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Alpha Glucosidase Inhibitors

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Last Update: August 12, 2022.

Continuing Education Activity

Alpha-glucosidase inhibitors (AGIs) are a group of antidiabetic drugs used for the management of type 2 diabetes mellitus. This activity outlines the indications, mechanism of action, contraindications, adverse effects, monitoring, and other key elements required by healthcare professionals involved in the management of type 2 diabetes mellitus and its complications.

Objectives:

  • Identify the mechanism of action and administration of alpha-glucosidase inhibitors.
  • Describe the adverse effects and contraindications of alpha-glucosidase inhibitors.
  • Review the appropriate monitoring and toxicity of alpha-glucosidase inhibitors.
  • Summarize interprofessional team strategies for improving care coordination and communication to optimize the use of alpha-glucosidase inhibitors and improve outcomes.
Access free multiple choice questions on this topic.

Indications

Alpha-glucosidase inhibitors (AGIs) are a class of drugs that are used in the treatment of type 2 diabetes mellitus alone or combined with other antidiabetic drugs. They may also be used in patients with impaired glucose tolerance and delay the occurrence of type 2 diabetes mellitus in these patients. They are particularly useful for patients who are at risk of hypoglycemia or lactic acidosis and, thus, are not suitable candidates for other antidiabetic drugs such as sulfonylureas and metformin.[1][2][3][4]                      

The FDA approves AGIs for the treatment of type 2 diabetes mellitus. They have shown some benefits in type 1 diabetes mellitus and gestational diabetes mellitus but are not FDA-approved for these indications. Acarbose has been shown to decrease body weight in a worldwide observational study.[5]

AGIs are particularly useful for reducing postprandial hyperglycemia. They modestly decrease glycosylated hemoglobin levels and also reduce postprandial insulin concentration. Compared with oral antihyperglycemic drugs, they also reduce glucose variability throughout the day. They, however, do not affect fasting insulin and serum triglyceride concentrations. Controlling postprandial hyperglycemia is essential as it correlates with the development of microvascular complications and increases the risk for the development of cardiovascular diseases. This link between postprandial blood glucose (PPG) and long-term diabetic complications is even stronger than that of fasting hyperglycemia.[6][7]

Acarbose has been shown to increase life expectancy in patients with type 2 diabetes mellitus and reduces the risk of the development of cardiovascular events in patients with impaired glucose tolerance. It has proven efficacy in stabilizing carotid plaques; by reducing hyperglycemia, it counters oxidative stress and endothelial dysfunction.[8][9]

Mechanism of Action

Alpha-glucosidase inhibitors inhibit the absorption of carbohydrates from the small intestine. They competitively inhibit enzymes that convert complex non-absorbable carbohydrates into simple absorbable carbohydrates. These enzymes include glucoamylase, sucrase, maltase, and isomaltase. By delaying carbohydrate absorption, they reduce the rise in postprandial blood glucose concentrations by about 3 mmol/l. 

Acarbose is the most commonly used drug in this class and also the most widely studied one. Others include voglibose and miglitol. Acarbose inhibits alpha-amylase, maltase, sucrase, and dextranase and is most effective against glucoamylase. It does not affect lactase, which is a beta-glucosidase. Acarbose and voglibose (not FDA-approved in the USA) are poorly absorbed from the gut, have low bioavailability, and are excreted in the stool. Miglitol, on the other hand, is absorbed from the gut completely and is excreted through the renal route. Acarbose undergoes metabolism in the colon, while miglitol and voglibose have no metabolites.[1][10][3]

Administration

Alpha-glucosidase inhibitors are administered orally. They should be taken three times a day with the first bite of each meal. The general recommendation is to always start with a lower dose, both to reduce the frequency of adverse effects and to achieve the desired dose for optimal glycemic control. Acarbose should be started at a dose of 25 mg three times daily, titrating thereafter every 4 to 8 weeks, with the maximum dose being 100 mg three times a day. For voglibose, the recommended initial dose is 0.2 mg three times daily, which can be increased up to 0.3 mg three times daily. For miglitol, the initial dose is 25 mg three times daily, and the maximum dose is 100 mg thrice a day.[1]

The safety of AGIs has not been established in pediatric and pregnant patients, warranting caution if their use is indicated in these populations.

The effectiveness of AGIs is affected by the number of complex carbohydrates in the diet. A carbohydrate-rich diet also increases the severity of gastrointestinal side effects.[11]

Adverse Effects

Gastrointestinal disturbances are the most commonly reported side effects of alpha-glucosidase inhibitors. These result from the degradation of undigested carbohydrates by bacteria in the colon, which causes excessive gas formation. Flatulence is the most commonly reported side effect, appearing in about 78% of the cases. Diarrhea and abdominal pain may also occur. The use of acarbose (but not other AGIs) has potential links with hepatitis in some instances. These abate with time, and their severity can be further reduced by starting with a low dose. A carbohydrate-rich diet can precipitate these adverse effects.[1][12]

Contraindications

Alpha-glucosidase inhibitors are contraindicated in any of the conditions that can worsen due to excess gas formation in the gut. It is also contraindicated in patients who are either suffering from intestinal obstruction or are at risk of intestinal obstruction. Other contraindications include diabetic ketoacidosis, chronic intestinal disease, colonic ulceration, inflammatory bowel disease, and known hypersensitivity to this group of drugs.[1]

Monitoring

There are reports of cases of acute hepatitis with the use of acarbose; hence, liver function tests (LFTs) require monitoring before and during treatment. If the concentrations of LFTs become abnormal during treatment, the clinician should reduce the dose or discontinue therapy. The monitoring of efficacy involves checking glycosylated hemoglobin (Hb1Ac) and 1- or 2-hour postprandial plasma glucose concentrations.[1]

