Right and wrong about metformin

Not long ago, the Endocrine Credit Association of the Chinese Medical Association organized a number of clinical experts and pharmaceutical experts to formulate and publish the “Consensus of Experts on Clinical Application of Metformin” to guide Chinese clinicians and patients to correctly understand and rationally use metformin.

It is not common for an authoritative academic group, a group of top medical experts, to issue < < consensus > > for a single drug. Today’s free time, let’s also talk about metformin.

Before the text, let’s dispel the doubts that some people, especially conspiracy theorists, may have: [Is there any what issue in recommending a medicine with such great fanfare? ]

In fact, metformin is an old drug that has been in existence for more than 50 years. The [patent protection period] has long passed. Its production and sales are not monopolized by any pharmaceutical company. There are at least dozens of domestic manufacturers. Moreover, it is really cheap. The retail price of a bottle of domestic metformin tablets is less than 10 yuan, and the daily average drug cost spread to patients is only a few cents.

This is like hearing someone say: [An apple a day, keeps the doctor away] (an apple a day keeps the doctor away from me) and insisting that people are advertising Red Fuji. That is really a crime.

Cut the gossip and the text begins.

I. History of Metformin

Influenced by the long history and traditional culture of the Chinese nation, Many Chinese people prefer [natural Chinese herbal medicines] that have no toxic or side effects. However, the so-called [western medicine] through [chemical synthesis] is especially rejected. Metformin has also encountered similar situations in China, so I often explain to patients in clinical work as follows: [although metformin is a chemical drug, its discovery also comes from natural plants, and through scientific processing, the curative effect has been improved and toxicity has been removed.]

This is not nonsense, As early as the Middle Ages, There is a [folk prescription] circulating in the European continent: A kind of herbage called “Goat Bean” can improve the polyuria symptoms of diabetic patients. However, it was not until the beginning of last century that people knew that the plant was rich in [guanidine] compounds with scientific progress and development. Animal experiments proved that [guanidine] has the effect of lowering blood sugar, but it is also very toxic.

In order to fight against the incurable disease-[diabetes], which had no cure at that time, scientists devoted great enthusiasm to the transformation of [guanidine] and synthesized a series of guanidine derivatives. It was against this background that [metformin] appeared on the historical stage in 1929.

Anyone who knows the history of medicine knows that, A few years ago, in 1922, A great event of epoch-making significance took place: Insulin was discovered and applied clinically, and saved a large number of diabetic patients with miraculous curative effect. At that time, almost all doctors were immersed in the joy and enthusiasm of insulin, and they even believed with full confidence that diabetes would be completely solved from now on, [everything in the world is done.]

In the face of this dazzling and only king: insulin, metformin, which was not born at the right time, had to stop and wait silently in the dim corner for more than 30 years.

During these decades, The shortcomings of insulin are gradually exposed to the world. First of all, Inconvenient to use, Insulin is decomposed when it enters the stomach, Can’t take orally, The drug can only be administered by subcutaneous acupuncture of a syringe, Moreover, due to the short action time, It didn’t take long for the injection to be repeated. Under the condition that the concept of asepsis was not yet widely popularized at that time, Many diabetic patients even died of serious infection caused by injection. Although these problems have been basically solved with the progress of concepts and technologies such as standardized injection, ultra-fine needles, and the enrichment and perfection of medium and long-acting insulin preparations, the problems of inducing hypoglycemia and gaining weight still exist.

People urgently need more and better antidiabetic drugs, so it has set off an upsurge of drug development. In such an atmosphere, the biguanidine family naturally came to the front from behind the scenes. In the middle of the last century, phenformin, butylbiguanidine, metformin and other countries successively listed in the United States, Germany, France and other countries, and also had a moment of scenery.

However, just as the biguanide family emerged, tragedy also occurred at the same time. Doctors have gradually discovered in clinical application that phenformin may induce a complication with extremely high mortality rate: [lactic acidosis].

For any drug, Effectiveness is always inferior to security. Soon, Phenformin was completely kicked out of the market. Fortunately, although metformin and phenformin are under the same roof, their chemical structures are slightly different and have not caused such serious consequences. However, it can be imagined that [the fire in the city gate affected the fish in the pond], [originally from the same root] metformin is hard not to be deeply affected, and even struggling to withdraw from the market.

Second, gold always shines

With the advent of the era of evidence-based medicine, Beginning with the UKPDS (UK Prospective Diabetes Study), One after another, large-scale clinical trial studies have proved that metformin has excellent sugar control effect and good drug safety through hard facts, and even is considered to be the only hypoglycemic drug with definite cardiovascular benefits. Metformin’s prestige in diabetes treatment is also increasing day by day, becoming the core drug for global diabetes control.

In recent years, Major diabetes professional academic groups have issued guidelines to point out: For type 2 diabetes, unless there are special taboos, metformin should be used from the beginning, and metformin should also be included in the combined treatment plan. It can be seen that metformin is not even listed as a first-line choice with other drugs, but is regarded as the first choice beyond all similar drugs.

From the original bad time, bad start, to now yellow robe plus body, counter attack success. Metformin is proudly standing in the field of diabetes treatment as a king. Moreover, this crown was not crowned by any doctor, but a summary of the global diabetes treatment experience in recent decades.

Three, common misunderstanding

Regarding metformin, there are many common viewpoints or errors, which are clarified and explained below respectively.

1. [Metformin is only suitable for overweight or obese diabetics]?

Error. Major guidelines at home and abroad suggest that metformin has a wide range of applications, regardless of whether the patient is overweight or not.

