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Background: Glycemic variability, an HbA1c-independent risk factor, has more deleterious effects than sustained hyperglycemia in the development of diabetic complications. This study analyzed the characteristics of glycemic variability in type 2 diabetes mellitus (T2DM) with HbA1c < 6.5% in duration of twice daily premixed insulin treatment and the effect of further treatment with acarbose., Methods: Eighty-six T2DM patients who used premixed insulin analogue (insulin aspart 30) twice daily and had HbA1c < 6.5% and 20 controlled subjects with normal glucose regulation (NGR) were monitored using the continuous glucose monitoring (CGM) system. The mean amplitude of glycemic excursions (MAGE), mean of daily differences (MODD) were used for assessing intra-day, inter-day glycemic variability. Hypoglycemia was defined as glucose level < 3.9 mmol/L for at least 15 minutes in CGM. According to reference values of MAGE, T2DM patients were classified into two groups: low-MAGE group with MAGE < 3.4 mmol/L (L-MAGE) and high-MAGE group with MAGE ≥ 3.4 mmol/L (H-MAGE). H-MAGE group received further treatment with acarbose for 2 weeks and was monitored a second time with CGM system., Results: After first CGM, L-MAGE group had 41 cases, and H-MAGE group had 45 cases. The MAGE and MODD of T2DM group were all higher than those of subjects with NGR (P < 0.01). Twenty-four percent (n = 11) in H-MAGE group had a total of 13 hypoglycemic events, 10 of the 13 events occurred at night, meanwhile 5% (n = 2) in L-MAGE group had a total of 2 hypoglycemic events, which also occurred at night (hypoglycemic events: 24% vs. 5%, χ(2) = 6.40, P < 0.01). MAGE value was correlated with hypoglycemia value and 2-hour postprandial plasma glucose value (r = -0.32 and 0.26, respectively, P < 0.05). After further acarbose therapy and secondly CGM, MAGE and MODD values in H-MAGE group were all significantly decreased (40%, P < 0.01, and 15%, P < 0.05, respectively), but remained higher than in the subjects with NGR (P < 0.05); 2% (n = 1) had a total of 1 hypoglycemic event, incidence significantly decreased (2% vs. 24%, χ(2) = 9.61, P < 0.01)., Conclusions: CGM system can detect the glycemic variability and asymptomatic hypoglycemic events of T2DM with well-controlled HbA1c in duration of insulin treatment. Combination therapy of premixed insulin twice daily with acarbose can flat glycemic variability and decrease hypoglycemic events.

Objective: The present study was a prospective, parallel group, open-labeled, comparative, multicentric, active controlled study to evaluate the safety, tolerability and benefits of fixed dose combination of acarbose and metformin versus metformin alone in type 2 diabetic patients., Methods: A total of 229 patients with type 2 diabetes were enrolled at 5 medical centers across India. They received either acarbose (50 mg) + metformin (500 mg) bid/tid (n=115) or metformin monotherapy (500 mg) bid/ tid (n=114) for 12 weeks. Primary objective was to evaluate safety and tolerability based on the adverse events reported. Secondary objective was efficacy assessment based on changes in fasting, post prandial blood glucose and HbA1c values., Results: In the acarbose + metformin group 10 patients reported 14 adverse events while in metformin group 9 patients reported 10 adverse events. No patient reported any serious adverse event or was withdraw from study because of adverse events. In the acarbose plus metformin group fasting blood glucose (FBG) decreased from a baseline of 158.85 +/- 18.14 mg/dl to 113.55 +/- 19.38 mg/dl (p < 0.0001) (decrease of 45.30 +/- 15.30 mg/dl) at 12 weeks, while in the metformin group fasting blood glucose decreased from a baseline of 158.31 +/- 26.53 mg/dl to 130.55 +/- 28.31 mg/dl (p < 0.0001) (decrease of 27.76 +/- 22.91 mg/dl) at 12 weeks. In the acarbose plus metformin group postprandial blood glucose (PPBG) decreased from a baseline of 264.65 +/- 34.03 mg/dl to 173.22 +/- 31.40 mg/dl (p < 0.0001) (decrease of 91.43 +/- 28.65 mg/dl) at 12 weeks, while in the metformin group PPBG decreased from a baseline of 253.56 +/- 36.28 mg/dl to 205.36 +/- 39.49 mg/dl (p < 0.0001) (decrease of 48.20 +/- 32.72 mg/dl) at 12 weeks. In the acarbose plus metformin group glycosylated haemoglobin (HbA1c) decreased from a baseline of 9.47 +/- 0.69% to 7.71 +/- 0.85% (p < 0.0001) (% decrease of 1.76 +/- 1.11) at 12 weeks, while in the metformin group HbAlc decreased from a baseline of 9.32 +/- 0.65% to 8.26 +/- 0.68% (p < 0.0001) (% decrease of 1.06 +/- 0.66) at 12 weeks. The combination of acarbose and metformin was found to be significantly superior in lowering the FBC (p < 0.0001), PPBG (p < 0.0001) and HbA1c (p < 0.0001) at 12 weeks as compared to metformin monotherapy., Conclusions: Fixed dose combination of acarbose and metformin was well tolerated and it was superior to metformin monotherapy in controlling FBG, PPBG and HbA(1C) levels in Type 2 Diabetes Mellitus patients.

What Is Known: The increased risk of cardiovascular events in diabetic patients has been related to numerous metabolic and haemoreological factors. Some of these factors appear to be particularly evident during the post-prandial phases and to be related to peak plasma glucose level., Aim: To compare the effect of addition of pioglitazone and acarbose to sulphonylureas and metformin therapy on metabolic parameters and on markers of endothelial dysfunction and vascular inflammation in type 2 diabetic patients., Materials and Methods: We enrolled 473 caucasian type 2 diabetic patients. All patients underwent measurements of height and body weight, body mass index (BMI), glycated haemoglobin (HbA1c) , fasting plasma glucose (FPG), post-prandial plasma glucose (PPG), fasting plasma insulin (FPI), post-prandial plasma insulin (PPI), homeostasis model assessment (HOMA index), systolic blood pressure (SBP), diastolic blood pressure (DBP), total cholesterol (TC), low density lipoprotein-cholesterol (LDL-C), high density lipoprotein-cholesterol (HDL-C), triglycerides (Tg), sICAM-1, IL-6, high-sensitivity C reactive protein (hsCRP), sVCAM-1, sE-selectin and tumour necrosis factor (TNF-α). Assessments were made at start of titration, after 3 months [before a first oral glucose tolerance test (OGTT)], after 6 months and at the study end (before a second OGTT)., Results: Two-hundred and seventy four patients completed the study: 138 were randomized to double-blind treatment with pioglitazone and 136 with acarbose. Significant BMI and weight increase were observed after full treatment in the pioglitazone group relative to the acarbose group. A decrease in glycated haemoglobin was observed after the titration period in the pioglitazone group compared to both baseline value and the acarbose group. A decrease in glycated haemoglobin was also obtained after full treatment in the pioglitazone group when compared to the end of titration period and to the acarbose group. Significant decrease in FPG was obtained in the pioglitazone group after full treatment compared to the end of titration period. Post-prandial plasma glucose decrease was observed in acarbose group compared to the baseline value and to the end of titration period. Fasting plasma insulin decreased in the pioglitazone group after both the titration period and the full treatment period compared to both the baseline value and the acarbose group. The HOMA index decreased significantly after the full treatment in pioglitazone group compared to the end of titration period and to the acarbose group. Interleukin-6 and tumour necrosis factor-α decreased after full treatment in the pioglitazone group relative to the end of titration period. Significant hsCRP decrease was obtained after the titration period when compared to the baseline value in the pioglitazone group. High-sensitivity C reactive protein decreased in the pioglitazone group after full treatment compared to the end of titration period and to the acarbose group., What Is New and Conclusion: Pioglitazone reduces the inflammatory response to a glucose challenge more than acarbose in type 2 diabetic patients, already treated with maximal doses of sulphonylureas and metformin., (Copyright © 2010 Blackwell Publishing Ltd.)

