Mechanism of Action of Acarbose in Type 2 Diabetes Mellitus
Acarbose works by competitively and reversibly inhibiting pancreatic alpha-amylase and intestinal alpha-glucosidase enzymes, which delays carbohydrate digestion and absorption in the small intestine, thereby reducing postprandial glucose excursions. 1
Primary Mechanism
- Acarbose inhibits pancreatic alpha-amylase that normally breaks down complex starches into oligosaccharides in the small intestine lumen 1
- It also inhibits membrane-bound intestinal alpha-glucosidase enzymes that convert oligosaccharides, trisaccharides, and disaccharides to glucose and other monosaccharides in the brush border of the small intestine 1
- This enzyme inhibition results in delayed glucose absorption and reduced postprandial hyperglycemia in diabetic patients 1
- Unlike sulfonylureas, acarbose does not enhance insulin secretion, making its mechanism of action complementary to other antidiabetic medications 1
Clinical Effects
- Acarbose specifically targets postprandial glucose excursions, reducing them by approximately 16-28% after carbohydrate-rich meals 2, 3
- It lowers HbA1c by 0.5-1.2% in patients with type 2 diabetes, with greater reductions seen when baseline HbA1c is higher 4, 5
- The medication acts locally within the gastrointestinal tract, with less than 2% absorbed as active drug, which contributes to its safety profile 1
- Acarbose diminishes postprandial insulin responses by approximately 9.2%, which may help reduce hyperinsulinemia 2
Metabolic Effects
- The drug is metabolized exclusively within the gastrointestinal tract, primarily by intestinal bacteria and digestive enzymes 1
- Approximately 34% of these metabolites are absorbed and subsequently excreted in the urine 1
- One metabolite (formed by cleavage of a glucose molecule from acarbose) also has alpha-glucosidase inhibitory activity 1
- Acarbose reduces blood glucose fluctuations throughout the day, particularly after meals, which may protect beta-cell function 3
Cardiovascular Benefits
- Beyond glycemic control, acarbose has demonstrated cardiovascular benefits in clinical studies 4
- In the STOP-NIDDM trial, acarbose significantly reduced cardiovascular events in patients with impaired glucose tolerance 6
- A meta-analysis showed acarbose intake was associated with a 35% reduction in cardiovascular events in patients with type 2 diabetes 4
- Acarbose reduces postprandial triglyceride levels, which may contribute to its cardiovascular benefits 5
Clinical Applications
- Acarbose can be used as monotherapy or in combination with other antidiabetic medications including sulfonylureas, metformin, and insulin 6, 5
- It is particularly effective in patients with early diabetes and those with postprandial hyperglycemia despite normal fasting glucose 7
- In patients with dumping syndrome, acarbose effectively reduces postprandial hypoglycemia by slowing carbohydrate digestion 6
- For type 2 diabetes, acarbose is typically started at a low dose (25-50mg) with meals and gradually increased to minimize gastrointestinal side effects 6
Important Considerations and Side Effects
- The most common side effects are gastrointestinal, including flatulence, bloating, and diarrhea, occurring in approximately 30-60% of patients 8
- These side effects tend to decrease over time and can be minimized by starting with low doses and gradually titrating upward 8
- When hypoglycemia occurs in patients taking acarbose in combination with insulin or insulin secretagogues, it must be treated with glucose (not sucrose) since acarbose will inhibit the breakdown of complex carbohydrates 6
- Acarbose is contraindicated in patients with inflammatory bowel disease, colonic ulceration, intestinal obstruction, or predisposition to intestinal obstruction 8