2. [Metformin Can Lose Weight]?

Error. Metformin does show some weight loss effect for obese diabetics, but it is not a weight loss drug, and there is no definite weight loss effect for simple obesity.

3. [Metformin can prevent diabetes]?

Right. For people with pre-diabetes, metformin is the first drug that has been proved to prevent or delay diabetes. Some studies have confirmed that the incidence of diabetes decreased by 18% within 10 years with metformin intervention, but the incidence of diabetes decreased by 34% in another lifestyle intervention group. What if the two were combined? Think about it, you know!

4. [Metformin is only applicable to type 2 diabetes]?

Error. For type 1 diabetes, metformin combined with metformin can reduce the amount of insulin used by 10%, thus reducing the excessive weight gain caused by insulin use.

5. [The main mechanism of action of metformin is to inhibit liver gluconeogenesis]?

Right. Of course, metformin’s hypoglycemic mechanism goes far beyond that. In fact, to put it bluntly, doctors do not fully understand the exact mechanism of metformin’s action. In May 2014, < > magazine just published an article exploring its mechanism and found the inhibitory target of liver mitochondrial glycerol phosphate dehydrogenase. There are still too many gaps to be explored.

6. [Metformin often causes gastrointestinal reactions]?

Right. Gastrointestinal reactions are the most common adverse reactions of metformin, Including diarrhea, nausea, vomiting, gastric distension, dyspepsia, abdominal discomfort, etc., most of which occur in the first 10 weeks of medication. With the extension of treatment time, most patients will gradually tolerate or the symptoms will disappear. [small dose starts and gradually increases], which is an effective method to reduce adverse reactions at the initial stage of treatment.

7. [Metformin has hepatotoxicity]?

Error. Metformin is not metabolized by the liver, It does not compete for liver P450 enzyme, There is no hepatotoxicity. Only because there is less data on metformin use in patients with liver insufficiency, It is generally recommended to avoid using serum transaminase when it exceeds the normal upper limit of 3 times, and patients with mild high transaminase should closely monitor liver function when using it. Again, the reason for this is only to worry that the disease of the liver itself will affect the normal lactic acid clearance ability, not because metformin has what [hepatotoxicity].

8. [Metformin is nephrotoxic]?

Error. Metformin is mainly excreted through renal tubules in its original shape. The clearance rate is 3.5 times that of creatinine. It has no effect on renal function. Clinically, some doctors stop using metformin as soon as they see [proteinuria]. It is suggested to adjust the dose by estimating glomerular filtration rate (eGFR): no reduction is required when eGFR ≥ 60, reduction is required between 45 and 60, and withdrawal is required when eGFR is less than 45.

9. [Metformin is easy to cause lactic acidosis]?

Wrong. Although metformin’s eldest brother phenformin withdrew from the market for this reason, However, the barbaric era of [one person is guilty and every door is beheaded] is long gone. At present, there is no definite evidence that metformin is related to lactic acidosis. Metformin is not recommended at this time only in patients with renal impairment (eGFR < 45) and hypoxemia, because these two diseases are prone to lactic acid accumulation.

10. [Metformin Affects Vitamin B12 Absorption]?

Correct. Long-term administration of metformin can cause a decrease in vitamin B12 level. It is recommended to supplement vitamin B12 appropriately for this group of people.

11. [Metformin should be taken in dosage]?

Correct. At present, the dosage of metformin is low for most patients. Generally speaking, the minimum recommended dose is 500 mg/day, the maximum recommended dose is 2550 mg/day, and the optimal effective dose is 2000 mg/day. The dosage adjustment principle is [small dose starts, gradually increases].

12. [Metformin cannot be used in children with diabetes]?

Partly correct. Metformin is not recommended for children under 10 years old at present. Why? Never used, don’t know; For children over 10 years old, it can be used, has evidence and is very safe.

13. [Metformin cannot be used in elderly diabetic patients]?

Error. Metformin is still the first choice for elderly diabetics. There is no specific age limit. Its lower risk of hypoglycemia has unique benefits for the elderly. However, for patients over 80 years old, regular monitoring of renal function is recommended.

14. [Metformin cannot be used in patients with gestational diabetes mellitus (GDM)]?

Error. Metformin is a class B drug in the pregnancy drug classification, There was no increased risk of fetal malformation and neonatal complications, It has advantages in controlling pregnant women’s weight and improving insulin resistance. Metformin can also be used to prevent diabetes in the early stage of GDM. Although these views have long been a global consensus, However, China’s drug administration has not yet approved the application of metformin to pregnant women. When a scholar meets a soldier, the fist-sized man has the final say. Well, he has to change the answer to: correct against his will.

15. [Metformin has many other functions besides controlling blood sugar]?

Correct. The proven and definite additional benefits of metformin include cardiovascular protection, improvement of blood lipid, improvement of fatty liver (non-alcoholic), tumor inhibition, and treatment of polycystic ovary syndrome. Again, there is no weight loss effect.

16. [Metformin is the best drug for diabetes]?

Wrong. Although metformin was praised in the sky with a full article, However, it is still necessary to stay awake at the critical moment. For any disease, we should not only follow the guidelines, but also conform to the principle of individuation. For individual patients, there is never the best medicine [one size fits all], only the medicine that suits them better. Under good reasons and grounds, it is also correct and reasonable to use any other medicine.

I am convinced that one day metformin will also be removed from the throne by an existing or newly developed drug. At that time, we should not be surprised, because this is how medicine continues to develop.

Author: Zhang Zheng

The article was reprinted by Clove Garden authorized by the author.