Cochrane for Clinicians
Putting Evidence into Practice
Are Alpha-glucosidase Inhibitors Effective for Control of Type 2 Diabetes?
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Am Fam Physician. 2006 Feb 1;73(3):433-434.
This clinical content conforms to AAFP criteria for evidence-based continuing medical education (EB CME). EB CME is clinical content presented with practice recommendations supported by evidence that has been reviewed systematically by an AAFP-approved source. The practice recommendations in this activity are available online at http://www.cochrane.org/cochrane/revabstr/AB003639.htm.
A 55-year-old man with diabetes has used diet to control his glucose levels for the past six years. His A1C level gradually has risen to 7.5 percent, and he wants to discuss options for medical therapy.
Is monotherapy with alpha-glucosidase inhibitors effective in reducing complications and improving glucose control in patients with diabetes?
The use of alpha-glucosidase inhibitors has a modest effect on intermediate diabetes-control endpoints such as postprandial blood glucose, postprandial insulin levels, and A1C levels. There is no evidence, however, of improvement in mortality, morbidity, or quality of life. In comparisons with sulfonylureas, alpha-glucosidase inhibitors had less effect on intermediate diabetes-control endpoints and had a greater incidence of adverse effects. The use of alpha-glucosidase inhibitors had no effect on plasma lipid levels or body weight.1
Guidelines allow patients and physicians to choose from several classes of agents and combinations of agents as initial therapy for type 2 diabetes. Most authorities suggest biguanides (of which metformin [Glucophage] is the only available agent) for patients who are overweight and have no contraindication to that class, but no consensus has been reached on any other specific guidance.2
Alpha-glucosidase inhibitors are considered to be less potent than the other classes of medications that are used for type 2 diabetes; however, alpha-glucosidase inhibitors have fewer potential metabolic side effects.3 They inhibit the absorption of complex carbohydrates and are particularly useful for controlling postprandial glucose elevations, with little effect on fasting glucose levels.
In this Cochrane meta-analysis,1 alpha-glucosidase inhibitors were found to reduce glycated hemoglobin by 0.8 percent when compared with placebo (95% confidence interval, −0.9 to −0.6; 28 comparisons). Alpha-glucosidase inhibitors have been shown to have a very low incidence of hypoglycemia, particularly in comparison with sulfonylureas and insulin.
Long-term compliance with alpha-glucosidase inhibitors is low because of gastrointestinal side effects including flatulence and diarrhea. One study4 found that only 31 percent of patients were still taking the medication after three years.
Patients for whom an alpha-glucosidase inhibitor might be appropriate as initial monotherapy include those who have liver or kidney disease that may be a contraindication to other medications and those at high risk of hypoglycemia. It might also be appropriate for those who would prefer to avoid systemic medications. Alpha-glucosidase inhibitor monotherapy would not be appropriate for patients who have very high A1C levels or for those who have difficulty with medication compliance.
This review1 points out that there is little evidence for mortality reduction, cardiovascular morbidity reduction, or improvement in quality of life with any of the available therapies for type 2 diabetes. Some reduction in cardiovascular morbidity was found among obese patients who received metformin in the U.K. Prospective Diabetes Study.5 As a result of this finding, the International Diabetes Federation has issued a guideline stating that metformin should be the initial drug of choice for all adult patients who have no evidence of renal impairment.2
Background. Alpha-glucosidase inhibitors such as acarbose (Precose) or miglitol (Glyset) have the potential to improve glycemic control in type 2 diabetes. The true value of these agents, especially in regard to diabetes-related mortality and morbidity, has never been investigated in a systematic literature review and meta-analysis.
Objectives. To assess the effects of alpha-glucosidase inhibitors in patients with type 2 diabetes.
Search Strategy. The reviewers1 searched The Cochrane Library, MEDLINE, EMBASE, Current Contents, LILACS, databases of ongoing trials, and reference lists of reviews on the topic of alpha-glucosidase inhibitors. They also contacted experts and manufacturers for additional trials. Date of most recent search: December 2003 (Current Contents) and April 2003 (other databases).
Selection Criteria. Randomized controlled trials of at least 12 weeks’ duration that compared alpha-glucosidase inhibitor monotherapy in patients with type 2 diabetes with any other intervention and that included at least one of the following outcomes: mortality, morbidity, quality of life, glycemic control, lipids, insulin levels, body weight, adverse events.
