Alpha-glucosidase inhibitors are oral anti-diabetic drugs used for diabetes mellitus type 2 that work by preventing the digestion of carbohydrates (such as starch and table sugar). Carbohydrates are normally converted into simple sugars (monosaccharides), which can be absorbed through the intestine. Hence, alpha-glucosidase inhibitors reduce the impact of carbohydrates on blood sugar.
Examples and differences
Examples of alpha-glucosidase inhibitors include:
Even though the drugs have a similar mechanism of action, there are subtle differences between acarbose and miglitol. Acarbose is an oligosaccharide, whereas miglitol resembles a monosaccharide. Miglitol is fairly well absorbed by the body, as opposed to acarbose. Moreover, acarbose inhibits pancreatic alpha-amylase in addition to alpha-glucosidase.
Natural alpha glucosidase inhibitors
For example, research has shown the culinary mushroom Maitake (Grifola frondosa) has a hypoglycemic effect. The reason Maitake lowers blood sugar is because the mushroom naturally contains an alpha glucosidase inhibitor. Another plant attracting a lot of attention is Salacia oblonga.
Role in clinical use
Alpha-glucosidase inhibitors are used to establish greater glycemic control over hyperglycemia in diabetes mellitus type 2, particularly with regard to postprandial hyperglycemia. They may be used as monotherapy in conjunction with an appropriate diabetic diet and exercise, or they may be used in conjunction with other anti-diabetic drugs.
Mechanism of action
Alpha-glucosidase inhibitors are saccharides that act as competitive inhibitors of enzymes needed to digest carbohydrates: specifically alpha-glucosidase enzymes in the brush border of the small intestines. The membrane-bound intestinal alpha-glucosidases hydrolyze oligosaccharides, trisaccharides, and disaccharides to glucose and other monosaccharides in the small intestine.
Acarbose also blocks pancreatic alpha-amylase in addition to inhibiting membrane-bound alpha-glucosidases. Pancreatic alpha-amylase hydrolyzes complex starches to oligosaccharides in the lumen of the small intestine.
Inhibition of these enzyme systems reduces the rate of digestion of carbohydrates. Less glucose is absorbed because the carbohydrates are not broken down into glucose molecules. In diabetic patients, the short-term effect of these drugs therapies is to decrease current blood glucose levels: the long term effect is a small reduction in hemoglobin A1c level.
Since alpha-glucosidase inhibitors are competitive inhibitors of the digestive enzymes, they must be taken at the start of main meals to have maximal effect. Their effects on blood sugar levels following meals will depend on the amount of complex carbohydrates in the meal.
Side effects & precautions
Since alpha-glucosidase inhibitors prevent the degradation of complex carbohydrates into glucose, the carbohydrates will remain in the intestine. In the colon, bacteria will digest the complex carbohydrates, thereby causing gastrointestinal side effects such as flatulence and diarrhea. Since these effects are dose-related, it is generally advised to start with a low dose and gradually increase the dose to the desired amount. Pneumatosis cystoides intestinalis is another reported side effect. If a patient using an alpha-glucosidase inhibitor suffers from an episode of hypoglycemia, the patient should eat something containing monosaccharides, such as glucose tablets. Since the drug will prevent the digestion of polysaccharides (or non-monosaccharides), non-monosaccharide foods may not effectively reverse a hypoglycemic episode in a patient taking an alpha-glucosidase inhibitor.
- Benalla W. Bellahcen S. Bnouham M. Current Diabetes Reviews. "Antidiabetic medicinal plants as a source of alpha glucosidase inhibitors. [Review]" Current Diabetes Reviews. 6(4):247-54, 2010 Jul 1.
- Ji F. Xiao G. Dong L. Ma Z. Ni J. Zhongguo Zhong Yao Za Zhi/Zhongguo Zhongyao Zazhi "Development of alpha-glucosidase inhibitor from medicinal herbs. [Review]" (mostly in Chinese) China Journal of Chinese Materia Medica. 35(12):1633-40, 2010 Jun.
- name="pmid11903406" Konno S, Tortorelis DG, Fullerton SA, Samadi AA, Hettiarachchi J, Tazaki H. (Dec 2001), "A possible hypoglycaemic effect of maitake mushroom on Type 2 diabetic patients.", Diabet Med. 18 (12): 1010, doi:10.1046/j.1464-5491.2001.00532-5.x, ISSN 0742-3071, PMID 11903406
- Hong L, Xun M, Wutong W. (Apr 2007), "Anti-diabetic effect of an alpha-glucan from fruit body of maitake (Grifola frondosa) on KK-Ay mice.", J Pharm Pharmacol 59 (4): 575–82, doi:10.1211/jpp.59.4.0013, ISSN 0022-3573, PMID 17430642
- Kubo K, Aoki H, Nanba H. (Aug 1994), "Anti-diabetic activity present in the fruit body of Grifola frondosa (Maitake). I.", Biol Pharm Bull. 17 (8): 1106–10, doi:10.1248/bpb.17.1106, ISSN 0918-6158, PMID 7820117
- Lo HC, Hsu TH, Chen CY. (2008), "Submerged culture mycelium and broth of Grifola frondosa improve glycemic responses in diabetic rats.", Am J Chin Med. 36 (2): 265–85, doi:10.1142/S0192415X0800576X, ISSN 0192-415X, PMID 18457360
- Manohar V, Talpur NA, Echard BW, Lieberman S, Preuss HG. (Jan 2002), "Effects of a water-soluble extract of maitake mushroom on circulating glucose/insulin concentrations in KK mice.", Diabetes Obes Metab. 4 (1): 43–8, doi:10.1046/j.1463-1326.2002.00180.x, ISSN 1462-8902, PMID 11874441
- Horio H, Ohtsuru M. (Feb 2001), "Maitake (Grifola frondosa) improve glucose tolerance of experimental diabetic rats.", J Nutr Sci Vitaminol (Tokyo). 47 (1): 57–63, doi:10.3177/jnsv.47.57, ISSN 0301-4800, PMID 11349892
- Samantha J. Venable; Diane S. Aschenbrenner, Drug Therapy In Nursing, Hagerstown, MD: Lippincott Williams & Wilkins, ISBN 0-7817-4839-9