Diabetes Care. 2005 Mar;28(3):736-44.
A systematic review of drug therapy to delay or prevent type 2 diabetes.
Padwal R, Majumdar SR, Johnson JA, Varney J, McAlister FA.
Department of Medicine, 2E3.22 Walter C. Mackenzie HSC, University of Alberta Hospital, 8440-112th St., Edmonton, AB, Canada, T6G 2B7.
OBJECTIVE: To systematically review the evidence for the prevention of type 2 diabetes by pharmacological therapies. RESEARCH DESIGN AND METHODS: Randomized controlled trials and cohort studies examining the effect of oral hypoglycemic agents, antiobesity agents, antihypertensive agents, statins, fibrates, and estrogen on the incidence of type 2 diabetes were identified from MEDLINE, EMBASE, the Cochrane Controlled Trials Registry, and searches of reference lists. Two reviewers independently assessed studies for inclusion and performed data extraction. RESULTS: Ten studies of oral hypoglycemic agents and 15 studies of nonoral hypoglycemic agents were found. Oral hypoglycemic agents and orlistat are the only drugs that have been studied in randomized controlled trials with diabetes incidence as the primary end point. In the largest studies of 2.5-4.0 years' duration, metformin (relative risk [RR] 0.69, 95% CI 0.57-0.83), acarbose (0.75, 0.63-0.90), troglitazone (0.45, 0.25-0.83), and orlistat (hazard ratio [HR] 0.63, 95% CI 0.46-0.86) have all been shown to decrease diabetes incidence compared with placebo; however, follow-up rates varied from 43 to 96%. Current evidence for statins, fibrates, antihypertensive agents, and estrogen is inconclusive. In addition, the critical question of whether drugs are preventing, or simply delaying, onset of diabetes remains unresolved. CONCLUSIONS: Currently, no single agent can be definitively recommended for diabetes prevention. Future studies should be designed with diabetes incidence as the primary outcome and should be of sufficient duration to differentiate between genuine diabetes prevention as opposed to simple delay or masking of this condition.

Am J Physiol Regul Integr Comp Physiol. 2005 Feb 17;
SEROTONIN-TYPE 3 RECEPTORS MEDIATE INTESTINAL POLYCOSE- AND GLUCOSE- INDUCED SUPPRESSION OF INTAKE.
Savastano DM, Carelle M, Covasa M.
Department of Nutritional Sciences, College of Health and Human Development, The Pennsylvania State University, University Park, PA, USA.
Ondansetron, a selective serotonin-type 3 (5-HT3) receptor antagonist, was used to test the hypothesis that duodenal infusion of isosmotic solutions of Polycose or its hydrolytic product glucose, suppressed intake through 5-HT3 receptors. Polycose suppressed sucrose intake across both concentrations infused (132mM, 7.6 +/- 0.6 ml; 263mM, 2.3 +/- 0.5 ml), compared to intake under control conditions (12.6 +/- 0.3 ml, P <0.001). Pretreatment with 1.0 mg/kg ondansetron attenuated reduction of sucrose intake induced only by the highest concentration of Polycose (4.6 +/- 0.8 ml, P=0.004). Dose response testing revealed that suppression of food intake by 263mM Polycose was attenuated by ondansetron administered at 1.0, 2.0, and 5.0mg/kg equally, but not when given at 0.125, 0.25, and 0.5 mg/kg. Acarbose, an alpha-glucosidase inhibitor, attenuated Polycose-induced suppression of food intake and pretreatment with 1.0 mg/kg ondansetron had no further effect. Suppression of intake following 990mM glucose, but not mannitol infusion, was attenuated by pretreatment with 1.0 mg/kg ondansetron. The competitive SGLT1 inhibitor, phloridzin had no effect on 60 min 990mM glucose-induced suppression of intake or the ability of ondansetron to attenuate this suppression of intake. Conversely, glucose-induced suppression of intake was attenuated by phloridzin at earlier time points, and further attenuated when rats were pretreated with 1.0 mg/kg ondansetron. Ondansetron administration alone had no effect on intake at any dose tested. We conclude that 5-HT3 receptors participate in the inhibition of food intake by intraduodenal infusion of carbohydrate solutions through a post-hydrolytic, preabsorptive mechanism.