Data Collection and Analysis. Two reviewers read all abstracts, assessed quality, and extracted data independently. Discrepancies were resolved by consensus or by the judgment of a third reviewer. A statistician checked all extracted data entrance in the database. The reviewers attempted to contact all authors for data clarification.
Primary Results. The review included 41 trials (8,130 participants); 30 investigated acarbose, seven miglitol, and one voglibose [not available in the United States], and three trials compared alpha-glucosidase inhibitors. Study duration was 24 weeks in most cases and only two studies lasted amply longer than one year. The reviewers found few data on mortality, morbidity, and quality of life. Acarbose had a clear effect on glycemic control compared with placebo: glycated hemoglobin −0.8 percent (95% confidence interval [CI], −0.9 to −0.7), fasting blood glucose −1.1 mmol per L (95% CI, −1.4 to −0.9), postload blood glucose −2.3 mmol per L (95% CI, −2.7 to −1.9). The effect on glycated hemoglobin by acarbose was not dose dependent. The reviewers found a decreasing effect on postload insulin and no clinically relevant effects on lipids or body weight. Adverse effects were mostly of gastrointestinal origin and dose dependent. Compared with sulfonylurea, acarbose decreased fasting and postload insulin levels by −24.8 pmol per L (95% CI, −43.3 to −6.3) and −133.2 pmol per L (95% CI, −184.5 to −81.8), respectively, and acarbose caused more adverse effects.
Reviewers’ Conclusions. It remains unclear whether alpha-glucosidase inhibitors influence mortality or morbidity in patients with type 2 diabetes. Alpha-glucosidase inhibitors have a significant effect on glycemic control and insulin levels, but no statistically significant effect on lipids and body weight. These effects are less sure when alpha-glucosidase inhibitors are used for a longer duration. Acarbose dosages higher than 50 mg three times daily offer no additional effect on glycated hemoglobin and cause more adverse effects. Compared with sulfonylurea, alpha-glucosidase inhibitors lower fasting and postload insulin levels and have an inferior profile regarding glycemic control and adverse effects.
These summaries have been derived from Cochrane reviews published in the Cochrane Database of SystematicReviews in the Cochrane Library. Their content has, as far as possible, been checked with the authors of the originalreviews, but the summaries should not be regarded as an official product of the Cochrane Collaboration; minorediting changes have been made to the text (http://www.cochrane.org).
DAN BREWER, M.D., is associate professor in the Department of Family Medicine at the University of Tennessee, Knoxville.
Address correspondence to Dan Brewer, M.D., Department of Family Medicine, University of Tennessee, 1924 Alcoa Highway, Knoxville, TN 37920 (e-mail: firstname.lastname@example.org). Reprints are not available from the author.
1. Van de Laar FA, Lucassen PL, Akkermans RP, Van de Lisdonk EH, Rutten GE, Van Weel C. Alphaglucosidase inhibitors for type 2 diabetes mellitus. Cochrane Database Syst Rev. 2005;(2):CD003639.
2. IDF Clinical Guidelines Task Force. Global guideline for type 2 diabetes. Brussels: International Diabetes Federation, 2005.
3. Inzucchi SE. Oral antihyperglycemic therapy for type 2 diabetes: scientific review. JAMA. 2002;287:360–72.
4. Holman RR, Cull CA, Turner RC. A randomized double-blind trial of acarbose in type 2 diabetes shows improved glycemic control over 3 years (U.K. Prospective Diabetes Study 44) [published correction appears in Diabetes Care 1999;22:1922]. Diabetes Care. 1999;22:960–4.
5. U. K. Prospective Diabetes Study Group. Effect of intensive blood-glucose control with metformin on complications in overweight patients with type 2 diabetes (U.K. Prospective Diabetes Study 34) [published correction appears in Lancet 1998;352:1557]. Lancet. 1998;352:854–65.
The Cochrane Abstract is a summary of a review from the Cochrane Library. It is accompanied by an interpretation that will help clinicians put evidence into practice. Dan Brewer, M.D., presents a clinical scenario and question based on the Cochrane Abstract, followed by an evidence-based answer and a full critique of the review.
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