In recent years, the popularity of metformin has become higher and higher, and it has gradually become a star drug in the diabetic lowering world. It is widely recommended because of its strong efficacy, low cost, low risk of hypoglycemia, etc., and is a first-line drug for the treatment of type II diabetes.
Recently, metformin has been exposed to contain carcinogens, which has caused many controversies for a time. For patients, whether metformin can still be eaten is their biggest concern.
Since its introduction in the 1950s, metformin has become one of the most widely used classic oral hypoglycemic drugs in the world. Metformin is a hydrophilic small molecule drug that not only has the effect of improving blood glucose tolerance in patients with type 2 diabetes, but also lowering the basal and postprandial blood glucose. Moreover, the mechanism of action of metformin is somewhat different from other types of oral antiglycemic drugs.
Metformin can reduce the production of liver sugar, reduce the absorption of sugars, but also increase the intake of peripheral sugars and effective utilization, thereby improving insulin sensitivity; in addition, because metformin hypoglycemic efficacy is better, can protect cardiovascular, less adverse reactions, and the price is easy to make patients accept, is a well-deserved type 2 diabetes preferred drug.
Metformin is inexpensive and potent, and is a boon for people with type 2 diabetes. However, in June 2020, the US Food and Drug Administration (FDA) issued a document saying that in some metformin extended-release preparations, the content of n-nitrosamines (ndma) impurities exceeded the standard, and recommended that some companies voluntarily recall.
However, this is not the first time that ndma has been found in metformin, after, in July 2018, the European Medicines Agency issued an announcement that ndma was detected in zhejiang Huahai valsartan APIs, triggering a variety of valsartan drug recalls. In September 2019, the FDA announced that ranitidine drugs had detected low amounts of ndma. In April 2020, the FDA ordered all producers to immediately withdraw all ranitidine products from the U.S. market.
ndma is a common n-nitrosamine compound that is soluble in solvents such as water, ethanol, and dichloromethane, and is found in water, roast meat, bacon, vegetables, and dairy products.
Clinical trials have proved that this substance is highly toxic, can directly or indirectly damage cellular DNA, produce genetic mutations or mutagenic mutations in the body, have carcinogenic possibilities or tendencies, and are characterized by also interacting with DNA at low levels, resulting in DNA mutations or carcinogenicity. Therefore, the discovery of ndma in metformin has also made people doubt the safety of metformin.
However, before that, metformin has been shown to have anti-tumor effects.
A 2005 epidemiological study noted that there was a direct link between diabetics using metformin and reducing cancer risk. A South Korean study published in the well-known medical journal Journal of Thoracic Oncology analyzed data from more than 730,000 people and concluded that "taking aspirin, statins and metformin was significantly negatively correlated with lung cancer risk, while those taking the drug were at lower risk", which also shows that metformin is independently associated with a reduced risk of lung cancer and has a synergistic effect with other drugs.
The American Diabetes Society and the American Cancer Society jointly published the "Diabetes and Cancer Consensus Report" in 2010, which pointed out that diabetes mellitus (mainly type 2 diabetes) is associated with an increased risk of liver cancer, pancreatic cancer, endometrial cancer, colon/rectal cancer, breast cancer, and bladder cancer, so hypoglycemic reduction is very important to reduce the risk of cancer.
Since metformin has an anti-cancer effect, will the carcinogenic impurities found in its composition affect the efficacy of metformin?
In fact, the causes of ndma impurities in metformin are complex and diverse, which may come from raw materials, or from production, packaging and storage processes. However, there are more effective detection methods, such as gas chromatography-mass spectrometry (gc-ms) method, pre-column derivatization of high performance liquid chromatography (hplc) method to determine the ndma genotoxic impurities in metformin.
There are also prescribed inspection methods in pharmacopoeias such as the European Pharmacopoeia (9.0 Edition), which provide technical reference for effective control of drug quality. Therefore, the situation that metformin contains carcinogenic impurities is completely within the controllable range, which is not contradictory to the anti-cancer effect of metformin itself.
Metformin has a reliable hypoglycemic effect, is generally well tolerated, has both anticancer effects, and does not increase the risk of hypoglycemia. However, metformin also has certain side effects, the most common side effects are gastrointestinal reactions, such as diarrhea, loss of appetite, etc., which lead to malnutrition, but the symptoms are mild and transient and dose-related. In patients taking the drug, about 50% of patients develop this symptom.
Experts recommend that during the medication process, the dose should be started in small doses, gradually increased, and the dose should be adjusted in a timely manner, and the non-extended-release preparation should be taken with meals in parts, or changed to a sustained-release preparation once/ day, which can reduce gastrointestinal reactions.
In addition, patients with renal insufficiency, especially in the case of often deteriorating renal function, the continuous accumulation of toxic metabolites in the patient's body will cause the patient's anorexia and digestive dysfunction, coupled with the patient's strict restriction of protein intake, a variety of metabolic process disorders in the body, resulting in a high incidence of malnutrition.
Studies have shown that elderly patients with chronic renal insufficiency older than 60 years of age are more likely to develop malnutrition than elderly patients with non-chronic renal insufficiency. Therefore, when diabetic patients with renal insufficiency use metformin, it will bring further harm to the body and aggravate malnutrition. Therefore, the dose needs to be adjusted or discontinued according to the renal function.
Metformin is an oral hypoglycemic drug with significant characteristics of the current application rate, which has shown a significant application effect in single-use drugs and combination drugs, and has been widely used in the prevention of cardiovascular complications of diabetes and blood glucose control, which has become a key drug during the treatment of diabetic patients. However, there is still a need for attention to detail in the use of metformin to improve the safety of drug applications. #Breeze Project##Guardian of Health ##谣零零计划 #
Resources: [1] "Analysis of application methods for reducing metformin side effects". Electronic Journal of General Practice Stomatology.2019-06-15 [2] "Scientific Understanding and Facing the Nutritional Risks of Long-term Oral Drugs". Chinese Journal of Clinical Health Care.2019-12-27 [3] Research progress on metformin gastrointestinal intolerance. Modern Medicine and Clinical.2019-02-26
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