Diabetes is a disease characterized by continuous high blood glucose levels. The major conditions of diabetes are carbohydrate metabolism abnormality and lipid metabolism abnormality, and systemic complications thereof grow worse due to blood flow disturbance caused by high blood glucose levels and due to a decrease in sugar utilization. Such diabetic conditions are caused by the deficiency of hormone insulin, which regulates carbohydrate and lipid metabolisms, or insulin resistance. Diabetes caused by insulin resistance is called “type 2 diabetes”.
Type 2 diabetes is induced from a state in which insulin does not exhibit a function of transporting glucose into cells due to the decreases of insulin receptors or due to the deficiency of signal transduction pathways through insulin receptors, i.e., a condition in which the body becomes resistant to insulin secreted from the pancreas. In other words, Type 2 diabetes suffers from direct destruction of blood vessels and severe metabolic syndromes due to hyperinsulinemia.
Many kinds of anti-diabetic drugs have been used to treat type 2 diabetes. However, the drugs excluding biguanide metformin do not show satisfactory effects on the prevention of important complications including visual loss, heart failure, stroke, renal failure, peripheral neuropathy, foot ulcer and the like, although they are somewhat effective in lowering blood glucose levels. For example, sulfonylurea-based drugs, which act to lower blood glucose levels by enforcing insulin to be secreted from the pancreas, have problems in that their effects rapidly disappear and they induce abnormal lipid metabolism, thereby promoting arteriosclerosis, increasing bodyweight and causing brain injuries due to low blood glucose levels. Moreover, as glitazone-based drugs give an effect only on insulin resistance mainly in adipose tissues, they must be used in combination with metformin. In addition, close attention should be paid to the use of the glitazone-based drugs because the drugs may cause side effects such as retinal vascular occlusion.
Metformin, the only drug that has the same effect as that of insulin, does not cause a low blood glucose problem, solves a problem of insulin resistance in adipose, liver and muscular tissues, and exhibits improved blood glucose level- and glycosylated hemoglobin level-lowering actions. Particularly, it has been reported that metformin activates AMPK (AMP-activated protein kinase), and thus has various effects of normalizing blood glucose levels, enhancing lipid conditions, normalizing irregular menstruation, ovulation and pregnancy, treating fatty liver, and even preventing cancers.
Metformin is generally administered three times a day, and its dosage per one administration is more than about 500 mg. Thus, in order to make sustained-release tablets to be administered once a day, tablets containing at least 1500 mg of metformin are required. However, it is difficult to take such tablets due to its very large size. In addition, currently commercially available sustained-release tablets contain only about 750 mg of metformin per one tablet, and thus, at least two tablets should be administered once at a 24 hr interval. Therefore, there exists a need to develop preparations which exhibit improved blood glucose level- and lipid level-lowering effects, thereby being capable of reducing its daily dosage.
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