Alpha-glucosidase inhibitors (AGI) are classic hypoglycemic agents and one of the recommended combination therapies in the 2020 edition of the Chinese T2DM prevention and treatment guidelines. AGI drugs have been widely used in China for nearly 30 years. Based on the increasingly rich clinical applications and scientific research evidence, the Endocrinology and Metabolism Branch of the Chinese Geriatrics Society organized domestic experts to compile the “Chinese Expert Consensus on the Clinical Application of Alpha-Glucosidase Inhibitors.” Here we summarize the main recommendations for reference and learning.
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Mechanism of Action
Alpha-glucosidase is a type of hydrolase, mainly including sucrase, maltase, isomaltase, and lactase, which can convert oligosaccharides into glucose.AGI can simulate polysaccharides in the body, reversibly competing to bind with alpha-glucosidase on the intestinal villi, with a binding capacity far exceeding that of polysaccharides, inhibiting carbohydrate breakdown, reducing glucose production and absorption, and slowing postprandial increases. AGI drugs are suitable for patients whose postprandial blood glucose (PPG) increases due to carbohydrates in food.
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Other Effects
1. Adjusting Incretin SecretionPrimarily manifested as an increase in postprandial GLP-1 secretion, potentially through: (1) Altering the distribution of carbohydrates in different parts of the intestine. After using AGI, carbohydrates in the upper small intestine cannot be fully absorbed, leading to an increase in carbohydrates reaching the lower small intestine, stimulating L cells to secrete more GLP-1. (2) Inhibiting DPP-4 activity.2. Adjusting Gut MicrobiotaAGI can increase carbohydrates in the distal small intestine, thereby altering the fermentation of intestinal microorganisms, affecting the composition and function of gut microbiota, promoting the growth of probiotics, inhibiting the proliferation of harmful bacteria, helping to maintain intestinal microecological balance, and improving metabolic health and immune function.3. Improving Insulin Resistance (IR)Studies show that for patients with diabetes and abnormal glucose tolerance, AGI reduces PPG and postprandial insulin, thereby alleviating hyperinsulinemia. Its mechanisms include reducing the secretion of inflammatory factors and increasing intestinal bile acid secretion through various pathways.4. Weight LossVoglibose has little effect on weight; Acarbose and Miglitol have a slight weight loss effect.5. Improving Oxidative StressPPG fluctuations are a major cause of oxidative stress. AGI can reduce oxidative stress by lowering PPG and increasing blood glucose stability. Additionally, Miglitol can inhibit oxidative stress by activating AMP-activated protein kinase and increasing nitric oxide synthase activity.6. Reducing Cardiovascular Events (MACE) in Prediabetic and Diabetic PatientsThe main mechanisms include that AGI drugs can reduce the hemodynamic and autonomic nervous system effects of blood glucose fluctuations in diabetic patients, reduce the progression of atherosclerosis, activate GLP-1 receptors, open mitochondrial ATP-sensitive potassium channels, prevent hydroxyl radical production, and reduce the production of inflammatory factors such as monocyte chemotactic protein 1 and soluble adhesion molecule sE-selectin.7. Other Hypoglycemic Effects (1) Improving Metabolically Associated Fatty Liver Disease (MAFLD) (2) Potential anti-COVID-19 effects (3) Inhibiting melanin formation
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Types and Usage
Currently, AGI drugs available in China include Acarbose, Miglitol, and Voglibose.
The AGI drugs currently marketed in China mainly include conventional tablets and orally disintegrating tablets. Among them, Miglitol orally disintegrating tablets are the first and currently only AGI orally disintegrating tablet new dosage form, which is bioequivalent to Miglitol tablets.>> Consensus Recommendations:
- AGI drugs can be used to prevent the progression of prediabetic patients to diabetes, with clear and reliable efficacy.
- In newly diagnosed and untreated T2DM patients in China, the efficacy of AGI monotherapy is comparable to that of Metformin and can be one of the first-choice medications.
- Due to AGI’s unique mechanism of action, it can be combined with insulin, Metformin, sulfonylurea insulin secretagogues, DPP-4 inhibitors, and other classes of hypoglycemic drugs to better control blood glucose, reduce blood glucose fluctuations, and minimize hypoglycemic events.
- AGI drugs, especially Miglitol, can effectively treat functional hypoglycemia and can be used for dumping syndrome, reactive hypoglycemia, etc.
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Adverse Reactions and Management
(1) Common adverse reactions include gastrointestinal reactions (bloating, gas, diarrhea, etc.). Starting with a small dose and gradually increasing is an effective method to reduce adverse reactions. (2) AGI may induce rare colonic gas accumulation in patients with underlying diseases (liver cirrhosis, emphysema, malnutrition, use of glucocorticoids, etc.). Related pathological changes can completely disappear after discontinuation. (3) Acarbose and Voglibose can cause elevated transaminases, requiring regular monitoring of liver function. (4) AGI used alone will not cause hypoglycemia; if hypoglycemia occurs during treatment, glucose or honey should be used to correct it, as sucrose or starchy foods are less effective in correcting hypoglycemia.
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Contraindications
Patients with acute diabetic complications such as DKA;Patients allergic to the drug components;Patients whose conditions may worsen due to intestinal gas accumulation, such as inflammatory bowel disease, colonic ulcers, intestinal obstruction, and severe abdominal hernias;Patients with chronic intestinal diseases associated with digestive and absorption disorders;Individuals under 18 years of age;Pregnant or breastfeeding patients, as all three AGI drugs can enter breast milk in small amounts, and there are no safety studies in pregnant patients.
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Other Precautions
AGI drugs should be taken immediately before meals containing carbohydrates.It is not recommended for patients with eGFR < 25 mL/(min·1.73m²) to use AGI.Different AGIs have different liver safety profiles; Miglitol does not require routine monitoring of liver function.Antibiotic use and concomitant medications can affect AGI efficacy, so caution is needed when using them.✩ This article is for reference only for healthcare professionals.The article was first published on the professional platform under Dingxiangyuan: Dingxiangyuan Endocrine Time Planning | Dai DongjunSubmission address | [email protected]Cover image | Zcool HailuoReferences:Chinese Expert Consensus on the Clinical Application of Alpha-Glucosidase InhibitorsConsensus