The objective of this study was to investigate the effect of metformin versus acarbose in terms of ovulation rate, their impact on hormonal and metabolic status and tolerability of both drugs in patients with polycystic ovary syndrome (PCOS). Seventy-five patients with PCOS were included in this prospective randomised controlled double-blinded clinical study. According to randomisation, patients were allocated to receive either metformin 2550 mg/day (n = 37) or acarbose 300 mg/day (n = 38) for 12 weeks. Primary study outcomes were ovulation rate, restoration of a regular menstrual cycle and the incidence of side effects. Secondary outcomes included treatment-related hormonal and metabolic changes. Comparable high rates of regular menstrual cycles as well as ovulation could be achieved in both groups (70% and 73% for metformin vs. 78% and 59% for acarbose, p = 0.330 and p = 0.185, respectively). In contrast, only in patients treated with metformin a statistically significant decrease in fasting insulin and cholesterol levels as well as BMI was observed. However, comparing both groups at the end of treatment, no significant differences in metabolic and/or hormonal parameters could be detected. Regarding side effects, the rate of flatulence and/or diarrhoea was significantly lower for acarbose compared to metformin (38% vs. 80%, p < 0.001).

To decrease the risk of postprandial hyperglycemia and late hypoglycemia in elderly people with diabetes who eat rice porridge for breakfast, we administered 50mg acarbose to 30 elderly people with type 2 diabetes. The results demonstrated that acarbose could prevent the fluctuations in post-breakfast blood glucose levels., (Copyright (c) 2010 Elsevier Ireland Ltd. All rights reserved.)

Lifestyle changes and some drugs can help. Lifestyle interventions aimed at weight loss of 5% to 10% of body weight along with moderate aerobic exercise such as brisk walking for 150 minutes a week are the most effective means to prevent impaired fasting glucose (IFG) or impaired glucose tolerance (IGT) from progressing to diabetes (strength of recommendation [SOR]: A, several meta-analyses, including a recent Cochrane review).

Background: Insulin antibody (IAb) may be produced in patients receiving long-term, animal-derived insulin, leading to insulin resistance or hypoglycemia. There have been very few reports of hypoglycemia caused by IAb in patients taking recombinant human insulin., Case Report: We report the case of an 82-year-old male patient with type 2 diabetes mellitus who suffered repeated episodes of severe hypoglycemia-related symptoms (including coma) prior to admission. The patient had been taking Novolin 30R, a premixed human insulin. The patient's IAb level was markedly elevated, and hypoglycemia caused by recombinant human insulin treatment-induced IAb production was diagnosed. Acarbose and metformin were prescribed, and the patient recovered uneventfully. The patient ceased taking these medications, and he was subsequently treated with recombinant human insulin to combat hyperglycemia. This was followed by reoccurrence of hypoglycemic coma. The patient was advised to avoid taking recombinant human insulin for the rest of his life and to control hyperglycemia with acarbose and metformin., Conclusions: Although rare, hypoglycemia caused by recombinant human insulin-induced IAb production should be considered in patients with type 2 diabetes who experience repeated episodes of hypoglycemia.

Diabetes mellitus leads to the development of a host of micro- and macrovascular complications, which collectively lead to substantial morbidity and mortality. Among the microvascular complications of diabetes, diabetic kidney disease is the most common. Macrovascular complications from diabetes lead to a 2- to 4-fold increase in the incidence of cardiovascular disease and up to twice the mortality from cardiovascular causes as compared with nondiabetic individuals. This article discusses the various drug classes used to treat diabetes mellitus, and reviews the current clinical evidence linking glycemic control using these drug classes on diabetic kidney and cardiovascular disease., (2010 Elsevier Inc. All rights reserved.)

1. The aim of the present study was to compare the effects of glipizide controlled-release (CR) tablets monotherapy with that of glipizide CR tablets plus acarbose on glycaemic variability in newly diagnosed Type 2 diabetes (T2DM) patients using a continuous glucose-monitoring system (CGMS). 2. Forty newly diagnosed T2DM patients whose glycated haemoglobin A1c (HbA1c) levels ranged from 7.0% to 9.8% were randomized to either monotherapy or combination therapy. Overall glycaemic control and blood glucose variability were evaluated by CGMS parameters. 3. After 8 weeks treatment, fasting and postprandial blood glucose, HbA1c, glycated albumin (GA), mean blood glucose (MBG), mean amplitude of glycaemic excursions (MAGE), postprandial incremental area under the curve (AUC(pp)) and homeostasis model assessment of insulin resistance decreased significantly in both groups (P < 0.01). There was also a significant decrease in the mean of daily differences (MODD) in the combination therapy group. Mean changes in MBG, MAGE, MODD and AUC(pp) were significantly greater in the combination therapy group than in the monotherapy group (all P < 0.01), whereas no significant differences were found in the mean changes of HbA1c and GA. Multivariate regression analysis showed that the decrement in AUC(pp) was significantly associated with decreases in MAGE. 4. In conclusion, glipizide CR tablets alone or in combination with acarbose can improve overall blood glucose levels and glycaemic variability. Combination therapy using glipizide CR tablets and acarbose was more effective in reducing intraday and day-to-day glycaemic variability than glipizide CR tablet monotherapy.

Background: Chronic hyperglycemia is a major contributor to in vivo platelet activation in diabetes mellitus., Objectives: To evaluate the effects of acarbose, an alpha-glucosidase inhibitor, on platelet activation and its determinants in newly diagnosed type 2 diabetic patients., Methods: Forty-eight subjects (26 males, aged 61 +/- 8 years) with early type 2 diabetes (baseline hemoglobin A(1c) < or = 7% and no previous hypoglycemic treatment) were randomly assigned to acarbose up to 100 mg three times a day or placebo, and evaluated every 4 weeks for 20 weeks. The main outcome measures were urinary 11-dehydro-thromboxane (TX)B(2) (marker of in vivo platelet activation) and 8-iso-prostaglandin (PG)F(2alpha) (marker of in vivo lipid peroxidation) excretion rate, 2-h postprandial plasma glucose (PPG) after a test meal, and assessment of glucose fluctuations by mean amplitude of glycemic excursions (MAGE)., Results: Baseline measurements revealed biochemical evidence of enhanced lipid peroxidation and platelet activation. As compared with the placebo group, patients treated with acarbose had statistically significant reductions in urinary 11-dehydro-TXB(2) and 8-iso-PGF(2alpha) excretion rate as early as after 8 weeks and at each subsequent time point (between-group P < 0.0001 at 12, 16 and 20 weeks), following earlier decreases in PPG and MAGE. Multiple regression analyses in the acarbose group revealed that PPG was the only significant predictor of 11-dehydro-TXB(2) urinary excretion rate (beta = 0.39, P = 0.002) and MAGE the only predictor of 8-iso-PGF(2alpha) urinary excretion rate (beta = 0.42, P = 0.001)., Conclusions: Postprandial hyperglycemia is associated with enhanced lipid peroxidation and platelet activation in early type 2 diabetes. A moderate decrease in PPG achieved with acarbose causes time-dependent downregulation of these phenomena, suggesting a causal link between early metabolic abnormalities and platelet activation in this setting.

Background: For microvascular outcomes, there is compelling historical and contemporary evidence for intensive blood glucose reduction in patients with either type 1 diabetes mellitus (T1DM) or type 2 diabetes mellitus (T2DM). There is also strong evidence to support macrovascular benefit with intensive blood glucose reduction in T1DM. Similar evidence remains elusive for T2DM. Because cardiovascular outcome trials utilizing conventional algorithms to attain intensive blood glucose reduction have not demonstrated superiority to less aggressive blood glucose reduction (Action to Control Cardiovascular Risk in Diabetes; Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation; and Veterans Affairs Diabetes Trial), it should be considered that the means by which the blood glucose is reduced may be as important as the actual blood glucose., Methods: By identifying quantitative differences between antidiabetic agents on carbohydrate exposure (CE), hepatic glucose uptake (HGU), hepatic gluconeogenesis (GNG), insulin resistance (IR), peripheral glucose uptake (PGU), and peripheral insulin exposure (PIE), we created a pharmacokinetic/pharmacodynamic model to characterize the effect of the agents on the glucose supply and insulin demand dynamic. Glucose supply was defined as the cumulative percentage decrease in CE, increase in HGU, decrease in GNG, and decrease in IR, while insulin demand was defined as the cumulative percentage increase in PIE and PGU. With the glucose supply and insulin demand effects of each antidiabetic agent summated, the glucose supply (numerator) was divided by the insulin demand (denominator) to create a value representative of the glucose supply and insulin demand dynamic (SD ratio)., Results: Alpha-glucosidase inhibitors (1.25), metformin (2.20), and thiazolidinediones (TZDs; 1.25-1.32) demonstrate a greater effect on glucose supply (SD ratio >1), while secretagogues (0.69-0.81), basal insulins (0.77-0.79), and bolus insulins (0.62-0.67) demonstrate a greater effect on insulin demand (SD ratio <1)., Conclusion: Alpha-glucosidase inhibitors, metformin, and TZDs demonstrate a greater effect on glucose supply, while secretagogues, basal insulin, and bolus insulin demonstrate a greater effect on insulin demand. Because T2DM cardiovascular outcome trials have not demonstrated macrovascular benefit with more aggressive blood glucose reduction when using conventional algorithms that predominantly focus on insulin demand, it would appear logical to consider a model that incorporates both the extent of blood glucose lowering (hemoglobin A1c) and the means by which the blood glucose was reduced (SD ratio) when considering macrovascular outcomes., ((c) 2010 Diabetes Technology Society.)

