Alpha-glucosidase inhibitors for patients with type 2 diabetes: results from a Cochrane systematic review and meta-analysis.

OBJECTIVE To review the effects of monotherapy with alpha-glucosidase inhibitors (AGIs) for patients with type 2 diabetes, with respect to mortality, morbidity, glycemic control, insulin levels, plasma lipids, body weight, and side effects. RESEARCH DESIGN AND METHODS We systematically searched the Cochrane Central register of Controlled Trials, MEDLINE, EMBASE, Current Contents, LILACS, databases of ongoing trials, and reference lists, and we contacted experts and manufacturers. Inclusion criteria were randomized controlled trials of at least 12 weeks' duration, AGI monotherapy compared with any intervention, and one of the following outcome measures: mortality, morbidity, GHb, blood glucose, lipids, insulin levels, body weight, or side effects. Two independent reviewers assessed all abstracts, extracted all data, and assessed quality. We contacted all authors for data clarification. Continuous data were expressed as weighted mean differences and analyzed with a random-effects model. Possible influences of study characteristics and quality were assessed in sensitivity and meta-regression analyses. RESULTS Forty-one studies were included in the review (30 acarbose, 7 miglitol, 1 voglibose, and 3 combined), and heterogeneity was limited. We found no evidence for an effect on mortality or morbidity. Compared with placebo, AGIs had a beneficial effect on GHb (acarbose -0.77%; miglitol -0.68%), fasting and postload blood glucose and postload insulin. With acarbose dosages higher than 50 mg t.i.d., the effect on GHb was the same, but the occurrence of side effects increased. Acarbose decreased the BMI by 0.17 kg/m2 (95% CI 0.08-0.26). None of the AGIs had an effect on plasma lipids. Compared with sulfonylurea, AGIs seemed inferior with respect to glycemic control, but they reduced fasting and postload insulin levels. For comparisons with other agents, little data were available. CONCLUSIONS We found no evidence for an effect on mortality or morbidity. AGIs have clear beneficial effects on glycemic control and postload insulin levels but not on plasma lipids. There is no need for dosages higher than 50 mg acarbose t.i.d.

[1]  R. Johnston Metabolic and Endocrine Disorders , 2006 .

[2]  P. Lucassen,et al.  No evidence for a reduction of myocardial infarctions by acarbose. , 2004, European heart journal.

[3]  J. Buse,et al.  The effects of oral anti‐hyperglycaemic medications on serum lipid profiles in patients with type 2 diabetes , 2004, Diabetes, obesity & metabolism.

[4]  M. Hanefeld,et al.  Acarbose reduces the risk for myocardial infarction in type 2 diabetic patients: meta-analysis of seven long-term studies. , 2004, European heart journal.

[5]  C. van Weel,et al.  Is acarbose equivalent to tolbutamide as first treatment for newly diagnosed type 2 diabetes in general practice? A randomised controlled trial. , 2004, Diabetes research and clinical practice.

[6]  B. Clarke,et al.  Effectiveness of acarbose, an alpha-glucosidase inhibitor, in uncontrolled non-obese non-insulin dependent diabetes , 2004, European Journal of Clinical Pharmacology.

[7]  H. Breuer Review of acarbose therapeutic strategies in the long-term treatment and in the prevention of type 2 diabetes. , 2003, International journal of clinical pharmacology and therapeutics.

[8]  B. Djulbegovic,et al.  Pharmaceutical industry sponsorship and research outcome and quality: systematic review , 2003, BMJ : British Medical Journal.

[9]  T. Wascher,et al.  Long-Term Improvement of Metabolic Control by Acarbose in Type 2 Diabetes Patients Poorly Controlled with Maximum Sulfonylurea Therapy , 2003, Clinical drug investigation.

[10]  J. Rosenthal,et al.  Effects on Blood Pressure of the α-Glucosidase Inhibitor Acarbose Compared with the Insulin Enhancer Glibenclamide in Patients with Hypertension and Type 2 Diabetes Mellitus , 2002 .

[11]  M. Zanella,et al.  Improved glycemic control by acarbose therapy in hypertensive diabetic patients: effects on blood pressure and hormonal parameters. , 2002, Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologicas.