Toxicity

Unlike sulfonylureas, this group of drugs does not cause hypoglycemia. However, combination therapy with sulfonylureas or insulin poses the risk of hypoglycemia; in that case, the patient should understand the need to keep glucose with them. Disaccharides such as sucrose and polysaccharides would not be suitable for reversing hypoglycemia in patients taking AGIs as the effects of the drug would impair their digestion and absorption.[13]

Enhancing Healthcare Team Outcomes

Alpha-glucosidase inhibitors are effective in patients with type 2 diabetes mellitus in improving the metabolic profile and potentially reducing the risk of long-term complications of hyperglycemia. They may be used as monotherapy or in combination with other antihyperglycemic drugs and insulin. They do not have correlations with any serious adverse effects. This makes them particularly useful for patients who have renal, cardiorespiratory, or liver problems, who are at a higher risk for developing lactic acidosis and, therefore, are not good candidates for metformin therapy. They also do not cause hypoglycemia, making them a useful substitute for sulfonylureas, which are associated with frequent occurrences of hypoglycemia. Patients should receive counsel to maintain an appropriate diet as high levels of carbohydrates can worsen gastrointestinal side effects. If used in combination with other antidiabetic drugs, the patient should carry glucose with them for the quick reversal of hypoglycemia. Management of type 2 diabetes mellitus requires an interdisciplinary approach; the primary care provider, the pharmacist, and the nurse practitioner should educate the patients regarding side effects and instruct them to maintain an appropriately healthy diet.[14][15] [Level 1]

Review Questions

References

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2.
Zhang M, Feng R, Yang M, Qian C, Wang Z, Liu W, Ma J. Effects of metformin, acarbose, and sitagliptin monotherapy on gut microbiota in Zucker diabetic fatty rats. BMJ Open Diabetes Res Care. 2019;7(1):e000717. [PMC free article: PMC6777410] [PubMed: 31641523]
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Kumar S, Narwal S, Kumar V, Prakash O. α-glucosidase inhibitors from plants: A natural approach to treat diabetes. Pharmacogn Rev. 2011 Jan;5(9):19-29. [PMC free article: PMC3210010] [PubMed: 22096315]
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Min SH, Yoon JH, Hahn S, Cho YM. Efficacy and safety of combination therapy with an α-glucosidase inhibitor and a dipeptidyl peptidase-4 inhibitor in patients with type 2 diabetes mellitus: A systematic review with meta-analysis. J Diabetes Investig. 2018 Jul;9(4):893-902. [PMC free article: PMC6031526] [PubMed: 28950431]
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Gao X, Cai X, Yang W, Chen Y, Han X, Ji L. Meta-analysis and critical review on the efficacy and safety of alpha-glucosidase inhibitors in Asian and non-Asian populations. J Diabetes Investig. 2018 Mar;9(2):321-331. [PMC free article: PMC5835463] [PubMed: 28685995]
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Kim MK, Suk JH, Kwon MJ, Chung HS, Yoon CS, Jun HJ, Ko JH, Kim TK, Lee SH, Oh MK, Rhee BD, Park JH. Nateglinide and acarbose for postprandial glucose control after optimizing fasting glucose with insulin glargine in patients with type 2 diabetes. Diabetes Res Clin Pract. 2011 Jun;92(3):322-8. [PubMed: 21376417]
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Yang HK, Lee SH, Shin J, Choi YH, Ahn YB, Lee BW, Rhee EJ, Min KW, Yoon KH. Acarbose Add-on Therapy in Patients with Type 2 Diabetes Mellitus with Metformin and Sitagliptin Failure: A Multicenter, Randomized, Double-Blind, Placebo-Controlled Study. Diabetes Metab J. 2019 Jun;43(3):287-301. [PMC free article: PMC6581543] [PubMed: 30604599]
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DiNicolantonio JJ, Bhutani J, O'Keefe JH. Acarbose: safe and effective for lowering postprandial hyperglycaemia and improving cardiovascular outcomes. Open Heart. 2015;2(1):e000327. [PMC free article: PMC4620230] [PubMed: 26512331]
10.
Göke B, Fuder H, Wieckhorst G, Theiss U, Stridde E, Littke T, Kleist P, Arnold R, Lücker PW. Voglibose (AO-128) is an efficient alpha-glucosidase inhibitor and mobilizes the endogenous GLP-1 reserve. Digestion. 1995;56(6):493-501. [PubMed: 8536820]
11.
Kalra S. Alpha glucosidase inhibitors. J Pak Med Assoc. 2014 Apr;64(4):474-6. [PubMed: 24864650]
12.
Reuser AJ, Wisselaar HA. An evaluation of the potential side-effects of alpha-glucosidase inhibitors used for the management of diabetes mellitus. Eur J Clin Invest. 1994 Aug;24 Suppl 3:19-24. [PubMed: 8001622]
13.
Hedrington MS, Davis SN. Considerations when using alpha-glucosidase inhibitors in the treatment of type 2 diabetes. Expert Opin Pharmacother. 2019 Dec;20(18):2229-2235. [PubMed: 31593486]
14.
Dash RP, Babu RJ, Srinivas NR. Reappraisal and perspectives of clinical drug-drug interaction potential of α-glucosidase inhibitors such as acarbose, voglibose and miglitol in the treatment of type 2 diabetes mellitus. Xenobiotica. 2018 Jan;48(1):89-108. [PubMed: 28010166]
15.
Cai X, Han X, Luo Y, Ji L. Comparisons of the efficacy of alpha glucosidase inhibitors on type 2 diabetes patients between Asian and Caucasian. PLoS One. 2013;8(11):e79421. [PMC free article: PMC3827349] [PubMed: 24236131]
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Bookshelf ID: NBK557848PMID: 32496728

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