Alpha Glucosidase Inhibitors

Alpha-glucosidase inhibitors (AGIs) are a class of drugs that are used in the treatment of type 2 diabetes mellitus, alone or combined with other antidiabetic drugs. They may also be used in patients with impaired glucose tolerance and delay the occurrence of type 2 diabetes mellitus in these patients. They are particularly useful for patients who are at risk of hypoglycemia or lactic acidosis, and thus, are not suitable candidates for other antidiabetic drugs such as sulfonylureas and metformin.[1][2][3][4]                      

The FDA approves AGIs for the treatment of type 2 diabetes mellitus. They have shown some benefit in type 1 diabetes mellitus and gestational diabetes mellitus but are not FDA-approved for these indications. Acarbose has shown to decrease body weight in a worldwide observational study.[5]

AGIs are particularly useful for reducing postprandial hyperglycemia. They modestly decrease glycosylated hemoglobin levels and also reduce postprandial insulin concentration. Compared with oral antihyperglycemic drugs, they also reduce glucose variability throughout the day. They, however, do not affect fasting insulin and serum triglyceride concentrations. Controlling postprandial hyperglycemia is essential as it correlates with the development of microvascular complications and increases the risk for the development of cardiovascular diseases. This link between postprandial blood glucose (PPG) and long-term diabetic complications are even stronger than that of fasting hyperglycemia.[6][7]

Acarbose has been shown to increase life expectancy in patients with type 2 diabetes mellitus and reduces the risk of development of cardiovascular events in patients with impaired glucose tolerance. It has proven efficacy in stabilizing carotid plaques; by reducing hyperglycemia, it counters oxidative stress and endothelial dysfunction.[8][9]

AGIs inhibit the absorption of carbohydrates from the small intestine. They competitively inhibit enzymes that convert complex non-absorbable carbohydrates into simple absorbable carbohydrates. These enzymes include glucoamylase, sucrase, maltase, and isomaltase. By delaying carbohydrate absorption, they reduce the rise in postprandial blood glucose concentrations by about 3 mmol/l. 

Acarbose is the most commonly used drug of this class, and also the most widely studied one. Others include voglibose and miglitol. Acarbose inhibits alpha-amylase, maltase, sucrase, and dextranase, and is most effective against glucoamylase. It does not affect lactase, which is a beta-glucosidase. Acarbose and voglibose (not FDA-approved in the USA) are poorly absorbed from the gut, have low bioavailability, and are excreted in the stool. Miglitol, on the other hand, is absorbed from the gut completely and is excreted through the renal route. Acarbose undergoes metabolism in the colon, while miglitol and voglibose have no metabolites.[1][10][3]

AGIs are administered orally. They should be taken three times a day with the first bite of each meal. The general recommendation is to always start with a lower dose, both to reduce the frequency of adverse effects and to achieve the desired dose for optimal glycemic control. Acarbose should be started at a dose of 25 mg three times daily, titrating thereafter every 4 to 8 weeks, with the maximum dose being 100 mg three times a day. For voglibose, the recommended initial dose is 0.2 mg three times daily, which can be increased up to 0.3 mg three times daily. For miglitol, the initial dose is 25 mg three times daily, and the maximum dose is 100 mg thrice a day.[1]

Safety of AGIs has not been established in pediatric and pregnant patients, warranting caution if their use is indicated in these populations.

The effectiveness of AGIs is affected by the quantity of complex carbohydrate in the diet. A carbohydrate-rich diet also increases the severity of gastrointestinal side effects.[11]

Gastrointestinal disturbances are the most commonly reported side effects of AGIs. These result from the degradation of undigested carbohydrates by bacteria in the colon, which causes excessive gas formation. Flatulence is the most commonly reported side effect, appearing in about 78% of the cases. Diarrhea and abdominal pain may also occur. The use of acarbose (but not other AGIs) has potential links with hepatitis in some instances. These abate with time, and their severity can be further reduced by starting with a low dose. A carbohydrate-rich diet can precipitate these adverse effects.[1][12]

AGIs are contraindicated in any of the conditions that can worsen due to excess gas formation in the gut. It is also contraindicated in patients who are either suffering from intestinal obstruction or are at risk of intestinal obstruction. Other contraindications include diabetic ketoacidosis, chronic intestinal disease, colonic ulceration, inflammatory bowel disease, and known hypersensitivity to this group of drugs.[1]