeds 1.5 mg/dl for men and 1.4 mg/dl for women.

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