The objective was to evaluate the effects of an inhibitor of alpha-amylase and glucosidase (acarbose, Pfizer Limited, Corby, UK) on ruminal fermentation, blood metabolism and microbial profile in dairy cows in a 2x2 cross-over experiment. Eight Holstein cows fitted with rumen cannulas (milk yield, 24.3+/-2.35 kg/d, body weight, 622+/-54 kg, days in milk, 183+/-67, 5 multiparous and 3 primiparous) were used. Treatments were: control (no additive, CTR) and alpha-amylase and glucosidase inhibitor (0.75 g acarbose-premix/cow per d, AMI). Animals were given ad-libitum access to a high non-fibre carbohydrate (NFC) partial mixed ration (PMR) containing 17.6% crude protein, 28.3% neutral detergent fibre, and 46.5% NFC in the dry matter and supplementary concentrate during milking. Blood samples were taken to determine blood glucose, insulin and urea within the first hour after the morning feeding on two separate days in each period. Samples of ruminal contents were collected during 3 d in each period at 0, 4 and 8 h after feeding to determine volatile fatty acid and ammonia-N concentrations and to quantify protozoa, Streptococcus bovis and Megasphaera elsdenii. Rumen pH was recorded electronically at 22-min intervals during 6 d in each period. Results were analysed using a mixed-effects model. Cows on AMI treatment spent less time with ruminal pH <5.6 compared with cows in the CTR group (3.74 and 6.52+/-0.704 h/d, respectively). Cows in the AMI group had greater daily average pH compared with those in the CTR group (6.05 and 5.92+/-0.042, respectively). AMI animals tended (P=0.09) to have lower Str. bovis to Meg. elsdenii ratio than CTR (4.09 and 26.8+/-12.0, respectively). These results indicate that dietary supplementation with acarbose in dairy cattle fed high-production rations may be effective in reducing the time for which rumen pH is suboptimal, with no negative effects on ruminal fermentation and blood metabolites.

Postprandial hyperglycemia (PPH) and intermittent hypoxia related to the sleep apnea syndrome are important predictors of cardiovascular disease. We investigated the effects of intermittent hypoxia on pathological changes in the left ventricular (LV) myocardium caused by PPH in lean mice and evaluated the influence of acarbose, an α-glucosidase inhibitor. Male C57BL/6J mice aged 8 weeks were exposed to intermittent hypoxia (8 h/day during the daytime) or kept under normoxia. PPH was induced by restriction of feeding to 1-h periods twice a day, with the restricted diet (RD) mice receiving either standard chow or chow containing 0.02% acarbose. Another group of mice were fed standard chow ad libitum (AL). Plasma glucose levels after food intake were significantly elevated in RD but not in AL mice, and glucose levels were suppressed by acarbose. Intermittent hypoxia exacerbated cardiomyocyte hypertrophy and interstitial fibrosis in the LV myocardium of RD mice. Superoxide production and expression of 4-hydroxy-2-nonenal in the LV myocardium with intermittent hypoxia were increased in RD mice, but not AL mice. In addition, expression of tumor necrosis factor α (TNF-α) mRNA was increased in hypoxic RD mice. Treatment with acarbose inhibited oxidative stress and TNF-α mRNA expression and preserved the histological architecture of the LV myocardium.

Platelet-derived microparticles (PDMP), selectins, and adiponectin play an important role in the development of atherosclerosis in diabetes. Acarbose has been shown to have a beneficial effect on postprandial hyperglycemia in diabetic patients. However, its influence on PDMP, selectins, and adiponectin in these patients is poorly understood. We investigated the effect of acarbose on circulating levels of PDMP, selectins, and adiponectin in patients with type 2 diabetes. Acarbose (300 mg/day) was administered for 3 months. Levels of PDMP, sP-selectin, sL-selectin, and adiponectin were measured by ELISA at baseline and after 1 and 3 months of treatment. The levels of PDMP, sP-selectin, and sL-selectin were higher in diabetic patients than in hypertensive patients (PDMP; 35.1 +/- 34.2 vs. 53.3 +/- 56.7 U/ml, P < 0.05: sP-selectin; 134 +/- 52 vs. 235 +/- 70 ng/dl, P < 0.01: sL-selectin; 569 +/- 183 vs. 805 +/- 146 ng/ml, P < 0.05), while there were no significant differences between hypertensive and hyperlipidemic patients. Before acarbose treatment, the adiponectin level of diabetic patients was lower than that of hypertensive patients. Acarbose therapy significantly decreased the plasma PDMP level relative to baseline. Acarbose also caused a significant decrease of sP-selectin and sL-selectin. On the other hand, acarbose therapy led to a significant increase of adiponectin after 3 months of administration compared with baseline (adiponectin: diabetes versus hypertension, 3.61 +/- 1.23 vs. 5.87 +/- 1.92 microg/ml, P < 0.05; diabetes versus controls, 2.81 +/- 0.95 vs. 6.13 +/- 1.24 microg/ml, P < 0.01). Twelve of the 30 diabetic patients had a history of thrombotic complications. Furthermore, the reduction of PDMP and selectins during acarbose therapy was significantly greater in the thrombotic group (12 of 30) than in the nonthrombotic group (18 of 30) of diabetic patients. Acarbose may be beneficial for primary prevention of atherothrombosis in patients with type 2 diabetes. However, it requires a large clinical trial to test this hypothesis.

Dumping syndrome is a frequent complication of esophageal, gastric or bariatric surgery. Rapid gastric emptying, with the delivery to the small intestine of a significant proportion of solid food as large particles that are difficult to digest, is a key event in the pathogenesis of this syndrome. This occurrence causes a shift of fluid from the intravascular component to the intestinal lumen, which results in cardiovascular symptoms, release of several gastrointestinal and pancreatic hormones and late postprandial hypoglycemia. Early dumping symptoms comprise both gastrointestinal and vasomotor symptoms. Late dumping symptoms are the result of reactive hypoglycemia. Besides the assessment of clinical alertness and endoscopic or radiological imaging, a modified oral glucose tolerance test might help to establish a diagnosis. The first step in treating dumping syndrome is the introduction of dietary measures. Acarbose can be added to these measures for patients with hypoglycemia, whereas several studies advocate guar gum or pectin to slow gastric emptying. Somatostatin analogs are the most effective medical therapy for dumping syndrome, and a slow-release preparation is the treatment of choice. In patients with treatment-refractory dumping syndrome, surgical reintervention or continuous enteral feeding can be considered, but the outcomes of such approaches are variable.

Epidemiologic studies suggest that postprandial hyperglycemia is more strongly linked to an increased risk for cardiovascular events than fasting or preprandial glucose levels. Although the results of prospective randomized studies proving causation of this finding are mixed, clinicians have given increased attention to target therapy to postprandial glucose than in the past. Rapid-acting insulin analogues, glucagon-like peptide-1 agonists, dipeptidyl peptidase-4 inhibitors, and acarbose all target the postprandial glucose levels. This wide range of therapies allows the clinician to mix and match agents of different classes to target the fasting, preprandial, and postprandial glucose to optimize the daily glucose pattern and reduce the risk of diabetic complications.