Diabetes Metab. 2002 Jun;28(3):195-200.
Acarbose improves indirectly both insulin resistance and secretion in obese type 2 diabetic patients.
Delgado H, Lehmann T, Bobbioni-Harsch E, Ybarra J, Golay A.
Division of Therapeutic Education for Chronic Diseases, University Hospital Geneva, Switzerland.
BACKGROUND: Acarbose is an oral antidiabetic mainly acting on postprandial blood glucose, inhibiting alphaglucosidase. Through this mechanism, it could improve the peripheral insulin sensitivity and/or increase the insulin secretion. The aim of the present study is to assess the therapeutic efficacy of Acarbose in obese type 2 diabetic patients on both insulin resistance and insulin secretion. METHODS: 17 obese non insulin-dependent diabetic patients, well controlled with diet alone were randomized into 2 groups: acarbose (2 x 50 mg) or placebo during 16 weeks. A glucagon test allowed to evaluate insulin secretion before and after treatment as well as a triple test (glucose-insulin-somatostatin) with indirect calorimetry allowed to evaluate insulin sensitivity. RESULTS: A significant improvement in post-prandial plasma glucose was detected only in the Acarbose group (8.0 +/- 0.5 mmol/l before vs 6.5 0.5 mmol/l after, p<0.05). Basal C-peptide secretion was similar between groups and remained unchanged after treatment. However, stimulated insulin secretion was significantly increased by 30%, p<0.05, in the Acarbose group while no change was detected in the placebo group. Interestingly, the group receiving Acarbose disclosed a 15% reduction in insulin resistance (15.0 +/- 1.8 mmol/l before vs 12.8 +/- 1.4 mmol/l after). CONCLUSIONS: Our results show that a treatment with Acarbose is efficient even in diabetic patients presenting a good glucose control without any other associated treatment. By decreasing post-prandial blood glucose, acarbose improves both insulin sensitivity and secretion.

Diabetes Obes Metab. 2001 Dec;3(6):423-7.
Effect of acarbose on weight maintenance after dietary weight loss in obese subjects.
Hauner H, Petzinna D, Sommerauer B, Toplak H.
German Diabetes Research Institute at the Heinrich-Heine-University Dusseldorf, Germany.
AIMS: Acarbose is a well established antidiabetic drug and is known to exert a modest weight-lowering effect. The aim of this study was to assess the potential of acarbose to improve weight maintenance after a substantial weight loss by dietary measures in obese subjects. DESIGN: Randomised, double-blind, placebo-controlled trial of the effect of acarbose on weight change over a 6-month follow-up period. PATIENTS AND METHODS: One hundred and ten obese subjects with a BMI > or = 32 and < or = 38 kg/m2 were included in the study and underwent a 10-16-week very-low-calorie diet programme to initiate weight loss. Then, subjects were randomised to receive either acarbose or placebo for 26 +/- 2 weeks. The primary variable was body weight. The primary efficacy analysis was performed in the per-protocol population (n = 75). RESULTS: After an initial mean weight loss of 10.0 +/- 3.4 kg, 54 subjects received acarbose at increasing dosage and 56 subjects received placebo treatment. After 14 weeks of follow-up, there was no change in body weight in the two groups. After 26 weeks, completed by 37 subjects in the acarbose group and by 38 subjects in the placebo group, a small weight regain of 0.6 kg was documented in the latter, whereas no weight increase was observed under acarbose treatment (p = 0.38, analysis of covariance with initial body weight as covariable). CONCLUSION: In obese individuals who undergo a hypocaloric diet and achieve a substantial loss of body weight, acarbose treatment provides only a very modest, not significant benefit to stabilise weight reduction. Thus, acarbose is not a useful adjunct to improve weight maintenance in obese subjects after weight loss.

