The diabetes guidelines recommend a course of treatment for type 2 diabetes that includes:
Major oral hypoglycemic agents
According to the different mechanism of action, they are divided into insulin secreting agents (sulfonylureas, glanide) , biguanides, Thiazolidinedione insulin sensitizers, α-glucosidase inhibitors, and dibasic peptidase-iv (VDPP-IV) inhibitors, etc. . Drug selection should be based on two major pathophysiological changes in type 2 diabetes: insulin resistance and impaired insulin secretion. In addition, the characteristics of blood glucose fluctuation, age, weight, important organ function and so on are also important factors to be taken into account in drug selection. In order to increase the curative effect and reduce the incidence of adverse reactions, drugs with complementary mechanisms should be used in combination therapy.
1. Biguanides: these drugs reduce glycogen production in the liver, promote the uptake of glucose by muscles and other peripheral tissues, accelerate glycolysis of sugars, and reduce the absorption of sugars in the intestine. It has the effect of reducing fat and uric acid. Suitable for type 2 diabetes, especially obese people should be the first choice of drugs. Preparations contain 1 phenformin; 2 metformin. By far the most common is metformin. A rare side effect of biguanides is lactic acidosis. There are very few metformin, biguanides are contraindicated in patients with renal insufficiency (serum creatinine levels > 1.5 mg/dL in males and 1.4 mg/dL in females or glomerular filtration rate < 60 ml/min/1.73 m2) , liver dysfunction, severe infection, hypoxia or major surgery. The use of iodinated contrast media should be temporarily suspended during metformin examination. The main side effect of metformin is gastrointestinal reaction. Gastrointestinal symptoms in 10% of patients, can have abdominal discomfort, anorexia, nausea, diarrhea, occasionally dry mouth or metal taste.
Diabetes guidelines drawn up by many countries and international organizations recommend metformin as a first line drug for controlling high blood sugar in patients with type 2 diabetes and as a base drug for combination therapy. Clinical trials have shown that metformin can reduce HbA1c by 1-2% and lead to weight loss. The UKPDS trial has also been shown to reduce cardiovascular events and deaths in obese patients with type 2 diabetes, according to the metformin.
2. Sulfonylurea: this kind of medicine mainly acts on the islet B cell surface sulfonylurea receptor, promotes the insulin secretion. Applicable to islet B cells are still functional, and no serious liver, kidney dysfunction in diabetic patients with sulfonylureas if improper use can lead to hypoglycemia, especially in elderly patients and liver, kidney dysfunction; Sulfonylureas can also cause weight gain. Clinical trials have shown that sulfonylureas can reduce HbA1c by 1%-2% , which is the main drug for controlling hyperglycemia in patients with type 2 diabetes.
Sulfonylureas include tolbutamide; glibenclamide; gliclazide; Alexander Vyssotsky; Gliquidone; Glimepiride, et al. . There are also some sustained-release and controlled-release dosage forms of sulfonylurea drugs, such as gliclazide sustained-release tablets, Alexander Vyssotsky controlled-release tablets, etc. .
3. Benzoic acid derivatives as secretagogues: including repaglinide and nateglinide. This kind of drugs can reduce postprandial blood glucose by stimulating the early secretion of insulin, which has the characteristics of fast absorption, quick onset and short acting time, and can reduce HbA1c by 0.3%-1.5% . These drugs should be taken immediately before meals and can be used alone or in combination with other hypoglycemic agents (except sulfonylureas) . The common side effects of glibenclamide are hypoglycemia and weight gain, but the frequency and degree of hypoglycemia are less than those of sulfonylureas.
4. α-glucosidase inhibitor: can selectively act on the brush border of small intestinal mucosa glucosidase, inhibit the decomposition of polysaccharides and sucrose into glucose, slow carbohydrate digestion, reduce glucose absorption. Can improve the postprandial blood sugar peak. They include acarbose, Voglibose, etc. . α-glucosidase inhibitors can decrease HbAlc by 0.5%-0.8% . The common adverse reaction of α-glycosidase inhibitors is gastrointestinal reaction.
5. Thiazolidinedione (insulin sensitizer) : by activating nuclear receptor PPAR γ, the sensitivity of peripheral tissues to insulin is enhanced, such as increasing the absorption and transport of glucose in adipose tissue, inhibiting the release of plasma FFA, and inhibiting the release of liver sugar, strengthens the skeletal muscle to synthesize the glucose and so on to reduce the insulin resistance. It is suitable for type 2 diabetes mellitus with insulin resistance. Clinical trials have shown that Thiazolidinedione can reduce HbA1c by between 1.0% and 1.5% . The main categories include 1 Rosiglitazone; 2 pioglitazone. Weight gain and edema are common side effects of Thiazolidinedione. The use of Thiazolidinedione was also associated with an increased risk of fractures and heart failure.
Note: About Rosiglitazone’s use:
The safety of Rosiglitazone is controversial, and its use is severely limited in China. For people with diabetes who have not used Rosiglitazone and its combination therapy, the goal of blood sugar control should only be achieved if no other hypoglycemic agent is used or if no other hypoglycemic agent can be used, to consider using Rosiglitazone and its compound. Patients who are already taking Rosiglitazone and its combination should be assessed for cardiovascular risk and should only continue to take the drug after weighing the benefits and risks.
6. Dipeptidyl peptidase-VI (DPP-VI) inhibitors: DPP-IV inhibitors decrease the inactivation of GLP-1 and increase the level of Glp-1 in vivo by inhibiting dipeptidyl peptidase-IV. GLP-1 enhances insulin secretion and inhibits Glucagon secretion in a glucose concentration-dependent manner. A clinical trial involving Chinese patients with type 2 diabetes showed that sitagliptin reduced HbA1c by 1.0% . The DPP-IV inhibitors currently listed in China are sitagliptin and saxagliptin.
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