Background/aims: Non-alcoholic fatty liver disease (NAFLD) is a hepatic manifestation of metabolic syndrome that is closely associated with multiple factors such as obesity, hyperlipidemia, type 2 diabetes mellitus and hypertension, making it difficult to treat NAFLD effectively using any monotherapy available to date. In this study, we propose a novel combination therapy for NAFLD comprising ezetimibe (EZ), a cholesterol absorption inhibitor, and acarbose (AC), an alpha-glucosidase inhibitor., Methods: C57BL/6J mice were divided into five treatment groups as follows: basal diet (BD), high-fat diet (HFD) only, HFD with EZ (5mg/kg/day), HFD with AC (100mg/kg/day), and HFD with both EZ and AC for 24 weeks., Results: Long-term combination therapy with EZ and AC significantly reduced steatosis, inflammation and fibrosis in the liver, compared with long-term monotherapy with either drug, in an HFD-induced NAFLD mouse model; the combination therapy also significantly increased the expression of microsomal triglyceride transfer protein (MTP) and peroxisome proliferators-activated receptor-alpha1 (PPAR-alpha1) in the liver, compared with either monotherapy, which may have led to the improvement in lipid metabolic disorder seen in this model., Conclusions: Combination therapy with EZ and AC for 24 weeks improved the histopathological findings in a mouse model of NAFLD.

The alpha-glucosidase inhibitor acarbose is administered to control blood glucose levels in type 2 diabetic patients and, in several countries, in those with impaired glucose tolerance. The efficacy and safety of the drug has been well established in these patient populations. Acarbose shows no weakening of efficacy in long-term diabetes treatment, reduces the development of type 2 diabetes in those with impaired glucose tolerance, and also appears to reduce the risk of cardiovascular disease. The underlying mechanisms of its effect on the risk of developing macrovascular complications have still to be elucidated. The mode of action of acarbose, which precedes all other metabolic processes involved in blood glucose regulation, inhibits high increases in postprandial blood glucose. Due to this early mode of action, acarbose also modifies insulin and proinsulin secretion which are both involved in ss-cell dysfunction and insulin resistance and may be independent risk factors for cardiovascular mortality. Based on the literature available the present state of knowledge on insulin and proinsulin as risk factors for cardiovascular mortality is reviewed as well as the effect of acarbose on the regulation of the ss-cells as monotherapy and in combination regimens. Possible associated interactions with the cardiovascular system are identified.

Background: Acarbose, an antidiabetic drug, is an alpha-glucosidase inhibitor that can inhibit glucose absorption in the intestine. A recent large-scale clinical trial, STOP-NIDDM, showed that acarbose reduces the risk of myocardial infarction. We examined whether acarbose reduces myocardial infarct size and investigated its mechanisms., Methods and Results: Rabbits were fed with 1 of 2 diets in this study: normal chow, 30 mg acarbose per 100 g chow for 7 days. Rabbits were assigned randomly to 1 of 4 groups: control (n = 10), acarbose (n = 10), acarbose + 5HD (n = 10, intravenous 5 mg/kg of 5-hydroxydecanoate), and 5HD (n = 10, intravenous 5 mg/kg of 5HD). Rabbits then underwent 30 minutes of coronary occlusion followed by 48-hour reperfusion. Postprandial blood glucose levels were higher in the control group than in the acarbose group. The infarct size as a percentage of the left ventricular area at risk was reduced significantly in the acarbose (19.4% +/- 2.3%) compared with the control groups (42.8% +/- 5.4%). The infarct size-reducing effect of acarbose was abolished by 5HD (43.4% +/- 4.7%). Myocardial interstitial 2,5-dihydroxybenzoic acid levels, an indicator of hydroxyl radicals, increased during reperfusion after 30 minutes of ischemia, but this increase was inhibited in the acarbose group. This was reversed by 5HD., Conclusion: Acarbose reduces myocardial infarct size by opening mitochondrial KATP channels, which may be related to the prevention of postprandial hyperglycemia and hydroxyl radical production.

Introduction: In this study, we examined the effects of the alpha-glucosidase inhibitors acarbose and voglibose on postprandial plasma glucose and serum triglyceride levels in patients with type 2 diabetes mellitus., Methods: Twenty-one Japanese patients with type 2 diabetes were enrolled in this study. Subjects had been treated with voglibose for at least 3 months. They underwent a 400 kcal balanced food meal tolerance test before and 8 weeks after the changeover from voglibose to acarbose. Subjects were divided into two groups: the first group (low-dose group; n=11) was changed over from 0.6 mg/day voglibose to 150 mg/day acarbose, and the other (high-dose group; n=10) from 0.9 mg/day voglibose to 300 mg/day acarbose., Results: The increment rate of postprandial plasma glucose ([plasma glucose 2 hours after test meal - fasting glucose]/fasting glucose) decreased from 34.7%+/-23.9% to 25.0%+/-24.6% (P=0.13) in the low-dose group, and decreased significantly from 56.1%+/-53.1% to 31.5%+/-36.0% (P=0.03) in the high-dose group after changeover. However, there were no significant changes in blood glycated hemoglobin (HbA(1c)) levels before and after changeover in either group. The increment rate of postprandial serum triglyceride (TG) ([serum TG 2 hours after test meal - fasting TG]/fasting TG) decreased significantly only in the high-dose group (52.4%+/-60.0% to 24.3%+/-16.6%) (P=0.05). No significant changes in serum high-density lipoprotein cholesterol levels were observed in either group, whereas serum low-density lipoprotein cholesterol levels decreased significantly from 3.20+/-0.25 to 2.65+/-0.18 mmol/L (P=0.04), only in the high-dose group., Conclusions: In patients with type 2 diabetes our findings suggest that acarbose 300 mg/day is superior to voglibose 0.9 mg/day in improving postprandial hyperglycemia and hypertriglyceridemia.

A challenge model was used to evaluate a new approach to controlling acute acidosis. Acute acidosis reduces performance in both dairy and beef cattle and most often occurs as a consequence of ingestion of large amounts of readily fermentable starch, resulting in increased production of volatile fatty acids (VFA) and lactic acid and a reduction in ruminal pH. Acarbose is an alpha-amylase and glucosidase inhibitor that slows the rate of degradation of starch to glucose, thereby reducing the rate of VFA production and maintaining rumen pH at a more stable level. It is commercially available (Glucobay, Bayer, Wuppertal, Germany) and indicated for the control of blood glucose in diabetic patients. The ability of acarbose to reduce the incidence of acidosis and the comparative efficacies of acarbose, sodium bicarbonate, and monensin were tested in 3 acute acidosis challenge experiments in cattle. Rumen-cannulated Holstein steers were challenged with a mixture of 48.4% cornstarch, 48.4% ground corn, 2.1% sodium caseinate, and 1.1% urea with or without test substance. The challenge was administered at a rate of 12.5 g/kg of body weight (BW) as a slurry through the cannula directly into the rumen. Ruminal pH was monitored at 10-min intervals throughout the study. Animals were removed from study and rumen contents replaced if they exhibited acute acidosis as defined as pH <4.5. If acidosis was not observed within 24 h, animals were subjected to a second challenge. Ruminal fluid samples were taken for measurement of VFA and lactate concentrations at various intervals after the challenge. In experiment 1, the carbohydrate challenge induced acidosis in 4 of 4 control animals and 0 of 4 animals treated with 2.14 or 21.4 mg of acarbose/kg of BW in the challenge based on the criterion of pH <4.5. In experiment 2, the carbohydrate challenge induced acidosis in 4 of 7 control animals and 1 of 7 animals when 1.07 mg of acarbose/kg of BW was included in the challenge. In experiment 3, acidosis was induced in 7 of 7 animals in the control, 1% sodium bicarbonate, and 12 mg of monensin/kg of dry matter intake groups and in 3 of 8 steers administered 1.07 mg of acarbose/kg of BW in the challenge. Increases in lactate concentrations and decreases in total VFA associated with acute acidosis were mitigated by acarbose. Thus, acarbose, an amylase and glucosidase inhibitor, prevented or reduced the incidence of acidosis in an acute challenge model in steers and was more effective than monensin or sodium bicarbonate.