JAMA. 2003 Jul 23;290(4):486-94.
Acarbose treatment and the risk of cardiovascular disease and hypertension in patients with impaired glucose tolerance: the STOP-NIDDM trial.
Chiasson JL, Josse RG, Gomis R, Hanefeld M, Karasik A, Laakso M; STOP-NIDDM Trial Research Group.
Research Centre, Centre Hospitalier de l'Universite de Montreal-Hotel-Dieu and Department of Medicine, Universite de Montreal, Montreal, Quebec, Canada.
CONTEXT: The worldwide explosive increase in type 2 diabetes mellitus and its cardiovascular morbidity are becoming major health concerns. OBJECTIVE: To evaluate the effect of decreasing postprandial hyperglycemia with acarbose, an alpha-glucosidase inhibitor, on the risk of cardiovascular disease and hypertension in patients with impaired glucose tolerance (IGT). DESIGN, SETTING, AND PARTICIPANTS: International, multicenter double-blind, placebo-controlled, randomized trial, undertaken in hospitals in Canada, Germany, Austria, Norway, Denmark, Sweden, Finland, Israel, and Spain from July 1998 through August 2001. A total of 1429 patients with IGT were randomized with 61 patients (4%) excluded because they did not have IGT or had no postrandomization data, leaving 1368 patients for a modified intent-to-treat analysis. Both men (49%) and women (51%) participated with a mean (SD) age of 54.5 (7.9) years and body mass index of 30.9 (4.2). These patients were followed up for a mean (SD) of 3.3 (1.2) years. INTERVENTION: Patients with IGT were randomized to receive either placebo (n = 715) or 100 mg of acarbose 3 times a day (n = 714). MAIN OUTCOME MEASURES: The development of major cardiovascular events (coronary heart disease, cardiovascular death, congestive heart failure, cerebrovascular event, and peripheral vascular disease) and hypertension (> or =140/90 mm Hg). RESULTS: Three hundred forty-one patients (24%) discontinued their participation prematurely, 211 in the acarbose-treated group and 130 in the placebo group; these patients were also followed up for outcome parameters. Decreasing postprandial hyperglycemia with acarbose was associated with a 49% relative risk reduction in the development of cardiovascular events (hazard ratio [HR], 0.51; 95% confidence interval [CI]; 0.28-0.95; P =.03) and a 2.5% absolute risk reduction. Among cardiovascular events, the major reduction was in the risk of myocardial infarction (HR, 0.09; 95% CI, 0.01-0.72; P =.02). Acarbose was also associated with a 34% relative risk reduction in the incidence of new cases of hypertension (HR, 0.66; 95% CI, 0.49-0.89; P =.006) and a 5.3% absolute risk reduction. Even after adjusting for major risk factors, the reduction in the risk of cardiovascular events (HR, 0.47; 95% CI, 0.24-0.90; P =.02) and hypertension (HR, 0.62; 95% CI, 0.45-0.86; P =.004) associated with acarbose treatment was still statistically significant. CONCLUSION: This study suggests that treating IGT patients with acarbose is associated with a significant reduction in the risk of cardiovascular disease and hypertension.

Diabetes Res Clin Pract. 2003 Jan;59(1):37-42.
Acarbose in the treatment of elderly patients with type 2 diabetes.
Josse RG, Chiasson JL, Ryan EA, Lau DC, Ross SA, Yale JF, Leiter LA, Maheux P, Tessier D, Wolever TM, Gerstein H, Rodger NW, Dornan JM, Murphy LJ, Rabasa-Lhoret R, Meneilly GS.
Division of Endocrinology and Metabolism, University of Toronto, Ont, Canada.
AIMS: To study the effect of acarbose, an alpha-glucosidase inhibitor, on glycemic control in elderly patients with type 2 diabetes. METHODS: Elderly patients with type 2 diabetes treated with diet alone were randomly treated in a double-blind fashion with placebo (n=99) or acarbose (n=93) for 12 months. RESULTS: After 12 months of therapy, there was a statistically significant difference in the change in glycated haemoglobin (HbA(1c)) (-0.6%) in the acarbose group versus placebo, as well as in the incremental post-prandial glucose values (-2.1 mmol h/l) and mean fasting plasma glucose (-0.7 mmol/l). Although there was no effect of acarbose on insulin release, there was a clear effect of acarbose to decrease relative insulin resistance (-0.8) (HOMA method). In addition, acarbose was generally well tolerated and safe in the elderly; most discontinuations were due to gastrointestinal side effects such as flatulence and diarrhea. There were no cases of hypoglycemia reported, and no clinically relevant changes in laboratory abnormalities or vital signs during the study. CONCLUSIONS: Acarbose improves the glycemic profile and insulin sensitivity in elderly patients with type 2 diabetes who are inadequately controlled on diet alone.