[12]  T. Walter,et al.  The effect of combination treatment with acarbose and glibenclamide on postprandial glucose and insulin profiles: additive blood glucose lowering effect and decreased hypoglycaemia. , 2002, Diabetes, nutrition & metabolism.

[13]  A. Golay,et al.  Acarbose improves indirectly both insulin resistance and secretion in obese type 2 diabetic patients. , 2002, Diabetes & metabolism.

[14]  M. Drent,et al.  Dose-dependent efficacy of miglitol, an alpha-glucosidase inhibitor, in type 2 diabetic patients on diet alone: results of a 24-week double-blind placebo-controlled study. , 2002, Diabetes, nutrition & metabolism.

[15]  K. Takami,et al.  Effects of dietary treatment alone or diet with voglibose or glyburide on abdominal adipose tissue and metabolic abnormalities in patients with newly diagnosed type 2 diabetes. , 2002, Diabetes care.

[16]  P. Home,et al.  Clinical guidelines and evidence review for Type 2 diabetes: management of blood glucose , 2002 .

[17]  H. Laube Acarbose: An update of its therapeutic use in diabetes treatment , 2002 .

[18]  Douglas G. Altman,et al.  Systematic Reviews in Health Care: Meta-Analysis in Context: Second Edition , 2008 .

[19]  H. Fujita,et al.  Long-term ingestion of a fermented soybean-derived Touchi-extract with alpha-glucosidase inhibitory activity is safe and effective in humans with borderline and mild type-2 diabetes. , 2001, The Journal of nutrition.

[20]  J. Chiasson,et al.  The synergistic effect of miglitol plus metformin combination therapy in the treatment of type 2 diabetes. , 2001, Diabetes care.

[21]  R. Campbell,et al.  Miglitol: Assessment of its Role in the Treatment of Patients with Diabetes Mellitus , 2000, The Annals of pharmacotherapy.

[22]  D. Lau,et al.  Effect of acarbose on insulin sensitivity in elderly patients with diabetes. , 2000, Diabetes care.

[23]  C. Spencer,et al.  Miglitol , 2000, Drugs.

[24]  K. Karșıdağ,et al.  Comparison of acarbose and gliclazide as first-line agents in patients with type 2 diabetes. , 2000 .

[25]  D. Heim,et al.  Effects of acarbose treatment in Type 2 diabetic patients under dietary training: a multicentre, double-blind, placebo-controlled, 2-year study. , 1999, Diabetes, nutrition & metabolism.

[26]  T. Welborn,et al.  Will acarbose improve the metabolic abnormalities of insulin-resistant type 2 diabetes mellitus? , 1999, Diabetes research and clinical practice.

[27]  R. Torella,et al.  [Non-insulin-dependent diabetes mellitus associated with nonalcoholic liver cirrhosis: an evaluation of treatment with the intestinal alpha-glucosidase inhibitor acarbose]. , 1999, Annali italiani di medicina interna : organo ufficiale della Societa italiana di medicina interna.

[28]  J. Chan,et al.  An Asian Multicenter Clinical Trial to Assess the Efficacy and Tolerability of Acarbose Compared With Placebo in Type 2 Diabetic Patients Previously Treated With Diet , 1998, Diabetes Care.

[29]  P. Raskin,et al.  Advantages of α-glucosidase inhibition as monotherapy in elderly type 2 diabetic patients , 1998 .

[30]  M. Hanefeld,et al.  European study on dose-response relationship of acarbose as a first-line drug in non-insulin-dependent diabetes mellitus: efficacy and safety of low and high doses , 1998, Acta Diabetologica.

[31]  D. Kelley,et al.  Chronic Treatment of African-American Type 2 Diabetic Patients With β-Glucosidase Inhibition , 1998, Diabetes Care.

[32]  C. Rattarasarn,et al.  Effect of acarbose in treatment of type II diabetes mellitus: a double-blind, crossover, placebo-controlled trial. , 1998, Journal of the Medical Association of Thailand = Chotmaihet thangphaet.

[33]  S. Haffner,et al.  Long-Term Titrated-Dose α-Glucosidase Inhibition in Non-Insulin-Requiring Hispanic NIDDM Patients , 1998, Diabetes Care.

[34]  M. Spengler,et al.  Efficacy of 24-week monotherapy with acarbose, metformin, or placebo in dietary-treated NIDDM patients: the Essen-II Study. , 1997, The American journal of medicine.