Objective: To compare the efficacy and tolerability of nateglinide with those of acarbose in Chinese type 2 diabetes mellitus (T2DM) patients., Methods: This multi-center, randomized, double-blind, parallel-arm study compared the efficacy and tolerability of nateglinide (120 mg, 3/d, n = 119) and those of acarbose (100 mg, 3/d, n = 118) during a 12-week treatment in T2DM patients uncontrolled by diet with glycosylated haemoglobin (HbA1c) 6.5% - 11.0%., Results: Monotherapy with nateglinide (120 mg, 3/d) or acarbose (100 mg, 3/d) decreased HbA1c to a similar extent during 12-week treatment. The mean change from baseline to end-point in HbA1c was (-0.90 +/- 0.98)% and (-0.83 +/- 0.81)% in patients receiving nateglinide and acarbose, respectively, with no significant difference between the two groups (P > 0.05). The decrease in fasting plasma glucose (FPG) was similar between nateglinide and acarbose (P > 0.05). The mean change in 2-hour postprandial plasma glucose (PG2h) was (-1.45 +/- 2.74) mmol/L and (-2.20 +/- 2.21) mmol/L in patients receiving nateglinide and acarbose (P = 0.0017). Body weight was significantly decreased in both groups at the end-point (P < 0.05), although the decrease was more with acarbose than nateglinide [(-0.66 +/- 1.79) kg vs (-2.06 +/- 2.00) kg, P = 0.0000]. And the proportion of patients experiencing any presumed drug related adverse events was not significantly different between the two groups., Conclusions: Nateglinide (120 mg, 3/d) is effective and well tolerated in T2DM patients uncontrolled by diet, demonstrating similar HbA1c reductions as compared with acarbose (100 mg, 3/d).

Objective: To compare the metabolic effects of acarbose and repaglinide in type 2 diabetic patients who are being treated with a sulphonylurea-metformin combination therapy. The primary endpoint of the study was to evaluate which add-on treatment between acarbose and repaglinide is more efficacious in reducing PPG. The second endpoint was to evaluate which of these two treatment is more efficacious in the global management of glucose homeostasis in the enrolled patients., Research Design and Methods: After a 4-week run-in period with a sulphonylurea-metformin combination, 103 patients were randomised to receive in addition either repaglinide, up to 6 mg/day (2 mg three times a day) or acarbose, up to 300 mg/day (100 mg three times a day) with forced titration (independently of their glycaemic control, unless side-effects developed due to the drug dosage) for 15 weeks. The treatment was then crossed-over for further 12 weeks until the 27th week. We assessed body mass index (BMI), glycosylated haemoglobin (HbA(1c)), fasting plasma glucose (FPG), postprandial plasma glucose (PPG), fasting plasma insulin (FPI), postprandial plasma insulin (PPI), homeostatic model assessment (HOMA) index, systolic blood pressure (SBP), diastolic blood pressure (DBP), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C) and triglycerides (Tg), at baseline and at 1, 2, 15 and 27 weeks of treatment., Results: Seven patients did not complete the study, comprising one patient who was lost to follow-up and a further six through side-effects (two in week 1, one in week 15 and three after cross-over) Side-effects were classified as nausea (one in acarbose group), gastrointestinal events (four in acarbose group), and hypoglycaemia (one in repaglinide group). After 15 weeks of therapy, the repaglinide-treated patients experienced a significant decrease in HbA(1c) (-1.1%, p < 0.05), FPG (-9.5%, p < 0.05), and PPG (-14.9%, p < 0.05), when compared to the baseline values. However, the same treatment was associated with a significant increase in body weight (+2.3%, p < 0.05), BMI (+3.3%, p < 0.05) and FPI (+22.5%, p < 0.05); The increase was reversed during the cross-over phase. After 15 weeks of therapy, the acarbose-treated patients experienced a significant decrease in body weight (-1.9%, p < 0.05), BMI (-4.1%, p < 0.05), HbA(1c) (-1.4%, p < 0.05), FPG (-10.7%, p < 0.05), PPG (-16.2%, p < 0.05), FPI (-16.1%, p < 0.05), PPI (-26.9%, p < 0.05), HOMA index (-30.1%, p < 0.05), when compared to the baseline values. All these changes were reversed during the cross-over study phase, except those relating to HbA(1c), FPG and PPG. The only changes that significantly differed when directly comparing acarbose- and repaglinide-treated patients were those relating to FPI (-16.1% vs. +22.5%, respectively, p < 0.05) and HOMA index (-30.1% vs. +2.7%, p < 0.05)., Conclusion: In addition from having a similar effect to repaglinide on PPG, acarbose appeared to have a more comprehensive positive effect on glucose metabolism compared to repaglinide in this relatively small sample of type 2 diabetic patients when used as add-on therapy to sulphonylureas and metformin.

Endothelial dysfunction (ED) has been suggested as a possible causal link between postprandial hyperglycemia and cardiovascular events in patients with type 2 diabetes. Recent trials demonstrated a reduction of cardiovascular events by treatment with alpha-glucosidase inhibitor acarbose - a drug which mainly reduces postprandial glucose excursions. We were interested to know whether patients with newly diagnosed type 2 diabetes showed postprandial ED and if so whether acarbose was able to improve this condition. Forearm blood flow (FBF) measurements for assessment of ED were performed in the fasting and postprandial state in 20 newly diagnosed type 2 diabetic patients and 10 healthy control subjects. After baseline examination, patients were randomly assigned to a 20-week treatment of acarbose 100 mg t.i.d or matching placebo, thereafter FBF measurements were repeated. FBF of patients in the fasting state was significantly impaired compared to healthy control subjects (max. FBF 5.3+/-0.7 vs. 8.0+/-0.9 ml/100 ml, p<0.02) and did not change in the postprandial state (max. FBF 5.6+/-0.7 ml/100 ml). In contrast, healthy controls showed a significant improvement of FBF in the postprandial state (11.5+/-1.2 ml/100 ml), which is compatible with postprandial ED in the group of patients. Twenty weeks of acarbose treatment did not affect either fasting or postprandial FBF in patients. Early type 2 diabetes is a state of both fasting and postprandial ED, which is not sensitive to acarbose treatment. Protective cardiovascular effects of acarbose might involve other mechanisms.

So far little is known about how the antidiabetic drugs acting at the level of gastrointestinal mucosa may affect immune and cellular response to food intake. The following study investigated the association between acarbose treatment and postprandial metabolism, immune- and inflammatory activity in patients with early type 2 diabetes: The Acarbose action on low grade Inflammation and Immune response in type 2 Diabetes on Atherosclerosis risk (AIIDA) study. Middle-aged patients (n=87) with early type 2 diabetes (2 h-plasma-glucose >or=11.1 mmol/l and/or HbA1c >or=6.5%) and sub-clinical inflammation (leucocytes >or=6.2 GPt/l and/or hsCRP >or=1.0 mg/l) underwent a mixed meal load (527 kcal). Metabolic parameters and markers of subclinical inflammation were measured at fasting (0'), 2 h-postprandial (2-hpp) and 4-hpp before and after 20 weeks of treatment with acarbose or placebo. Leukocytes and lymphocytes excursion after 20 weeks of treatment was significantly reduced with acarbose 4 h after testmeal [GPt/l] (7.5 vs. 7; p<0.05; and 2.29 vs. 2.14; p<0.05, respectively). Acarbose had only marginal effects on pp glucose, FFA, triglycerides, and insulin excursion. Biomarkers of inflammation (hsCRP, MBL, and PAI1) were not affected by acarbose. Multivariate analysis reveals only baseline leukocytes and of acarbose as independent determinant of 4-h leucocytes excursion. Postprandial metabolic and inflammatory parameters were strongly interrelated. These results suggest pleiotropic effects of acarbose, which may contribute to its vasoprotective potentials.

Diabetes is associated with an increase risk for cardiovascular disease (CVD). Recently, macrovascular complications of diabetes have been shown to start before the development of diabetes. Indeed, several clinical studies have confirmed the increased risk of CVD in patients with impaired glucose tolerance (IGT). Since postprandial hyperglycemia and insulin resistance are thought to play a central role in the development and progression of CVD in patients with IGT, amelioration of postprandial hyperglycemia as well as insulin resistance is a therapeutic target for the prevention of CVD in these high-risk patients. Acarbose, an alpha-glucosidase inhibitor, delays the absorption of carbohydrate from the small intestine, thereby reducing postprandial hyperglycemia. Further, recently, acarbose has been shown to improve insulin resistance in vivo. These findings suggest that acarbose is a promising metabolic modifier that could reduce the risk of CVD in patients with the metabolic syndrome. In this paper, we review the clinical utility of acarbose in various cardiometabolic disorders.