J Gerontol A Biol Sci Med Sci. 2002 Feb;57(2):M111-4.
The effect of acarbose on the colonic transit time of elderly long-term care patients with type 2 diabetes mellitus.
Ron Y, Wainstein J, Leibovitz A, Monastirsky N, Habot B, Avni Y, Segal R.
Department of Gastroenterology, Wolfson Hospital, Holon, Israel.
BACKGROUND: Constipation is common in elderly patients with diabetes mellitus (DM); its prevalence is estimated as up to 60% among patients with diabetic neuropathy. Acarbose, an alpha-glucosidase inhibitor, has a beneficial role in controlling DM, although one of its side effects is diarrhea. This study evaluates the efficacy of acarbose in improving constipation using transit time (TT) studies in elderly long-term care (LTC) patients. METHODS: Twenty-eight patients with type 2 DM and constipation were recruited for the study. TT was measured by radiopaque markers and was calculated separately for the four segments of the colon (ascending, transverse, descending, and rectosigmoid) and for the total colonic transit time (CTT). Segmental TT and CTT were evaluated in each patient before and after 1 week, and again after 4 weeks of treatment with acarbose. RESULTS: The mean baseline CTT measured in patients was 202 plus minus 136 hours. After 1 and 4 weeks of acarbose treatment, the baseline CTT significantly decreased to 149 plus minus 107 hours and 161 plus minus 97 hours, respectively (p <.002). For each segment studied, the TT was shortened, but it reached significance for the ascending and transverse colon only (p <.02 and p <.03, respectively). The effect of diet composition was examined. The amount of fiber consumed correlated with shortened CTT, while fat tended to be in negative correlation with TT. CONCLUSIONS: Acarbose therapy reduced the extremely prolonged CTT in LTC diabetic persons with constipation. The drug could be useful in relieving constipation in these patients, in addition to its beneficial effect in the control of diabetes.

Eat Weight Disord. 1998 Mar;3(1):46-9.
Acarbose treatment in obesity: a controlled study.
Bayraktar F, Hamulu F, Ozgen AG, Yilmaz C, Tuzun M, Kabalak T.
Ege University Medical Faculty, Endocrinology Department, Bornova, Izmir, 35100 Turkey.
Acarbose is an alpha-glucosidase inhibitor which reversibly inhibits oligosaccharidase and disaccharidase at the brush border of the small intestine. The aim of this study was to observe its effectiveness in the treatment of obesity. METHODS: Two groups of 25 obese women were put on a 15 kcal/kg/day low-calorie diet for 12 weeks. One group (the study group) received 150 mg/day acarbose for the first 2 weeks and 300 mg/day acarbose for the remaining 10 weeks. The second group (controls) received no additional treatment. Body weight, BMI, skinfold thickness, serum lipids, OGTT, and insulin and C-peptide responses to OGTT were assessed before and after the study. RESULTS: Body weight, BMI and skinfold thickness decreased significantly in both groups. Basal insulin and triglyceride levels in the study group, total and LDL cholesterol and triglyceride levels in the control group decreased significantly. No difference was found between the two groups when these decrements were compared, but the triglyceride level fell more in the control group. CONCLUSION: Additional acarbose therapy is not more beneficial than low-calorie diet therapy alone.

