What Are Biguanides?

Metformin, (1) Metformin tablets are best treated with simple diet control and physical exercise to treat ineffective type 2 diabetes, especially obese type 2 diabetes. (2) This product can be combined with insulin to reduce the amount of insulin and prevent hypoglycemia. (3) It can be used in combination with sulfonylurea hypoglycemic agents and has a synergistic effect.

Metformin, (1) Metformin tablets are best treated with simple diet control and physical exercise to treat ineffective type 2 diabetes, especially obese type 2 diabetes. (2) This product can be combined with insulin to reduce the amount of insulin and prevent hypoglycemia. (3) It can be used in combination with sulfonylurea hypoglycemic agents and has a synergistic effect.

In 2019, Cancer Cell recently published an article where researchers found that metformin use in fasting could significantly inhibit tumor growth and suggested that the PP2A-GSK3-MCL-1 pathway may be a new target for tumor treatment. ^[1]

Its hydrochloride is usually white crystal or crystalline powder; it is odorless. Soluble in water, soluble in methanol, slightly soluble in ethanol, insoluble in chloroform, acetonitrile or ether.

It is a biguanide oral hypoglycemic agent with a weaker effect than phenformin. The absorption rate after oral administration is only 50%. tmax is about 2 hours and does not bind to plasma proteins in plasma. Almost all are excreted by the urine, the first phase t1 / 2 is about 3 hours, the second phase t1 / 2 is about 12-14 hours, and the hypoglycemic effect can last 8 hours.

(1) Metformin tablets are best treated with simple diet control and physical exercise to treat ineffective type 2 diabetes, especially obese type 2 diabetes. (2) This product can be combined with insulin to reduce the amount of insulin and prevent hypoglycemia. (3) It can be used in combination with sulfonylurea hypoglycemic agents and has a synergistic effect.

Due to different dosage forms and specifications, please read the drug instructions carefully or follow the doctor's advice.

(1) Occasionally nausea, vomiting, diarrhea, abdominal pain, bloating, indigestion, and fatigue. (2) Occasionally fatigue, weight loss, headache, dizziness, abnormal taste, rash, chills, flu-like symptoms, palpitations, flushing, etc. (3) Rare lactic acidosis is manifested by vomiting, abdominal pain, excessive ventilation, and disturbance of consciousness.

People who are allergic to this product, diabetic ketoacidosis, liver and kidney insufficiency (serum creatinine exceeds 1.5 mg / dl), pulmonary insufficiency, heart failure, acute myocardial infarction, severe infection and trauma, major surgery and clinical hypotension And hypoxia, alcoholism, vitamin B12, folic acid deficiency, those with severe diabetic nephropathy, diabetic fundus disease, pregnant and lactating women are prohibited.

(1) People with a previous history of lactic acidosis and elderly patients should use it with caution. As the accumulation of this product may cause lactic acidosis, once it occurs, it will lead to life-threatening. Therefore, renal function should be monitored and the minimum effective amount should be given to reduce lactic acidosis. Risk occurs. (2) Stress states such as fever, coma, infection, etc. When taking surgery or using iodine-containing contrast agents for examination, you should temporarily stop taking this product, because it may cause acute renal function deterioration. (3) When combined with sulfonylurea drugs and insulin, it can cause hypoglycemia. Avoid drinking alcohol when taking this product. Easy to cause hypoglycemia or lactic acidosis. Use with caution in patients with poor liver function. (4) This product can interfere with the absorption of vitamin B12, it is recommended to monitor blood.

Tablets, capsules, enteric (tablets, capsules): 0.25g, 0.5g

[Identification] (1) Take about 10mg of this product, add 10ml of water to dissolve, add 10% sodium nitroso ferricyanide solution-potassium ferricyanide test solution-10% sodium hydroxide solution (mixed in equal volumes, and leave for 20 minutes Use) 10ml, the solution is red within 3 minutes. (2) The infrared absorption spectrum of this product should be consistent with the control spectrum (spectrum set 631). (3) Identification reaction of this product showing chloride (Appendix III). [Inspection] Take this product, weigh it accurately, add mobile phase to dissolve and quantitatively dilute to make a solution containing about 5mg per 1ml.

In 2019, Cancer Cell recently published an article where researchers found that metformin use in fasting could significantly inhibit tumor growth and suggested that the PP2A-GSK3-MCL-1 pathway may be a new target for tumor treatment.

Studies have shown that calorie restriction leads to insufficient energy supply, which reduces the body's metabolism and so on, and exerts anti-cancer effects. The study found that intermittent fasting can not only regulate the metabolism in the body and increase the effect of chemotherapy, but also protect patients from the toxic and side effects of chemotherapy and help clinical treatment. In addition, researchers combined intermittent fasting with metformin and explored the therapeutic potential of tumors.
The researchers divided experimental mice inoculated with human colon cancer cells into five groups, two of which were fed for 24 hours, and the other three were intermittently fasted on a 24-hour cycle. The normal feeding group and the intermittent fasting group were treated with metformin or placebo, respectively. The results of the study found that metformin significantly inhibited tumor growth only during treatment of fasting-induced hypoglycemia. In addition, the researchers found that tumor cells are sensitive to metformin only in a low-sugar environment, suggesting that metformin will act as an anti-tumor in a low-sugar environment.

Under low glucose / metformin treatment, glycogen synthase kinase 3 (GSK3) is over-activated in cells and promotes apoptosis. After inhibiting this enzyme, the effect of low glucose / metformin on tumor growth is reduced. Further mechanistic studies found that the synergistic antitumor effect of the metformin / hypoglycemic combination is mediated by the activation of glycogen synthase kinase 3 (GSK3) downstream of PP2A, leading to a decrease in the expression of pro-survivin MCL-1 and cell death in tumor cells. The specific activation of the PP2A-GSK3 axis is the sum of metformin-induced CIP2A inhibition. The PP2A inhibitor and the PP2A regulatory subunit B56 are up-regulated by low glucose, resulting in the PP2A-B56 complex with high affinity activity.
The results of this study indicate that the discovery of the PP2A-GSK3-MCL-1 pathway may be a target for the treatment of tumors, but the safety of metformin / low glucose combined therapy in patients needs further experimental verification. ^[1]