Combinations of insulin and oral antidiabetic drugs (OAD) are often prescribed instead of insulin alone. In this study, the effects of insulin glargine (IG) in combination with repaglinide or acarbose on glycemic parameters were investigated. Obese Type 2 diabetic patients with fasting blood glucose (FBG) levels >or= 7.7 mmol/l [corrected] and hemoglobin glycated (A1C) >or=9% under maximal OAD combination therapy were enrolled. Previous therapies were discontinued, and patients were randomized into 2 groups. The combinations of IG and repaglinide were administered to group 1, and of IG and acarbose to group 2 for 13 weeks. Twenty patients in group 1 and 18 patients in group 2 completed the study. A1C levels were significantly decreased from 10.9+/-1.4% to 7.7+/-1.1% in group 1 and 11.0+/-1.4% to 8.1+/-1.4% in group 2. FBG levels were significantly decreased from 11.9+/-2.7 to 7.1+/-2.3 mmol/l in group 1 and 11.1+/-2.5 to 6.8+/-1.4 mmol/l in group 2. Post-prandial glucose levels were significantly decreased from 15.3+/-3.8 to 10.3+/-3.0 mmol/l in group 1 and 14.0+/-3.1 to 8.9+/-2.2 mmol/l in group 2. Intergroup comparisons indicated no significant differences. More weight gain was detected in group 1, compared to the baseline. Symptomatic hypoglycemia incidence was similar in both groups. Severe hypoglycemic attacks were seen in two patients in group 1. Flatulence incidence was higher in acarbose group. Conclusively, repaglinide and acarbose were equally effective when combined with IG for obese Type 2 diabetic patients controlled inadequately with OAD alone. Furthermore, acarbose seems to have advantages over repaglinide concerning weight gain and severe hypoglycemic attacks.

The STOP-NIDDM trial was an international, double-blind, placebo-controlled randomised study in people with impaired glucose tolerance (IGT). They were treated with an alpha-glucosidase inhibitor, acarbose, to prevent diabetes; the overall number needed to treat (NNT) was 11. In a secondary analysis, we considered the impact of single traits and overall metabolic syndrome (MetS) respectively on risk of diabetes and NNT respectively. In all, there were 1,368 patients. They were followed up for 3.3 years, and the prevalence of MetS was 61%. Multivariate analysis revealed treatment group 2-hour (post-challenge) plasma glucose, glycosylated haemoglobin (HbA1C), triglycerides and leukocyte count as independent predictors. The annual incidence of diabetes in the placebo group with MetS was 18.7% vs. 11.2% in patients without MetS; the corresponding figures in the acarbose group were 13.5% and 9.4%, respectively. The NNT in patients was 5.8 in patients with MetS and 16.5 in those without MetS. In conclusion, most single traits and overall MetS label a very high-risk group in people with IGT. People with MetS reach a NNT to prevent development of new diabetes with acarbose of 5.8.

Postprandial lipemia has emerged as an independent risk factor for coronary artery disease. In this systematic review we examined the effect of the medications used for the management of diabetes, obesity and dyslipidemia on postprandial lipemia. It should be mentioned that no standardization exists for a test meal and for the duration of observation postprandially to allow for direct comparisons between the published studies. Type 2 diabetes mellitus and insulin resistance are associated with enhanced postprandial lipemia. Insulin is effective in reducing both fasting and post prandial total triglyceride levels as well as triglycerides contained in the triglyceride-rich lipoprotein sub-fractions. Additionally, the newer rapid-acting insulin analogues seem to be more effective in the reduction of postprandial lipemia than the short-acting human insulins. Acarbose ameliorates postprandial lipemia and reduces the atherogenic chylomicron and very low density lipoprotein remnants. Metformin reduces both fasting and postprandial triglyceridemia, fasting and post-prandial free fatty acids and may increase the concentrations of the high density lipoprotein cholesterol. Sulfonylureas reduce fasting and postprandial triglyceride levels while data on the effect on high density lipoprotein levels are inconsistent. The effect of meglitinides on postprandial lipid metabolism is neutral. Rosiglitazone decreases fasting and postprandial free fatty acids but has no significant effect on fasting and postprandial triglycerides. Pioglitazone has additional beneficial effects on lipid metabolism because it reduces postprandial free fatty acids, fasting and postprandial triglycerides and increases high density lipoprotein cholesterol levels. Limited available data suggest that glucagon-like peptide-1 analogues and vildagliptin reduce postprandial lipemia through reduction of intestinally-derived triglycerides. No data exist on the effect of sitagliptin on postprandial lipemia. Orlistat improves postprandial lipemia by reducing the absorption of the dietary fat; no data exist on the effect of sibutramine and rimonabant on the metabolism of lipids in the postprandial state.

Background: We hypothesized that acarbose would delay conversion from impaired glucose tolerance (IGT) to type 2 diabetes by alleviating postprandial hyperglycaemia. Our study's main objective was to investigate the effect of acarbose in IGT-persons on their 2-h plasma glucose level and beta-cell function., Subjects and Methods: The study included a random sample of 45-70-year-old residents of Hoorn, Netherlands, with mean fasting plasma glucose < 7.8 mmol/L and mean 2-h plasma glucose of 8.6-11.1 mmol/L (measured by two successive oral glucose tolerance tests). After a qualification period, participants were randomized to acarbose treatment or placebo. Insulin secretion and insulin sensitivity were measured by hyperglycaemic clamp. After a 3-year treatment, analyses were performed of both the intention-to-treat and the per-protocol groups., Results: Of the 12 093 residents who received postal invitations, 118 participants were randomized. The mean difference of the post-load plasma glucose after 3 years, was - 1.16 mmol/L (95% CI: - 2.03; - 0.17). The absolute risk reduction for diabetes was 6% (95% CI: - 9; 21). No effect was seen on insulin secretion and insulin sensitivity., Conclusions: In patients with IGT, treatment with acarbose was associated with beneficial effects on 2-h plasma glucose levels but not with improvement of beta-cell function., (Copyright 2008 John Wiley & Sons, Ltd.)

Background: Postprandial hypotension (PPH) occurs frequently in elderly people and may lead to syncope, falls, dizziness, weakness, angina pectoris, and stroke. Some studies suggest that the magnitude of the postprandial fall in blood pressure (BP) is influenced by the rate at which glucose enters the small intestine. We hypothesized that acarbose (alpha-glucosidase inhibitor), a hypoglycemic agent that decreases the rate of glucose absorption in the small intestine, would attenuate PPH in the elderly, and would be safe in the treatment., Methods: Forty-three elderly in-patients with PPH were recruited. All of them were in relatively stable conditions. They had semi-liquid standard meals without and with acarbose for the two following days: screening day and intervention day. Blood pressure and heart rate (HR) were recorded at baseline and every 15 minutes for 120 minutes using a non-invasive ambulatory blood pressure monitoring system during the study, and ejection fraction (EF) and fractional shortening (FS) were measured by two dimensional echocardiography., Results: Compared with the screening day, the falls in systolic, diastolic and mean arterial blood pressure (SBP, DBP, MAP) (all P < 0.05) were significantly attenuated after taking acarbose during breakfast, so were MAP (P < 0.05) during lunch, DBP (P < 0.05) and MAP (P < 0.05) during supper. The change of HR was not statistically significant after taking acarbose in three meals. EF and FS were positively correlated with the relief rate. The effective power was 63%, and the incidence of adverse drug reaction (ADR) was 9%., Conclusion: Acarbose is effective and safe in the treatment of elderly patients with PPH.

Objective: To determine the clinical, endocrine, and metabolic effects of acarbose use in overweight and nonoverweight patients with polycystic ovarian syndrome (PCOS)., Design: Prospective analysis., Setting: Gynecology and infertility clinic of a tertiary care medical center., Patient(s): Seventy-four patients with PCOS and 30 healthy women., Intervention(s): Acarbose use., Main Outcome Measure(s): Clinical findings of hyperandrogenism, body mass indices, LH, FSH, DHEAS, total T, PRL, basal insulin, fasting glucose/insulin levels, and lipid profiles., Result(s): Acarbose treatment improved LH/FSH levels, decreased total T, DHEAS, basal insulin, low-density lipoprotein, very low-density lipoprotein, and triglyceride levels, and increased high-density lipoprotein levels in patients with PCOS. Basal insulin and fasting glucose/insulin levels reacted more significantly in overweight patients undergoing acarbose treatment., Conclusion(s): Acarbose has been found to improve insulin levels and thus glucose/insulin ratios more effectively in overweight patients compared with nonoverweight patients with PCOS. This drug seems to be an effective drug to be used in overweight as well as nonoverweight patients with PCOS.

