ao-128 and Diabetes-Mellitus--Type-2

Topics: 1-Deoxynojirimycin; Acarbose; Aged; Blood Glucose; Cardiovascular Diseases; Diabetes Mellitus, Type 2; Glycoside Hydrolase Inhibitors; Humans; Hyperglycemia; Hypoglycemic Agents; Inositol; Metformin; Prediabetic State

Alpha-glucosidase inhibitors (AGI) reduce blood glucose levels and may thus prevent or delay type 2 diabetes mellitus (T2DM) and its associated complications in people at risk of developing of T2DM.. To assess the effects of AGI in people with impaired glucose tolerance (IGT), impaired fasting blood glucose (IFG), moderately elevated glycosylated haemoglobin A1c (HbA1c) or any combination of these.. We searched CENTRAL, MEDLINE, Embase, ClinicalTrials.gov, the World Health Organization International Clinical Trials Registry Platform, and the reference lists of systematic reviews, articles and health technology assessment reports. The date of the last search of all databases was December 2017.. We included randomised controlled trials (RCTs), with a duration of one year or more, comparing AGI with any pharmacological glucose-lowering intervention, behaviour-changing intervention, placebo or no intervention in people with IFG, IGT, moderately elevated HbA1c or combinations of these.. Two review authors read all abstracts and full-text articles or records, assessed quality and extracted outcome data independently. One review author extracted data, which were checked by a second review author. We resolved discrepancies by consensus or involvement of a third review author. For meta-analyses we used a random-effects model with assessment of risk ratios (RRs) for dichotomous outcomes and mean differences (MDs) for continuous outcomes, using 95% confidence intervals (CIs) for effect estimates. We assessed the overall quality of the evidence by using the GRADE instrument.. For this update of the Cochrane Review (first published 2006, Issue 4) we included 10 RCTs (11,814 participants), eight investigating acarbose and two investigating voglibose, that included people with IGT or people "at increased risk for diabetes". The trial duration ranged from one to six years. Most trials compared AGI with placebo (N = 4) or no intervention (N = 4).Acarbose reduced the incidence of T2DM compared to placebo: 670 out of 4014 people (16.7%) in the acarbose groups developed T2DM, compared to 812 out of 3994 people (20.3%) in the placebo groups (RR 0.82, 95% CI 0.75 to 0.89; P < 0.0001; 3 trials; 8008 participants; moderate-certainty evidence). One trial including participants with coronary heart disease and IGT contributed 64% of cases for this outcome. Acarbose reduced the risk of T2DM compared to no intervention: 7 out 75 people (9.3%) in the acarbose groups developed T2DM, compared to 18 out of 65 people (27.7%) in the no-intervention groups (RR 0.31, 95% CI 0.14 to 0.69; P = 0.004; 2 trials; 140 participants; very low-certainty evidence).Acarbose compared to placebo did not reduce or increase the risk of all-cause mortality (RR 0.98, 95% CI 0.82 to 1.18; P = 0.86; 3 trials; 8069 participants; very low-certainty evidence), cardiovascular mortality (RR 0.88; 95% CI 0.71 to 1.10; P = 0.26; 3 trials; 8069 participants; very low-certainty evidence), serious adverse events (RR 1.12, 95% CI 0.97 to 1.29; P = 0.13; 2 trials; 6625 participants; low-certainty evidence), non-fatal stroke (RR 0.50, 95% CI 0.09 to 2.74; P = 0.43; 1 trial; 1368 participants; very low-certainty evidence) or congestive heart failure (RR of 0.87; 95% CI 0.63 to 1.12; P = 0.40; 2 trials; 7890 participants; low-certainty evidence). Acarbose compared to placebo reduced non-fatal myocardial infarction: one out of 742 participants (0.1%) in the acarbose groups had a non-fatal myocardial infarction compared to 15 out of 744 participants (2%) in the placebo groups (RR 0.10, 95% CI 0.02 to 0.53; P = 0.007; 2 trials; 1486 participants; very low-certainty evidence). Acarbose treatment showed an increased risk of non-serious adverse events (mainly gastro-intestinal events), compared to placebo: 751 of 775 people (96.9%) in the acarbose groups experienced an event, compared to 723 of 775 people (93.3%) in the placebo groups (RR 1.04; 95% CI 1.01 to 1.06; P = 0.0008; 2 trials; 1550 participants). Acarbose compared to no intervention showed no advantage or disadvantage for any of t. AGI may prevent or delay the development of T2DM in people with IGT. There is no firm evidence that AGI have a beneficial effect on cardiovascular mortality or cardiovascular events.

