Acarbose

Acarbose is an alpha-glucosidase inhibitor that lowers post-meal blood sugar and insulin spikes in Type 2 Diabetes by blocking intestinal enzymes (such as alpha-amylase and sucrase) from breaking down complex carbohydrates into absorbable simple sugars. It is used alongside diet, exercise, and other medications. However, it is rarely prescribed today due to its limited impact on long-term blood sugar levels ($A1c$), cumbersome thrice-daily dosing requirement, and significant gastrointestinal side effects.

Acarbose is an alpha-glucosidase inhibitor used in adjunctly with diet and exercise for the management of glycemic control in patients with type 2 diabetes mellitus.

Acarbose is indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus.

• Type 2 Diabetes Mellitus

Acarbose is a complex oligosaccharide that competitively inhibits the ability of brush-border alpha-glucosidase enzymes to break down ingested carbohydrates into absorbable monosaccharides, reducing carbohydrate absorption and subsequent postprandial insulin levels. Acarbose requires the co-administration of carbohydrates in order to exert its therapeutic effect, and as such should be taken with the first bite of a meal three times daily.

Given its mechanism of action, acarbose in isolation poses little risk of contributing to hypoglycemia - this risk is more pronounced, however, when acarbose is used in conjunction with other antidiabetic therapies (e.g. sulfonylureas, insulin). Patients maintained on acarbose in addition to other antidiabetic agents should be aware of the symptoms and risks of hypoglycemia and how to treat hypoglycemic episodes. There have been rare post-marketing reports of the development of pneumatosis cystoides intestinalis following treatment with alpha-glucosidase inhibitors - patients experiencing significant diarrhea/constipation, mucus discharge, and/or rectal bleeding should be investigated and, if pneumatosis cystoides intestinalis is suspected, should discontinue therapy.

Alpha-glucosidase enzymes are located in the brush-border of the intestinal mucosa and serve to metabolize oligo-, tri-, and disaccharides (e.g. sucrose) into smaller monosaccharides (e.g. glucose, fructose) which are more readily absorbed. These work in conjunction with pancreatic alpha-amylase, an enzyme found in the intestinal lumen that hydrolyzes complex starches to oligosaccharides.

Acarbose is a complex oligosaccharide that competitively and reversibly inhibits both pancreatic alpha-amylase and membrane-bound alpha-glucosidases - of the alpha-glucosidases, inhibitory potency appears to follow a rank order of glucoamylase > sucrase > maltase > isomaltase. By preventing the metabolism and subsequent absorption of dietary carbohydrates, acarbose reduces postprandial blood glucose and insulin levels.

The oral bioavailability of acarbose is extremely minimal, with less than 1-2% of orally administered parent drug reaching the systemic circulation. Despite this, approximately 35% of the total radioactivity from a radiolabeled and orally administered dose of acarbose reaches the systemic circulation, with peak plasma radioactivity occurring 14-24 hours after dosing - this delay is likely reflective of metabolite absorption rather than absorption of the parent drug. As acarbose is intended to work within the gut, its minimal degree of oral bioavailability is therapeutically desirable.

As only 1-2% of an orally administered dose is absorbed into the circulation, acarbose is unlikely to be subject to clinically relevant protein binding.

Roughly half of an orally administered dose is excreted in the feces within 96 hours of administration. What little drug material is absorbed into the systemic circulation (approximately 34% of an orally administered dose) is excreted primarily by the kidneys, suggesting renal excretion would be a significant route of elimination if the parent drug was more readily absorbed - this is further supported by data in which approximately 89% of an intravenously administered dose of acarbose was excreted in the urine as active drug (in comparison to 7

In healthy volunteers, the plasma elimination half-life of acarbose is approximately 2 hours.

The symptoms of acarbose overdose are likely to be consistent with its adverse effect profile and may therefore include significant gastrointestinal (GI) symptoms (flatulence, distension, etc), although an overdose on an empty stomach (i.e. when not co-administered with food) is less likely to result in these GI symptoms. In the event of an overdose, patients should be instructed to avoid carbohydrate-containing foods for 4-6 hours following administration as these can precipitate the aforementioned GI symptoms.

• Take with food. Each dose should be taken with the first bite of a main meal.