Practicalities

Efficacy, side effects, and compliance strongly depend on rational indications, education of patients on how to use the drug, and good dietary advice. Even with good clinical practice, a considerable variation in response and side effects is seen. Side effects depend, among other things, on the dose and time intervals for titration of optimal therapeutic dosage. It is essential to start with low doses of 25 mg of acarbose or miglitol twice a day, with a stepwise increase in 2 to 3 week intervals. A study in type 2 diabetes patients treated with sulfonylurea compared the tolerability of stepwise increase with an initial dose of 100 mg three times per day of acarbose (23). The stepwise increase in dosage reduced specific side effects from 70% to 31%. The maximum dosage for acarbose and miglitol is usually 100 mg three times per day. There are, however, controlled studies that show that 200 mg three times per day is more effective, but has a higher adverse event rate (48).

After 3 to 4 weeks gastrointestinal side effects diminish to < 20% in almost all studies. In long-term studies, the great majority of discontinuations because of side effects happen during the first 3 months. It is important to reinforce dietary advice before treatment and if side effects occur. A high content of raffined carbohydrates, and a diet rich in fat and protein are causes of gastrointestinal discomfort. Patients should be made aware that side effects are due to the mode of action, are mostly transient, and can be prevented by prudent diet. Table 6 summarizes some guidelines for patients to help overcome difficulties.

Patients should also take blood glucose levels twice a week at 1 to 2 h postprandial to see the benefit of treatment. With AGI treatment, fasting blood glucose levels in the first month of treatment is not indicative of therapy success.

TABLE 5 Indications for AGIs as First-Line Drug Treatment in Type 2 Diabetes

Newly diagnosed patients insufficiently treated with diet and dominating postprandial hyperglycemia Elderly multimorbid patients

Elderly patients with weight gain or hypoglycemia under treatment with insulin secretagogues Hepatic and renal dysfunction

Abbreviation: AGIs, alpha-glucosidase inhibitors.

TABLE 6 Advice to Patients to Overcome Difficulties with AGIs Start low, go slow

Prefer nutrients with complex carbohydrates (rice, pasta, full bread, vegetables, fruits) Avoid refined carbohydrates (sugar, sweets). Take only three meals per day Avoid laxatives, such as sugar alcohols (sorbitol)

Control your postprandial blood glucose to experience the efficacy of treatment In most cases gastrointestinal side effects are transient

Abbreviation: AGIs, alpha-glucosidase inhibitors.

USE OF AGIs IN PRIMARY PREVENTION OF TYPE 2 DIABETES

IGT is an accepted risk factor for both conversion to diabetes and cardiovascular disease. Prevalence of IGT in all nations with westernized lifestyles is > 15% in subjects aged > 40 years. Primary prevention efforts with lifestyle modification are therefore of high priority. In terms of medical intervention in subjects with IGT, AGIs have been shown to improve insulin sensitivity and reduce proinsulin secretion (27,28). In the STOP-NIDDM trial, a large placebo-controlled multinational study of 1429 subjects with IGT, acarbose reduced the annual incidence of diabetes by 36% in the intention to treat analysis (25). Acarbose is now registered in 26 countries as a drug for treatment of IGT. This was associated with a significantly lower event-rate of cardiovascular comorbidities. No serious adverse event associated with acarbose was observed during the 3 to 4 year follow-up.

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