Continuing Education Activity

Type 2 diabetes mellitus is a growing concern worldwide, and in the USA in particular, with clinicians encountering the condition more frequently and at younger ages than in previous years. Acarbose is approved for treating adults with type 2 diabetes mellitus as an adjunct to diet only or diet and exercise, depending on the patient's health status. This activity outlines the indications, contraindications, interactions, monitoring, and other therapeutic information pertinent to members of an interprofessional team in caring for patients using acarbose therapy.

Objectives:

• Identify the mechanism of action of acarbose.
• Summarize the potential adverse effects of acarbose.
• Describe appropriate monitoring for acarbose therapy.
• Review interprofessional team strategies for improving care coordination and communication when using acarbose to improve patient outcomes for glucose control.

Indications

Acarbose is FDA approved for treating 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, researchers noted the following changes from baseline glycosylated hemoglobin (hemoglobin A1c) by dose: 

• Acarbose, 25 mg three times daily, decreased by 0.44
• Acarbose, 50 mg three times daily, decreased  by 0.77
• Acarbose, 100 mg three times daily, decreased by 0.74
• Acarbose, 200 mg three times daily, decreased by 0.86
• Acarbose, 300 mg three times daily, decreased 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 treating type 1 diabetes mellitus; however, studies have evaluated its 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 two weeks, followed by 100 mg three times daily, was found to reduce 2-hour postprandial glucose significantly. 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 six months after acarbose replaced metformin. The research demonstrated acarbose significantly decreased the 2-hour postprandial blood glucose concentration compared to baseline. Compared to metformin therapy, the acarbose therapy group showed a statistically significant decrease in low-density lipoprotein (calculated), triglycerides, and total cholesterol. Acarbose use also led to a statistically significant reduction in regular insulin use.[2]

Acarbose is not FDA-approved for the treatment of prediabetes. Acarbose has also undergone evaluation 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 also been a target of research. In an analysis of post-marketing data of 67,682 patients, the data revealed acarbose to decrease body weight significantly, independent of baseline body weight. It also was found to significantly reduce fasting plasma glucose, postprandial glucose, hemoglobin A1c, and postprandial glucose concentrations.[4]

Li J. et al. found that diabetes mellitus patients who took metformin and acarbose alone or in combination therapy were more likely to survive hospitalization from COVID-19.[5]

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 blood concentrations.

Acarbose may produce weight loss by increasing glucagon-like peptide-1.[6] Lazzaroni E. et al. conducted a systematic analysis of the literature on non-insulin lowering drugs for weight loss in patients with type 2 diabetes mellitus.[7] Acarbose lowered weight by less than 3.2%, canagliflozin lowered weight between 3.2 to 5%, and tirzepatide lowered weight by greater than 5%.

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).

Metabolized

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

Excretion

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

Gupta S. et al. conducted a three-month study in mice to evaluate the anti-aging effects of acarbose.[8] 20-month-old C57BL/6 male and female mice were given a standard diet or a diet with 1000 ppm of acarbose. The acarbose-treated mice had decreased age-related lesions of the heart and kidney. Acarbose’s anti-aging and anti-inflammatory effects appear to be mediated thru the ERK1/2 signaling and the p38-MAPK pathways.[9]

An in vitro study suggests that acarbose could help in treating ischemic stroke by decreasing mitochondrial and lysosomal dysfunction and changing gene expression related to improving cellular survival.[10]

Yang Q. et al. conducted research on the treatment of polycystic ovarian syndrome with impaired glucose tolerance using acarbose and diet. This treatment helped improve the ovulation and pregnancy rate of the patients.[11]

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.
• 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 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 three-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 the combination of 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 GI adverse effects. 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 usually are asymptomatic and reversible once stopping drug therapy.

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 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. 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 concentrations and glycosylated hemoglobin require monitoring to assess efficacy. Serum transaminase concentrations should be checked every three 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.) as acarbose will prevent the breakdown of sucrose (table sugar) and delay glucose absorption; therefore, 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 useful, 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. [Level 5]