Diabetes Obes Metab. 2000 Jan;2(1):33-8.
Treatment of familial hypertriglyceridaemia with acarbose.
Malaguarnera M, Giugno I, Ruello P, Maugeri D, Pistone G.
Department of Internal Medicine and Geriatrics, University of Catania, Italy.
AIM: The evaluation of serum triglyceride levels has played an important role as an independent method for assessing the risk factor for coronary atherosclerosis. Fibrates, nicotinic acid, and omega-3 polyunsaturated fish oils are the pharmacological tools most used today against hypertriglyceridaemia. Acarbose is a pseudotetrasaccharide of microbial origin which exerts a competitive, selective and reversible inhibition of the intestinal alpha glucoside-hydrolase. We evaluated the efficacy and side-effects of acarbose as a new and alternative drug in the treatment of hypertriglyceridaemia in non-diabetic patients. METHODS: We enrolled 30 non-diabetic patients (18 men, 12 women; mean age 59.23 +/- 6.27 years) without a family history of diabetes mellitus affected by familial hypertriglyceridaemia. The study covered a total period of 6.5 months: half of the patients were on 1.5 months of 'run in' diet only followed by 5 months of therapeutic diet plus acarbose; and half were on the therapeutic diet plus placebo. We gave 30 dividable pills to all patients. The administration was as follows: half a pill before lunch and half a pill before dinner while on the 'run in' diet. Fifteen patients (group A) took acarbose while the reminder (group B) took a placebo (50 mg of starch); these were distributed randomly and the test was double blind. The 20 weeks of study were divided in five 4-week periods. Fasting serum concentrations of total cholesterol, triglycerides, HDL-cholesterol (HDL-c), LDL-cholesterol (LDL-c) and glucose were determined at the starting of the study and after each treatment cycle. Glucose values were determined 2 h after lunch at the beginning of the study and at the end of the first, third and fifth month of treatment. All parameters assessed have been analysed by anova. RESULTS: The serum total cholesterol, LDL-c levels observed in the two groups did not change during the course of treatment. We observed a noteworthy progressive reduction of mean baseline triglyceride levels until the fourth month (p < 0.05) in acarbose-treated patients, with an increase in HDL-c (p < 0.008). CONCLUSIONS: We maintain that acarbose may be a useful therapeutic tool in addition to the diet in order to reduce triglyceride serum levels in non-diabetic patients.

Diabetes Nutr Metab. 1999 Aug;12(4):277-85.
Effects of acarbose treatment in Type 2 diabetic patients under dietary training: a multicentre, double-blind, placebo-controlled, 2-year study.
Hasche H, Mertes G, Bruns C, Englert R, Genthner P, Heim D, Heyen P, Mahla G, Schmidt C, Schulze-Schleppinghof B, Steger-Johannsen G.
Bayer Vital GmbH & Co. KG, PH-Medizin Stoffwechsel, Leverkusen, Germany.
This 24-months, placebo-controlled, double-blind, randomised, group comparison study investigated the effect of acarbose vs placebo for improving metabolic control in patients with Type 2 diabetes under dietary training insufficiently controlled by diet alone. Patients randomised to acarbose had their dose increased in a stepwise manner to week 5. From week 5 onwards, they received 100 mg three times daily. This incremental dosing scheme was matched in the placebo group. All patients received specialist, intensive, continuous dietary training and counselling throughout the 2 yr of the study. Of the 74 patients randomised, 60 were included in the per-protocol analysis (28 receiving acarbose; 32 receiving placebo). HbA1c was the primary target variable. Per-protocol analysis found that, after 24 months, the mean difference in HbA1c relative to baseline value was -1.71+/-1.6% in the acarbose group and -0.82+/-1.1% in the placebo group. End-point values were 6.85+/-1.7% in the acarbose group and 7.41+/-1.1% in the placebo group. This difference between acarbose and placebo was statistically significant (p=0.02). Patients were defined as responders if they did not require additional treatment with an antidiabetic agent during the study. The responder rate under acarbose therapy was 89%, compared with 47% for placebo (p=0.0005). Acarbose-treated responders improved their HbA1c level to 6.45+/-0.82% after 24 months. The efficacy of acarbose was consistent throughout the study; decreasing efficacy was not evident. The results demonstrate the efficacy of acarbose for improving metabolic control in patients with Type 2 diabetes, even when such patients receive good dietary treatment and counselling.

