Alpha-Glucosidase Inhibitors

Introduction

Acarbose (Precose) and miglitol (Glyset) are alpha-glucosidase inhibitors that slow the breakdown of complex carbohydrates (disaccharides and polysaccharides) into monosaccharides or glucose. The enzymatic generation and subsequent absorption of glucose is delayed and the postprandial blood glucose values, which are characteristically high in patients with type 2 diabetes (T2D), are reduced with these agents. The postprandial glucose (PPG) level is often overlooked but can significantly contribute to prolonged hyperglycemia. Acarbose and miglitol are excellent pharmacologic agents to “spread the calories” and have been shown to smooth out daytime glycemia.

Acarbose (Precose)

Acarbose has been shown to reduce the mean PPG value by approximately 50 mg/dL and the fasting glucose by 10 to 20 mg/dL. Acarbose also lowers the postprandial integrated insulin levels, as less glucose is being presented to the pancreas at any one time. Acarbose does not stimulate insulin release and does not cause hypoglycemia when used alone. The average reduction in glycosylated hemoglobin (A1C) is usually 0.5% to 1.0%. The reduction in glycemia is related to the carbohydrate content of the diet. Generally, the greater the complex carbohydrate content of the diet, the larger the reduction in postprandial hyperglycemia. In addition, a large-scale trial has demonstrated that when acarbose is given to patients with newly diagnosed diabetes (duration of up to 1 year) with poor metabolic control (baseline A1C >10%), a 3.0% to 4.6% reduction in A1C can be seen. Since acarbose primarily reduces the PPG and does not cause hypoglycemia, the drop in A1C is usually not as dramatic as one would see with the sulfonylurea (SFUs), which can cause hypoglycemia (the A1C is an average of the highs and lows of plasma glucose).

The combined use of acarbose with metformin (MET) and/or insulin has been approved by the Food and Drug Administration (FDA). Acarbose has been used successfully with thiazolidinediones (TZDs) and repaglinide for the treatment of T2D, although the latter two combinations are not yet approved by the FDA.

Side Effects of Acarbose

The main side effect of acarbose is flatulence. Soft stools or diarrhea and mild abdominal pain have also been reported. Many of the symptoms are dose-related and transient, occurring with the highest frequency during the first 8 weeks of therapy. The symptoms are probably caused by the osmotic effect of undigested carbohydrates in the distal bowel. The most important factor in avoiding side effects is to titrate acarbose slowly. Because acarbose is not absorbed systemically to any significant degree and does not cause hypoglycemia, it has been suggested that it may be safer than some of the other oral agents in patients with kidney disease, in the elderly and in children with T2D.

Prescribing Acarbose

The recommended maintenance dosage of acarbose is 50 mg to 100 mg orally 3 times a day with meals. The suggested starting dose of acarbose is 25 mg/day, which should be titrated up slowly to the maintenance dosage of 50 mg to 100 mg tid to avoid side effects (Table 13-1).

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Miglitol (Glyset)

Miglitol is a similar compound to acarbose that also has alpha-glucosidase inhibitor (AGI) activity in the gut, thereby delaying or preventing the digestion and absorption of complex carbohydrates. In a similar fashion to acarbose, miglitol does not directly stimulate insulin secretion and does not cause hypoglycemia when used alone. The main clinical effect of miglitol is to lower the PPG value with additive effects of lowering postprandial insulin levels and a lesser reduction in the fasting plasma glucose (FPG) values. The magnitude of reductions of the A1C values is on the same order of magnitude as seen with acarbose, although miglitol 50 mg tid has been shown to be equivalent to acarbose 100 mg tid in terms of efficacy. Miglitol can be safely added to all other oral agents on the market as well as combined with insulin.

Sides Effects of Miglitol

Flatulence is the main gastrointestinal (GI) side effect experienced with miglitol therapy, although it may be better tolerated than other carbohydrate-absorption inhibitors.

Prescribing Miglitol

The recommended maintenance dosage of miglitol is 25 mg to 50 mg orally three times a day with meals. The suggested starting dose of miglitol is 25 mg/day, which should be titrated up slowly to the maintenance dosage of 25 mg to 50 mg tid to avoid side effects (Table 13-1).