[35]  T. Čabrijan,et al.  Multicentric clinical trial to assess efficacy and tolerability of acarbose (Bay G 5421) in comparison to glibenclamide and placebo , 1997 .

[36]  M. Hanefeld,et al.  Glibenclamide, but Not Acarbose, Increases Leptin Concentrations Parallel to Changes in Insulin in Subjects With NIDDM , 1997, Diabetes Care.

[37]  G. Schernthaner,et al.  The Efficacy and Safety of Miglitol Therapy Compared With Glibenclamide in Patients With NIDDM Inadequately Controlled by Diet Alone , 1997, Diabetes Care.

[38]  Cindy Farquhar,et al.  3 The Cochrane Library , 1996 .

[39]  A. Calle-Pascual,et al.  Influence of 16-week monotherapy with acarbose on cardiovascular risk factors in obese subjects with non-insulin-dependent diabetes mellitus: a controlled, double-blind comparison study with placebo. , 1996, Diabetes & metabolism.

[40]  H. Shamoon,et al.  The Pharmacological Treatment of Hyperglycemia in NIDDM , 1996, Diabetes Care.

[41]  J. A. Hunt,et al.  A Double-Blind Placebo-Controlled Trial Evaluating the Safety and Efficacy of Acarbose for the Treatment of Patients With Insulin-Requiring Type II Diabetes , 1995, Diabetes Care.

[42]  G. Pagano,et al.  Comparison of miglitol and glibenclamide in diet-treated type 2 diabetic patients. , 1995, Diabete & metabolisme.

[43]  J. McGill,et al.  Reduction of Glycosylated Hemoglobin and Postprandial Hyperglycemia by Acarbose in Patients With NIDDM: A placebo-controlled dose-comparison study , 1995, Diabetes Care.

[44]  G. Bray,et al.  Multicenter, placebo-controlled trial comparing acarbose (BAY g 5421) with placebo, tolbutamide, and tolbutamide-plus-acarbose in non-insulin-dependent diabetes mellitus. , 1995, The American journal of medicine.

[45]  A. Leiva,et al.  Efficacy and tolerability of miglitol in the treatment of patients with non-insulin-dependent diabetes mellitus , 1995 .

[46]  S. Ross,et al.  The Efficacy of Acarbose in the Treatment of Patients with NonInsulin-Dependent Diabetes Mellitus: A Multicenter, Controlled Clinical Trial , 1994, Annals of Internal Medicine.

[47]  R. Coniff,et al.  Long-term efficacy and safety of acarbose in the treatment of obese subjects with non-insulin-dependent diabetes mellitus. , 1994, Archives of internal medicine.

[48]  M. Spengler,et al.  Efficacy of 24-Week Monotnerapy With Acarbose, Glibenclamide, or Placebo in NIDDM Patients: The Essen Study , 1994, Diabetes Care.

[49]  N. Hotta,et al.  Long‐term Effect of Acarbose on Glycaemic Control in Non‐insulin‐dependent Diabetes Mellitus: A Placebo‐controlled Double‐blind Study , 1993, Diabetic medicine : a journal of the British Diabetic Association.

[50]  J. Proietto,et al.  Low-Dose Acarbose Improves Glycemic Control in NIDDM Patients Without Changes in Insulin Sensitivity , 1993, Diabetes Care.

[51]  P. Brunetti,et al.  Efficacy and safety of two different dosages of acarbose in non-insulin dependent diabetic patients treated by diet alone , 1993 .

[52]  M. Spengler,et al.  Efficacy of 6 months monotherapy with glucosidase inhibitor Acarbose versus sulphonylurea glibenclamide on metabolic control of dietary treated type II diabetics (NIDDM). , 1992, Hormone and metabolic research. Supplement series.

[53]  R. Holman,et al.  Post-prandial glycaemic reduction by an alpha-glucosidase inhibitor in type 2 diabetic patients with therapeutically attained basal normoglycaemia. , 1991, Diabetes research.

[54]  M. Hanefeld,et al.  Therapeutic Potentials of Acarbose as First-Line Drug in NIDDM Insufficiently Treated With Diet Alone , 1991, Diabetes Care.