Visceral obesity and insulin resistance are regarded as risk factors for atherosclerosis. Epidemiologic studies have demonstrated long-term anti-atherosclerotic effects with administration of alpha-glucosidase inhibitors. Alpha-glucosidase inhibitors also have been reported to enhance glucagon-like peptide 1 (GLP-1) secretion. We compared the postprandial effects of a single administration of miglitol and acarbose on glucose and lipid metabolism, on insulin requirement, on GLP-1 secretion, and on inflammatory and endothelial markers in viscerally obese subjects. Twenty-four viscerally obese subjects with relative insulin resistance participated in this study. Subjects were given a single dose of miglitol (50 mg), acarbose (100 mg), or placebo blindly and randomly before a meal in a crossover design. The meal loads after drug administration were tested 3 times within 2 weeks. We measured glucose, insulin, lipids, lipoprotein lipase, interleukin 6, intracellular adhesion molecule 1, vascular cell adhesion molecule 1, and active GLP-1 at before and various minutes after the meal. Single administration of both alpha-glucosidase inhibitors had several beneficial effects in improving postprandial hyperglycemia and reducing postprandial insulin requirement approximately 25% of placebo without adversely affecting lipid profiles. Although lipoprotein lipase levels within 2 hours after the meal did not show differences among miglitol, acarbose, and placebo administrations, miglitol significantly suppressed the increases in triglycerides, remnant-like particle triglycerides, and remnant-like particle cholesterol compared to acarbose and placebo in the early phase. Miglitol also significantly enhanced active GLP-1 secretion to a greater extent than acarbose (P < .01) and placebo (P < .001), and significantly suppressed the postprandial increase in interleukin 6 compared to placebo (P < .01). The results point to the potential suitability of miglitol as an anti-atherosclerotic effect in viscerally obese subjects, in preference to acarbose. Further studies are needed to elucidate the long-term effects on enhanced GLP-1 secretion and anti-atherosclerosis.

Adiponectin is an anti-diabetic and anti-atherogenic adipokine that serves as a major determinant of insulin sensitivity. Thiazolidine derivatives increase circulating adiponectin, particularly the high molecular weight isoform, which has been shown to well correlate with amelioration of insulin resistance by thiazolidines in diabetic patients. alpha-glucosidase inhibitors are another class of anti-diabetic agents that specifically reduce postprandial blood glucose elevations, but its effect on adiponectin is largely unknown. In the present study we investigated effect of an alpha-glucosidase inhibitor, acarbose, together with pioglitazone, the only thiazolidine derivative available in Japan, on serum concentrations of adiponectin. Seventeen patients with type 2 diabetes were treated with acarbose and sixteen with pioglitazone for three months. Treatment with acarbose and pioglitazone decreased HbA1c values by 0.49% and 0.63%, respectively. Pioglitazone, as expected, increased serum levels of total adiponectin by 2.1 fold and its high molecular weight isoform by 3.6 fold. We found that acarbose also caused a small but significant increase in serum concentrations of total adiponectin. However, in contrast to pioglitazone, no appreciable changes were observed in the levels of high molecular weight adiponectin. In conclusion, acarbose increases serum concentrations of total adiponectin without preference of the high molecular weight isoform in type 2 diabetic patients. Clinical relevance of the increased adiponectin to the acarbose effects remains to be elucidated.

Introduction: Excessive postprandial (pp) glucose excursion in people with IGT and type 2 diabetes is associated with a cascade of proatherogenic events. Acarbose, a potent competitive inhibitor of alpha-glucosidases of the small intestine specifically reduces pp hyperglycemia with an average reduction of HbA1c by 0.8% in Cochrane metaanalysis. This is associated with pleiotropic effects on a broad spectrum of cardiovascular (CV) risk factors: reduction of overweight, lowering of blood pressure, triglycerides, hsCRP, fibrinogen and other biomarkers of low grade inflammation., Results and Discussion: Flow mediated vasodilation was improved and progression of intima media thickness was reduced by acarbose. In the STOP-NIDDM trial in people with IGT acarbose decreased the incidence of diabetes by 36%. The STOP-NIDDM trial with CV events as secondary objective is the only intervention trial in people with IGT so far with a significant benefit for CV disease inclusive hypertension. In a metaanalysis of controlled studies (MeRIA) in patients with type 2 diabetes, treatment with acarbose was associated with a 64% lower rate of myocardial infarction and 35% less CV events., Conclusion: Thus results so far available prove that acarbose is an effective and safe drug to treat abnormal glucose tolerance. They suggest that acarbose can help to control a broad spectrum of CV risk factors and may prevent CV disease.

Objective: To review the evidence for use of acarbose in the management of polycystic ovary syndrome (PCOS)., Data Sources: Relevant publications were identified through a systematic search of PubMed English-language literature (1950-February 2008) using the MeSH terms and key words acarbose and polycystic ovary syndrome., Study Selection and Data Extraction: The literature search retrieved 6 primary literature citations. Three randomized controlled clinical trials and one open-label study were evaluated. The other 2 citations were not evaluated due to only a peripheral mention of PCOS in relation to diabetes., Data Synthesis: PCOS is a complex disorder presenting most commonly with oligomenorrhea or amenorrhea, infertility, hirsutism, acne, and obesity. Acarbose is a promising therapy for PCOS because of its effects on postprandial insulin levels. In multiple clinical studies, acarbose improved hirsutism, acne, and menstrual irregularities through reduction in androgen concentrations and through increased androgen binding. When compared with metformin in women with PCOS and clomiphene-resistant infertility, acarbose induced greater weight loss and improved menstrual regularity and signs of fertility to a similar degree. Markers of cardiovascular risk were also significantly improved following 6 months of acarbose therapy in obese women with PCOS. Adverse effects, specifically gastrointestinal, were documented. Despite promising results, the studies were limited by small sample sizes and, in some cases, methods that were not clearly defined., Conclusions: Several trials have evaluated the use of acarbose in the management of PCOS with positive clinical evidence, but the results of these trials have not been corroborated by more rigorous studies.

Background: Several epidemiological studies have shown that postprandial hyperglycemia is associated with an increased risk of cardiovascular disease (CVD). The present study was conducted in order to compare the effects of acarbose and glimepiride treatment on serum lipoprotein profiles in patients with type 2 diabetes., Methods: A total of 37 patients with newly diagnosed type 2 diabetes were studied. The patients were assigned randomly to treatment for 12 weeks with either acarbose (n=13, 100 mg x 3/day, group A), glimepiride (n=13, 2 mg/day, group G) or diet only (n=11, group D). Lipid and lipoprotein profiles before and after each treatment were evaluated., Results: A significant reduction in the net electronegative charge of low-density lipoprotein (emLDL) was observed in group A (-1.8, P<0.01), whereas no significant change in emLDL was observed in groups G and D. In group A, small VLDL and very small LDL levels were also decreased significantly (P<0.05). The change in emLDL levels correlated significantly with changes in very small LDL (r=0.751, P<0.01) and oxidized LDL levels (r=0.623, P<0.05)., Conclusion: These results suggest that measurement of serum emLDL may be a sensitive and clinically useful marker for determining qualitative lipoprotein abnormalities in diabetes, and that acarbose treatment lowers CVD risk by decreasing production of emLDL.

