After seeing that metformin’s drug instructions state that it is contraindicated in patients with renal insufficiency, many patients naturally have the concern that metformin will harm their kidneys. In fact, metformin has been used to deal with diabetes for more than 50 years, not only has it not been eliminated, but has received more and more attention, and in recent years it has been listed by authoritative organizations as the first-line drug and starting drug for the treatment of type 2 diabetes, which shows that the efficacy and safety of metformin have stood the test in long-term clinical application. Renal excretion ≠ kidney damage Although metformin is excreted from the kidneys, it is not toxic to the kidneys and does not damage the kidneys. A large number of clinical studies have confirmed that metformin is not harmful to liver and kidney function when taken by patients with normal liver and kidney function within the regular dosing range. Therefore, the view that metformin can harm the kidney is a misconception. The instructions state that metformin is prohibited in patients with renal insufficiency, not because metformin itself will damage the kidneys and further deteriorate renal function, the reason is that metformin will promote the anaerobic enzymolysis of glucose and increase the production of lactic acid, if the patient’s renal insufficiency, metformin can not be excreted normally, and accumulate in the body, when lactic acid is increasing in the blood, there is a possibility of lactic acidosis . It is for these reasons that metformin is prohibited in patients with renal insufficiency. French diabetologist Jean Sterne is considered to be the key figure in the discovery of the effects of metformin, he conducted the first human study of metformin, and gave it the name “Glucophage” (glucophage, Chinese trade name “Gevaizhi “In 1957, Sterne published a research paper on metformin, and almost simultaneously, papers on metformin’s siblings, phenelzine and butylguanidine, were also published. Metformin was marketed in France, phenylethylguanidine in the United States and the Nordic countries, and butylguanidine in Germany. In the initial competition, metformin was barely competitive with the powerful hypoglycemic phenelzine due to its weak hypoglycemic effect, and its application was almost limited to France. Phenethidine made a big splash in the 1960s, but “no man is good for a thousand days, no flower is good for a hundred days”, and American scientists gradually discovered its higher risk of causing lactic acidosis, a complication with a high mortality rate. at the end of the 1970s, phenethidine was almost completely withdrawn from the market, and metformin, which also belongs to the biguanide family, was also affected, and was once recommended to be withdrawn from the market, and thus again fell into a situation of being left out and misunderstood. After metformin was withdrawn from the market, Sterne and other researchers did not back off and still insisted on further exploration, and subsequent studies conducted one after another found that metformin has a completely different mechanism of action than sulfonylurea oral hypoglycemic agents – due to the different molecular structure, it does not inhibit the release and oxidation of lactic acid, resulting in lactic acidosis The incidence is also far lower than that of its two brothers, except that this concern was subjectively exaggerated at the time. The facts speak for themselves, and the study data show that the occurrence of lactic acidosis with metformin treatment is very rare. A meta-analysis showed that the incidence was less than 1 in 100,000 cases. Another study showed no evidence that metformin was associated with risk of lactic acidosis and increased lactate levels. As for the cases of lactic acidosis in case reports, they are due to incomplete mastery of the contraindications of metformin (e.g., liver and kidney insufficiency, heart failure, acute infection, etc.) by physicians or patients. It’s gold that always shines Because metformin has additional effects such as weight control, increased insulin sensitivity and cardiovascular protection, in addition to effective glucose lowering, it is recognized by the medical field and patients worldwide. In addition to treating diabetes, metformin is routinely used in clinical settings to treat polycystic ovary syndrome (a common condition that afflicts women of childbearing age, often accompanied by insulin resistance). In addition, metformin may reduce the risk of tumors in diabetic patients, and perhaps it could be used for cancer prevention and treatment in the future. Some studies have also found that metformin has the potential to improve the symptoms of NAFLD, prevent and treat uveitis, a common blinding disease, and reduce the prevalence of Parkinson’s disease, among other potential effects. Despite the ups and downs, metformin’s discovery journey reaffirms that gold always shines. It is deservedly the cornerstone of oral therapeutics for type 2 diabetes.