Topics: Acarbose; Blood Glucose; Cause of Death; Diabetes Mellitus, Type 2; Diet; Exercise; Fasting; Glucose Intolerance; Glycoside Hydrolase Inhibitors; Humans; Incidence; Inositol; Metformin; Prediabetic State; Randomized Controlled Trials as Topic

Type 2 diabetes mellitus (T2DM) is currently at epidemic proportions and the forecast is for a continued sharp increase in global prevalence. An even larger proportion of the population has prediabetes (impaired glucose tolerance [IGT]) underscoring the urgent need for preventive strategies. Even in the presence of adequate glycosylated hemoglobin (HbA1c) levels, postprandial hyperglycemia can occur and is known to have a stronger association with cardiovascular morbidity than fasting glucose. The α-glucosidase inhibitor voglibose is widely used in Japan to improve postprandial hyperglycemia.. This review examines the literature for the pharmacology, pharmacokinetics, clinical efficacy and safety of voglibose in patients with T2DM. Particular focus is on its efficacy in preventing T2DM in individuals with IGT and its efficacy as add-on therapy or in combination with other oral antidiabetic agents in patients with T2DM.. As the relationship between glucose levels and cardiovascular risk extends below the diabetic threshold, postprandial hyperglycemia is recognized as a key therapeutic target in the treatment of T2DM. Strategies to prevent the progression of IGT to overt T2DM have enormous potential to reduce the individual and societal burden of disease. Voglibose is the first oral antidiabetic agent to gain approval in Japan for this indication.

Topics: Atherosclerosis; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Drug Therapy, Combination; Glucose Intolerance; Humans; Hypoglycemic Agents; Inositol; Insulin; Practice Guidelines as Topic; Treatment Outcome

Population explosion, urbanization, changes in lifestyle management, improper food habits and various other factors play focal contributors in the massive prevalence of type 2 diabetes mellitus in the developing countries. Although insulin is the cornerstone in the management of type 1 diabetes; insulin, anti-hyperglycemic and hypoglycemic agents are proved to be effective in type 2 diabetes, although their efficacy decreases with the progress of the disease. Moreover a significant number of side effects, mostly hypoglycemia and weight gain have put a bar in using these drugs confidently. Many novel therapeutic strategies with convincing efficacy and less adverse effects are currently emerging for providing efficient means of treatment of this disorder. This article mainly focuses on newer and unconventional pharmaceutical or biotechnical strategies that may or may not have been implied for the treatment of Type 2 Diabetes mellitus on a widescale basis so far. These strategies are supposed to be efficient in controlling glycemic levels and possess a significant potential to reduce the co-morbidities associated with this disease.

Topics: Benzhydryl Compounds; Developing Countries; Diabetes Mellitus, Type 2; Drug Therapy, Combination; Feeding Behavior; Glucosides; Health Knowledge, Attitudes, Practice; Humans; Hypoglycemic Agents; Inositol; Isoindoles; Nanotechnology; Prevalence; Risk Reduction Behavior; Stem Cell Transplantation; Urbanization

Topics: Animals; Carbohydrate Metabolism; Diabetes Mellitus, Type 2; Enzyme Inhibitors; Glucose Intolerance; Glycoside Hydrolase Inhibitors; Humans; Hyperglycemia; Hypoglycemic Agents; Inositol; Insulin; Insulin Secretion; Intestinal Absorption; Male; Middle Aged; Randomized Controlled Trials as Topic