1. Inhibitors of intestinal glucosidases have been shown to improve glycaemic control in diabetic and obese humans and animals. In the present study, we have investigated the effect of 3 months treatment with acarbose on adiposity, food intake and the modulation of hypothalamic neuropeptide Y (NPY) in obese diabetic Wistar (WDF) rats and the possible correlation between changes in overall insulin sensitivity and the level of circulating adipokines, leptin and adiponectin. In addition, we investigated the effect of acarbose on adipocyte insulin signalling. 2. Mature male WDF rats were randomly distributed to one of three treatment groups (no acarbose or 20 or 40 mg of acarbose/100 g diet). After 3 months, blood glucose, cholesterol, triglyceride, insulin, leptin and adiponectin were analysed. Insulin signalling was determined in isolated adipocytes as the stimulation of mitogen-activated protein kinase (MAPK) and Akt phosphorylation; the level of hypothalamic NPY was assessed by immunohistochemistry. 3. Acarbose-treated rats had lower levels of blood glucose, cholesterol, triglyceride, insulin and leptin and an increase in adiponectin compared with untreated animals. There were no changes in bodyweight and adiposity. Stimulation of adipocyte MAPK activity by insulin was higher in rats treated with both doses of acarbose, whereas higher stimulation of Akt phosphorylation was observed with the highest dose of acarbose. Although food intake was not significantly reduced in rats treated with acarbose, the acarbose-treated rats had lower NPY expression in the arcuate nucleus. 4. We conclude that the improvement in overall insulin sensitivity in WDF rats after prolonged acarbose treatment is paralleled by increases in circulating adiponectin and adipocyte insulin responsiveness. Acarbose neither decreases food intake nor reverts obesity, but decreases leptin levels and the expression of the orexigenic NPY in the hypothalamus.

Since Diabetes Control and Complications Trial (DCCT), intensive therapy has been directed at achieving glucose and glycosylated hemoglobin (HbA1c) values as close to normal as possible regarding safety issues. However, hyperglycemia (especially postprandial hyperglycemia) and hypoglicemia continue to be problematic in the management of type 1 diabetes. The objective of associating other drugs to insulin therapy is to achieve better metabolic control lowering postprandial blood glucose levels. Adjunctive therapies can be divided in four categories based on their mechanism of action: enhancement of insulin action (e.g. the biguanides and thiazolidinediones), alteration of gastrointestinal nutrient delivery (e.g. acarbose and amylin) and other targets of action (e.g. pirenzepine, insulin-like growth factor I and glucagon-like peptide-1). Many of these agents have been found to be effective in short-term studies with decreases in HbA1c of 0.5-1%, lowering postprandial blood glucose levels and decreasing daily insulin doses.

Acarbose is an alpha-glucosidase inhibitor acting specifically at the level of postprandial glucose excursion. This compound lowers HbA(1c) by 0.5-1% in patients with Type 2 diabetes, either drug naive or in combination with other antidiabetic drugs. In those with impaired glucose tolerance (IGT), it reduces the incidence of newly diagnosed diabetes by 36.4%. Furthermore, it has beneficial effects on overweight, reduces blood pressure and triglycerides, and downregulates biomarkers of low-grade inflammation. In the Study To Prevent Non-Insulin-Dependent-Diabetes-Mellitus (STOP-NIDDM) trial, acarbose significantly reduced the progression of intima media thickness, incidence of cardiovascular events and of newly diagnosed hypertension. In a meta-analysis of patients with Type 2 diabetes (MERIA), acarbose intake was associated with a reduction of cardiovascular events by 35%. Acarbose is a very safe drug but in approximately 30% of patients, it can cause gastrointestinal complaints due to its mode of action, which in the majority disappear after 1-2 months. Acarbose is approved for treatment of IGT in 25 countries. It can be given alone or in combination with other oral antidiabetics and insulin. Acarbose is particularly effective in those with IGT and early diabetes and patients with comorbidities of the metabolic syndrome.

Overt type 2 diabetes is usually preceded by a condition known as prediabetes, which is characterized by impaired fasting glucose (IFG) and impaired glucose tolerance (IGT). Both IFG and IGT exhibit elevated glucose levels that are not sufficient to be classified as diabetes but that represent the development of insulin resistance. Achieving glycemic control in patients with prediabetes through lifestyle and pharmacologic interventions can effectively prevent or delay the development of diabetes and its associated complications. The first step, however, is to identify patients at risk. Although patients can be identified with an oral glucose tolerance test (OGTT) or a fasting plasma glucose (FPG) screening, a normal FPG does not preclude an elevated OGTT and, therefore, the presence of prediabetes. For patients who progress to type 2 diabetes, intensive therapy aimed at reducing and maintaining glycosylated hemoglobin (A1C) levels < 7% has been shown to reduce the risk of complications. An A1C level > or = 7% should signal the need to initiate or change therapy to achieve glycemic goals.

The aim of this study was to compare the efficacy of treatment with insulin alone, insulin plus acarbose, insulin plus metformin, or insulin plus rosiglitazone in type 2 diabetic subjects who were previously on insulin monotherapy, and to evaluate the effects of these treatments on cardiovascular risk factors including lipid profile, C-reactive protein (CRP) and fibrinogen. Sixty-six poorly controlled type 2 diabetic patients on insulin monotherapy were involved. They were randomized to insulin alone, insulin plus acarbose, insulin plus metformin, or insulin plus rosiglitazone groups for 6 months period. Mean fasting and postprandial glucose values as well as HbA1c levels significantly decreased in all groups. The greatest improvement in HbA1c was observed in insulin plus rosiglitazone (2.4%) and in insulin plus metformin (2%) groups. Daily total insulin dose was increased to 12.7 units/day in insulin alone group, decreased to 4.7 units/day in insulin plus rosiglitazone group, to 4.2 units/day in insulin plus metformin group, and to 2.7 units/day in insulin plus acarbose group. Least weight gain occurred in insulin plus metformin group (1.4 kg) and greatest weight gain occurred in insulin plus rosiglitazone group (4.6 kg). No significant change in lipid levels--except serum triglycerides--was observed in any groups. CRP and fibrinogen levels decreased in all groups, but the decrease in fibrinogen level was significantly greater in insulin plus rosiglitazone group. All groups were comparable in hypoglycemic episodes. No serious adverse event was noted in any group.

Aim: This study was designed to investigate the effect of acarbose in patients with type 2 diabetes with newly initiated insulin treatment who had previously been insufficiently controlled with oral antihyperglycaemic agents [haemoglobin A(1c) (HbA(1c)) >/= 8%]., Methods: In this 20-week double-blind, placebo-controlled study, 163 patients were randomized to receive acarbose up to 100 mg three times a day or matching placebo. Both the groups were newly initiated with insulin, which was adjusted according to blood glucose values. Primary efficacy parameter was the change in HbA(1c) from baseline; changes in daily insulin doses were also assessed., Results: Mean HbA(1c) was significantly reduced by acarbose compared with placebo (2.31 vs. 1.81%, p = 0.033). Insulin doses were comparable at the end of the study. There was no difference in blood glucose and triglyceride levels between the treatment groups. Postprandial serum insulin levels increased in both treatment arms owing to insulin administration but less so under acarbose. In contrast to the placebo group, an increase in body mass index was prevented for acarbose-treated patients., Conclusion: As adjunct administration to newly initiated insulin therapy, acarbose enhances the optimization of blood glucose control in patients with type 2 diabetes.

Objective: To assess the efficacy, tolerability, and safety of the domestic Acarbose capsule (DAC, produced by Luzhou Baoguang Pharmaceutical Co. LTD) in treating patients with type 2 diabetes mellitus., Methods: One hundred and seventy nine type 2 diabetic patients were randomly divided into DAC (group A, 89 patients) and Glucoby (group B, 90 patients) treatment groups. The trial consisted of a 2-4 weeks equilibrated period followed by an 8 week course of treatments. All of the patients were followed up at the 4th week and 8th week after the commencement of the treatments. One hundred and sixty five patients completed the trial, with 81 in group A and 84 in group B., Results: At the 4th week of the treatments, an average reduction of 1.81 and 2.08 mmol/L of fasting blood glucose (FBG) was found in group A and group B, respectively (P > 0.05); and an average reduction of 5.43 and 5.09 mmol/ L of postprandial blood glucose (PBG) was found in group A and group B, respectively (P > 0.05). At the 8th week, an average reduction of 2.35 and 2.62 mmol/L FBG was found in group A and group B, respectively (P > 0.05); and an average of reduction of 5.93 and 5.98 mmol/L of PBG was found in group A and group B, respectively (P > 0.05); The mean HbA(1c) was lowered by 1.07% and 1.20% by DAC and Glucoby respectively (P > 0.05). The incidence rate of side effects in group A was 32.53%, less than that in group B (48.81%). Flatulence was the most common side effect. The clinical effects of both Glucoby and DAC were more significant at the 8th week than at the 4th week., Conclusion: DAC is as effective and safe as Glucobay for treating type 2 diabetic patients.