Acarbose

Mechanism of Action

Acarbose is a complex oligosaccharide (see Image. Acarbose Chemical Structure) that acts as a competitive, reversible inhibitor of pancreatic alpha-amylase and membrane-bound intestinal alpha-glucoside hydrolase. Pancreatic alpha-amylase hydrolyzes complex carbohydrates to oligosaccharides in the small intestine. Intestinal alpha-glucosidase hydrolase breaks down oligosaccharides, trisaccharides, and disaccharides (sucrose, maltose) to monosaccharides (glucose, fructose) in the brush border of the small intestine. By delaying the digestion of carbohydrates, acarbose slows glucose absorption, reducing postprandial glucose blood concentrations.

Pharmacokinetics

Absorption

Acarbose acts locally in the gastrointestinal (GI) tract with low systemic bioavailability (less than 2% gets absorbed as the active drug, and 35% as metabolites).

Metabolism

Acarbose is metabolized in the GI tract by intestinal bacteria and digestive enzymes.

Elimination

The kidneys filter the absorbed drug, and 51% of an oral dose gets eliminated in feces.

Administration

Dosage Forms

Acarbose is available as a 25 mg, 50 mg, or 100 mg oral tablet and should be administered orally 3 times daily with the first bite of each meal.

Adult Dosing

Initial dosing is 25 mg orally, 3 times daily. However, starting with once-daily dosing may limit GI adverse effects. From 25 mg by mouth, 3 times daily, the dose can be titrated every 4 to 8 weeks to reach desired glycemic control while limiting GI adverse effects. The maximum daily dose is 100 mg, 3 times daily.

• If the patient weighs less than 60 kg, the dose should not exceed 50 mg, 3 times daily.
• Patients with renal dysfunction (serum creatinine greater than 2.0 mg/dL) have not been studied.
• Safety and efficacy have not undergone evaluation in pediatric patients.
• Studies have not established the safety of acarbose in pregnant patients.
• Nursing mothers should not use acarbose.

Gruden S. et al conducted a study on 67 obese middle-aged Caucasian men with treatment regimens that included orlistat and acarbose modified-release oral capsules to determine the safety of this experimental dosage form.[12] Three dosages were examined: 60/20, 90/30, and 120/40 mg orlistat/mg acarbose, respectively. The 3-dose combinations were found to be well-tolerated. The combination of orlistat and acarbose could help better control weight in patients with diabetes mellitus.

Mabate B. et al conducted in vitro research on combining fucoidan and acarbose to treat diabetes mellitus.[13] Fucoidan is a natural product that, when combined with acarbose, produces about 70% inhibition of alpha-glucosidase. This combination could decrease the dose of acarbose needed to lower plasma glucose and thus reduce the side effects of acarbose.

Drug-Drug Interactions

• Acarbose may decrease the bioavailability of digoxin and valproic acid.
• Acarbose may increase hypoglycemic risk when combined with other anti-diabetic agents that cause hypoglycemia.
• Digestive enzymes, including amylase, lipase, and protease, may decrease the effectiveness of acarbose.
• Therapy requires monitoring with other agents that affect blood glucose concentrations.

Adverse Effects

The most common adverse effects are GI symptoms, including flatulence, diarrhea, and abdominal pain. A high carbohydrate diet may worsen the adverse effects on the GI tract. GI symptoms tend to become reduced throughout treatment. Adherence to acarbose pharmacotherapy can be a problem because of side effects.[14]

Elevated serum transaminases may occur during acarbose therapy. Elevations are usually asymptomatic and reversible once drug therapy is discontinued.

Hypoglycemia should not occur with acarbose monotherapy. However, the therapy can increase the risk of hypoglycemia when used with antidiabetic agents that cause hypoglycemia, such as sulfonylureas or insulins.

Post-marketing reports include cases where there were rare occurrences of pneumatosis and cystoides intestinalis with alpha-glucosidase inhibitor use.

Jiang L et al conducted a retrospective cross-sectional study on muscle mass and function in patients with type 2 diabetes mellitus who were on plasma glucose-lowering therapy.[15] Acarbose decreased skeletal muscle index, handgrip strength, and gait speed the most compared with drug-naïve patients and patients taking insulin, metformin, and sulfonylureas monotherapy.

Contraindications

Acarbose use is contraindicated in patients with known hypersensitivity, diabetic ketoacidosis, liver cirrhosis, inflammatory bowel disease, or colonic ulceration. This medication is also contraindicated in patients with intestinal obstruction or those predisposed to intestinal obstruction; patients with chronic intestinal disease, including those who have issues with digestion or absorption; or conditions that the increased gas formation in the intestine will worsen.

Monitoring

One to 2-hour postprandial blood glucose concentrations and glycosylated hemoglobin require monitoring to assess efficacy. Serum transaminase concentrations should be checked every 3 months for the first year of therapy. The clinician should decrease the dose or discontinue therapy if concentrations become elevated during treatment.

Toxicity

Overdose with acarbose will not cause hypoglycemia but may increase GI adverse effects. Patients should not have food or beverages that contain carbohydrates for 4 to 6 hours if an overdose occurs.

If a patient experiences hypoglycemia while taking acarbose in combination with other antidiabetic medications, the patient should receive instructions to use glucose (gel, tablets, etc). Acarbose will prevent the breakdown of sucrose (table sugar) and delay glucose absorption, failing to correct hypoglycemia quickly. Severe hypoglycemia may require intravenous glucose or intramuscular glucagon administration.

Enhancing Healthcare Team Outcomes

Acarbose is a commonly used medication for managing type 2 diabetes mellitus. While the drug is helpful, it is not a highly effective agent when used as monotherapy. Because the drug works in the gastrointestinal system, the most common adverse effects are gastrointestinal upset/bloating. Hence, the prescribing clinicians (MD, DO, NP, PA), nurses (especially certified diabetes educators), and pharmacists must educate the patient on how to use the drug. Further, patients should receive counsel to avoid cola beverages, as the adverse abdominal symptoms may worsen.

While hypoglycemia is extremely rare with this agent, one should consider other antidiabetic drugs as the cause if it occurs. The patient should be treated for hypoglycemia and then counseled on preventing further low-sugar episodes. Only through patient education can the side effects be limited, and as with any medication, acarbose management is best by an interprofessional healthcare team across various disciplines, who engage in open communication with other team members regarding any changes in the patient's status so appropriate corrective action can be taken if necessary.