Metformin is the first line of treatment for type 2 diabetes. Low prices and few adverse reactions make it a large number of users worldwide. Due to the emergence of insulin, the biguanide has disappeared from people’s attention for decades. In fact, metformin is a biguanide derived from the pharmacologically active ingredients of plant goat beans. Goat Bean has many names. It was used in the Middle Ages to treat diseases such as snake bites, plagues, frequent urination, and parasites. In 1922, Werner and Bell made a biguanide from goat beans. In 1929, Slotta and Tscheche found that the drug could lower blood sugar. In the 1950s, France approved the use of metformin, buformin, and phenformin in the treatment of type 2 diabetes. In the 1970s, the use of Ding Shuangqi and phenformin was banned due to its toxic effects on patients with kidney disease, cardiovascular disease, and liver disease. Studies have found that phenformin and butyl bismuth can cause lactic acidosis, which is the reason for the ban on these two types of drugs in the US market in the 1970s. Metformin also has a risk of lactic acidosis, but its incidence is about 1/10 to 1/20 of phenformin.
New Use of Old Drugs
Although metformin is widely known for the treatment of type 2 diabetes, in recent decades, numerous studies have found that metformin can trigger anti-tumor activity in a variety of tumor types. In a pilot preclinical study, metformin showed a role in reducing tumor burden, delaying tumorigenesis, and prolonging lifespan in healthy non-diabetic mice. In 2005, Evans et al reported that patients with type 2 diabetes who took metformin had a lower likelihood of developing cancer. Similarly, researchers at the University of Alberta in Canada reported in 2006 that patients with type 2 diabetes who are taking metformin may have lower cancer-related mortality. This evidence has sparked a wave of research on various cancer patients. Metformin is expected to be useful in the treatment of various cancers including, but not limited to, skin cancer, uterine cancer, liver cancer, pancreatic cancer, colon cancer, lung cancer, ovarian cancer, breast cancer, head and neck cancer. It has been found that the potential anti-tumor properties of metformin are caused by its hypoglycemic function activating signaling pathways. Metformin partially inhibits mitochondrial respiratory chain complex I, leading to a decrease in hepatic gluconeogenesis; the resulting metabolic stress further leads to activation of the AMPK pathway, an important regulator of metabolism and cell growth – mammalian rapamycin targeting gene The (mTOR) pathway is inhibited. Because metabolism and cell growth are extremely important for cancer progression, metformin may have an effect on tumor prevention and treatment. In addition, studies have shown that cancer cells grow rapidly in high glucose and high insulin environments, and metformin may indirectly inhibit cancer growth by lowering glucose and insulin.
Recent studies on the treatment of metformin in head and neck squamous cell carcinoma (HNSCC) have shown that metformin can down-regulate mTOR pathway activity in head and neck squamous cell carcinoma and block the development and growth of HNSCC. Studies have found that metformin significantly reduces the size and number of carcinogen-induced oral tumor lesions and inhibits the spontaneous transformation to squamous cell carcinoma. These results indicate that the clinical use of metformin as a targeted chemopreventive drug for HNSCC is a new therapeutic approach.