Acarbose

Article Author:
Lindsey McIver
Article Editor:
Jayson Tripp
Updated:
10/27/2018 12:31:20 PM
PubMed Link:
Acarbose

Indications

Acarbose is FDA approved for the treatment of adults with type 2 diabetes mellitus as an adjunct to diet only or diet and exercise, depending on the patient's health status.

Based on the combined data of six placebo-controlled trials in patients with type 2 diabetes mellitus using acarbose as monotherapy, the following changes from baseline glycosylated hemoglobin (hemoglobin A1c) were noted by dose: 

  • Acarbose, 25 mg three times daily, decrease by 0.44
  • Acarbose, 50 mg three times daily, decrease  by 0.77
  • Acarbose, 100 mg three times daily, decrease by 0.74
  • Acarbose, 200 mg three times daily, decrease by 0.86
  • Acarbose, 300 mg three times daily, decrease by 1.00

Although the acarbose 300 mg three times daily regimen is superior to lower doses at lowering hemoglobin A1c, the approved maximum daily dose of acarbose is 100 mg three times daily. There is no statistically significant difference in hemoglobin A1c lowering between the 50 mg three times daily regimen, 100 mg three times daily regimen, and the 200 mg three times daily regimen.

Acarbose is not FDA approved for the treatment of type 1 diabetes mellitus; however, studies have evaluated the safety and efficacy in this patient population. In a study of 121 patients with type 1 diabetes mellitus, acarbose 50 mg three times daily for 2 weeks followed by 100 mg three times daily was found to significantly reduce 2-hour postprandial glucose. There were no differences between the placebo group and the acarbose group in hemoglobin A1c lowering or episodes of hypoglycemia.[1] In two subsequent, single center, placebo-controlled studies, 40 patients with type 1 diabetes mellitus were given metformin for 6 months after which metformin was replaced with acarbose. Acarbose was shown to significantly decrease the 2-hour postprandial blood glucose level when compared to baseline. When compared to metformin therapy, the acarbose therapy group was found to have a statistically significant decrease in low-density lipoprotein (calculated), triglycerides, and total cholesterol. Acarbose use also led to a statistically significant decrease in regular insulin use.[2]

Acarbose is not FDA approved for the treatment of prediabetes. However, it has been evaluated as a potential pharmacologic option for preventing the progression from prediabetes to type 2 diabetes mellitus. In a study of patients with impaired glucose tolerance tests, participants were randomized to acarbose 100 mg three times daily or placebo three times daily. Thirty-two percent of the acarbose group developed type 2 diabetes mellitus compared to 42% in the placebo group, resulting in a statistically significant hazard ratio of 0.75.[3]

The effect of acarbose on weight loss has been investigated. In an analysis of post-marketing data of 67,682 patients, acarbose was found to significantly decrease body weight, independent of baseline body weight. It also was found to significantly decrease fasting plasma glucose, postprandial glucose, hemoglobin A1c, and postprandial glucose excursion.[4]

Mechanism of Action

Acarbose is a complex oligosaccharide 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, resulting in a reduction of postprandial glucose.

Pharmacokinetics

Absorption

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

Metabolized

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

Excretion

The absorbed drug is excreted by the kidneys, and 51% of an oral dose is excreted in feces.

Administration

Acarbose is available as a 25 mg, 50 mg, or 100 mg oral tablet. It should be administered orally three times daily with the first bite of each meal. Initial dosing is 25 mg orally three times daily; however, starting with once-daily dosing may limit GI adverse effects. From 25 mg by mouth three 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 three times daily.

If the patient weighs less than 60 kg, the dose should not exceed 50 mg three times daily.

Use has not been studied in patients with renal dysfunction (serum creatinine greater than 2.0 mg/dL).

Safety and efficacy have not been evaluated in pediatric patients.

Safety of acarbose has not been established in pregnant patients.

Acarbose should not be used in nursing mothers.

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 should be monitored with other agents that affect blood glucose levels.

Adverse Effects

The most common adverse effects are GI symptoms, including flatulence, diarrhea, and abdominal pain. A high carbohydrate diet may worsen the GI adverse effects. GI symptoms tend to become reduced over the course of treatment.

Elevated serum transaminases have been noted during acarbose therapy. Elevations usually are asymptomatic and reversible once drug therapy has been stopped.

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

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

Contraindications

Acarbose use is contraindicated in patients with known hypersensitivity, diabetic ketoacidosis, liver cirrhosis, inflammatory bowel disease, or colonic ulceration. It also is 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 will be worsened by the increased gas formation in the intestine.

Monitoring

One- to 2-hour postprandial blood glucose levels and glycosylated hemoglobin should be monitored to assess efficacy. Serum transaminase levels should be checked every 3 months for the first year of therapy. The dose should be decreased or therapy discontinued if levels become elevated during therapy.

Toxicity

Overdose with acarbose will not cause hypoglycemia but may increase GI adverse effects. If overdose occurs, patients should not be given food or beverages that contain carbohydrates for 4 to 6 hours.

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



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      Contributes by Acarbose Wayne, NJ: Bayer HealthCare Pharmaceuticals Inc.; 2011.