Med Klin. 1998 Nov 15;93(11):651-5.
Continuous blood glucose monitoring: the acute effect of acarbose on blood glucose variations.
Herrmann BL, Schatz H, Pfeiffer A.
Universitatsklinikum Essen, Zentrum fur Innere Medizin, Abteilung fur Endokrinologie.
BACKGROUND: Acarbose, a pseudo-tetrasaccharid, inhibits intestinal alpha-glucosidases, effects a reduction of postprandial hyperglycemia and is particularly used in the treatment of patients with type-2 diabetes mellitus. The aim of the study is to analyse by a continuous blood glucose measurement the acute effect of acarbose after a carbohydrate loading and during a 12 hours period. PATIENTS AND METHODS: We examined 10 patients with type-2 diabetes mellitus (mean age 59.2 +/- 3.79, HbA1 9.2 +/- 0.26%) treated with sulfonylureas and/or insulin after a carbohydrate meal and 12 hours during daytime, to test whether the first application of acarbose influences the mean blood glucose or the blood glucose amplitudes. Four measurements were enrolled using a portable continuous blood glucose sensor (Glucosensor, unitec Ulm). A measurement after a carbohydrate loading (Fresubin, 500 kcal, 69 g carbohydrate) with 100 mg acarbose (Glucobay) was followed by a 12-hour measurement during daytime with 3 x 100 mg acarbose and standard diet. These measurements were repeated without acarbose. RESULTS: After a carbohydrate loading, the mean blood glucose level (AUC 44,320 +/- 10,660 with acarbose vs. 61,390 +/- 12,590 without acarbose; mean + SD; p = 0.004) decreased by 28%. During daytime blood glucose levels were not significantly decreased (165.7 +/- 50.3 mg/dl vs 183.7 + 67.4 mg/dl; p = 0.1) although the postprandial blood glucose amplitudes after the 3 meals were reduced significantly (85.90 +/- 24.6 mg/dl vs 106.5 +/- 20.5 mg/dl; p = 0.02). CONCLUSIONS: Continuous blood glucose monitoring indicated that acarbose diminished mean blood glucose levels after a carbohydrate loading in patients with type-2 diabetes mellitus, but not during 12 hours of standard diet, although blood glucose amplitudes decreased. Long-term improvements of metabolism by acarbose may therefore be related to the reduction of blood glucose amplitudes which is likely to reduce toxic effects of glucose on islet cell function.

Clin Ther. 1997 Jul-Aug;19(4):720-9.
Comparison of the effects of acarbose and voglibose in healthy subjects.
Kageyama S, Nakamichi N, Sekino H, Nakano S.
Division of Clinical Pharmacology and Therapeutics, Jikei University School of Medicine, Tokyo, Japan.
Acarbose and voglibose are alpha-glucosidase inhibitors. Although the pharmacologic effects and incidence of abdominal adverse events associated with the two drugs have been reported to differ, no study has directly compared acarbose and voglibose. To compare the pharmacologic effects and gastrointestinal adverse events associated with the two drugs, a randomized, placebo-controlled, double-masked, fivefold crossover study was performed in 20 healthy male subjects. To assess the pharmacologic effects, plasma immunoreactive insulin (IRI), plasma glucose, and 24-hour urinary connecting-peptide immunoreactivity (CPR) excretion were measured. Although the postprandial increase in plasma glucose level was reduced significantly with both acarbose and voglibose, the rate of reduction was small. The maximum concentration (Cmax) and area under the plasma concentration-time curve (AUC) of plasma IRI after meals decreased significantly with all treatments except voglibose 0.3 mg compared with placebo. Overall, the Cmax and AUC of plasma IRI decreased more when subjects received acarbose than voglibose. Urinary CPR excretion decreased by 30.6% and 41.7%, respectively, in subjects who received acarbose 50 mg or 100 mg compared with the previous day when no drug was given, whereas the urinary CPR excretion did not decrease significantly with voglibose. There was no significant difference in the frequency of gastrointestinal adverse events between groups, including the placebo group. One-day administration of acarbose and voglibose at currently recommended clinical doses demonstrated that acarbose was more effective in sparing endogenous insulin secretion than was voglibose.