Introduction of α-glucosidase inhibitors.📋📋📋

Diabetes is a very common chronic disease. With the development of social economy, the incidence of diabetes is getting higher and higher, and it has a younger trend. There are many types of hypoglycemic drugs. One of the common clinical hypoglycemic drugs is α-glucosidase inhibitors. How does an α-glucosidase inhibitor work and what is the difference between different α-glucosidase inhibitors?

Common α-glucosidase inhibitors.

Acarbose, voglibose and miglitol are common alpha-glucosidase inhibitors. 

• Acarbose is obtained by the direct extraction and isolation of secondary metabolites of Actinomycetes.
• Voglibose is obtained by modifying the structure of secondary metabolites of Actinomycetes.
• Miglitol is obtained by structural modification of secondary metabolites of Bacillus.

Acarbose

Voglibose

Miglitol

Mechanism of action of α-glucosidase inhibitors.

Monosaccharides (such as glucose, fructose, and galactose), disaccharides (such as sucrose, maltose), and polysaccharides (such as starch) are sugars in food. They are the most important energy substances in the human body. Small intestinal epithelial cells can directly absorb monosaccharides. Disaccharides and polysaccharides require α-glucosidase to hydrolyze them into monosaccharides for reabsorption. Therefore, when α-glucosidase activity is inhibited, the absorption of sugar can be reduced. α-glucosidase is a general term for carbohydrases such as sucrase, lactase, maltase, isomaltase, and alpha-critical dextrinase. α-glucosidase inhibitors are structurally similar to disaccharides or polysaccharides. It binds to α-glucosidase and inhibits its activity. It reduces the breakdown of these sugars into simple sugars, thereby reducing sugar absorption. It can effectively reduce glycosylated hemoglobin (HbA_1c) and the fluctuation of blood sugar after meals. 

Differences between acarbose, voglibose and migliitol.

The biggest difference between them is that they inhibit different carbohydrases. 

• Acarbose has the effect of inhibition mainly to glucoamylase, sucrase and pancreatic α-amylase.
• Voglibose mainly has inhibitory effects on maltase and sucrase and the inhibitory activity of acarbose on these two enzymes is much lower than it. Voglibose does not inhibit amylase. The starch in the food will be decomposed into disaccharides in the small intestine and relatively small starch enter to the large intestine. Therefore, gastrointestinal reactions such as bloating are less likely to occur with voglibose.
• Miglitol can inhibit all α-glucosidases. Among them, it has the highest ability of inhibition to glucoamylase and sucrase. The reason may be because its structure is similar to glucose, so it can bind to various α-glucosidases.

Dosage of acarbose, voglibose and migliitol.

• Acarbose should be taken as a whole tablet immediately before a meal or chewed with the first few bites during a meal. Its starting dose is 50mg each time, 3 times a day. Then it was gradually increased to 100 mg each time, 3 times a day. In individual cases, it can be increased to 200 mg each time, 3 times a day.
• Voglibose needs to be taken before meals and have meals immediately after taken it. Adults usually take 3 times a day, 0.2mg each time. If the treatment effect is not obvious, it can be increased to 0.3mg each time after sufficient observation.
• Miglitol needs to be taken before meals and have meals immediately after taken it. Its starting dose is 25mg each time, 3 times a day. Then it was gradually increased to 100 mg each time, 3 times a day. The maximum dosage can be increased to 200 mg each time, 3 times a day.

Differences in hypoglycemic ability.

All α-glucosidases inhibitors can effectively reduce 2-hour postprandial blood glucose and HbA_1c levels in patients with type 2 diabetes. Studies have indicated that their HbA_1c-lowering efficiency is voglitose < miglitol < acarbose. 

Precautions.

Acarbose and voglibose can damage the liver and should not be used in patients with severe liver dysfunction. When the patient's glomerular filtration rate is greater than or equal to 25ml/min, no adjustment of dosage is required. However, when the patient's glomerular filtration rate is less than 25ml/min, it is contraindicated.

Miglitol is not metabolized by the liver, so no dose adjustment is required in patients with hepatic insufficiency. Most miglitol is excreted by the kidneys, so patients with renal impairment will accumulate it in the body. However, no dose adjustment is required in patients with mild to moderate renal insufficiency. It is not recommended for patients with severe renal insufficiency.

Common adverse reactions of α-glucosidase inhibitors.

The pharmacological effects of α-glucosidase inhibitors can cause gastrointestinal reactions. In theory, after α-glucosidase inhibitors works, all the sugar is absorbed before it reaches the terminal ileum. But in reality, undigested sugars and starches are broken down by enzymes in the large intestine. It produces acids such as lactic acid and acetic acid. As a result, the pH in the intestine will drop and the osmotic pressure will increase. It causes diarrhea. The decomposition reaction also produces gases such as hydrogen and carbon dioxide, which can cause bloating. Therefore, α-glucosidase inhibitors are recommended to start with small doses. Patients will generally gradually tolerate it after 2 weeks of treatment.