Alpha-glucosidase inhibitors such as acarbose or miglitol, have the potential to improve glycemic control in type 2 diabetes mellitus. The true value of these agents, especially in relation to diabetes related mortality and morbidity, has never been investigated in a systematic literature review and meta-analysis.. To assess the effects of alpha-glucosidase inhibitors s in patients with type 2 diabetes mellitus.. We searched The Cochrane Library, MEDLINE, EMBASE, Current Contents, LILACS, databases of ongoing trials, reference lists of reviews on the topic of alpha-glucosidase inhibitors and we contacted experts and manufacturers for additional trials. Date of most recent search: December 2003 (Current Contents) and April 2003 (other databases).. Randomised controlled trials of at least 12 weeks duration comparing alpha-glucosidase inhibitor monotherapy in patients with type 2 diabetes with any other intervention and that included at least one of the following outcomes: mortality, morbidity, quality of life, glycemic control, lipids, insulin levels, body weight, adverse events.. Two reviewers read all abstracts, assessed quality and extracted data independently. Discrepancies were resolved by consensus or by the judgement of a third reviewer. A statistician checked all extracted data entrance in the database. We attempted to contact all authors for data clarification.. We included 41 trials (8130 participants), 30 investigated acarbose, seven miglitol, one trial voglibose and three trials compared different alpha-glucosidase inhibitors. Study duration was 24 weeks in most cases and only two studies lasted amply longer than one year. We found only few data on mortality, morbidity and quality of life. Acarbose had a clear effect on glycemic control compared to placebo: glycated haemoglobin -0.8% (95% confidence interval -0.9 to -0.7), fasting blood glucose -1.1 mmol/L (95% confidence interval -1.4 to -0.9), post-load blood glucose -2.3 mmol/L (95% confidence interval -2.7 to -1.9). The effect on glycated haemoglobin by acarbose was not dose-dependent. We found a decreasing effect on post-load insulin and no clinically relevant effects on lipids or body weight. Adverse effects were mostly of gastro-intestinal origin and dose dependent. Compared to sulphonylurea, acarbose decreased fasting and post-load insulin levels by -24.8 pmol/L (95% confidence interval -43.3 to -6.3) and -133.2 pmol/L (95% confidence interval -184.5 to -81.8) respectively and acarbose caused more adverse effects.. It remains unclear whether alpha-glucosidase inhibitors influence mortality or morbidity in patients with type 2 diabetes. Conversely, they have a significant effect on glycemic control and insulin levels, but no statistically significant effect on lipids and body weight. These effects are less sure when alpha-glucosidase inhibitors are used for a longer duration. Acarbose dosages higher than 50 mg TID offer no additional effect on glycated hemoglobin but more adverse effects instead. Compared to sulphonylurea, alpha-glucosidase inhibitors lower fasting and post-load insulin levels and have an inferior profile regarding glycemic control and adverse effects.

Topics: 1-Deoxynojirimycin; Acarbose; Diabetes Mellitus, Type 2; Enzyme Inhibitors; Glucosamine; Glycoside Hydrolase Inhibitors; Humans; Hypoglycemic Agents; Imino Pyranoses; Inositol; Randomized Controlled Trials as Topic

Type 2 diabetes mellitus is a major health problem associated with excess morbidity and mortality. As the prevalence of this metabolic disorder is rapidly increasing and current treatment fails to stabilise the disease in most patients, prevention should be considered as a key objective in the near future. People who develop type 2 diabetes pass through a phase of impaired glucose tolerance (IGT). Defects in the action and/or secretion of insulin are the two major abnormalities leading to development of glucose intolerance. Any intervention in the impaired glucose tolerance phase that reduces resistance to insulin or protects the beta-cells, or both, should prevent or delay progression to diabetes.Acarbose, miglitol and voglibose act by competitively inhibiting the alpha-glucosidases, a group of key intestinal enzymes involved in the digestion of carbohydrates. They decrease both postprandial hyperglycaemia and hyperinsulinaemia, and thereby may improve sensitivity to insulin and release the stress on beta-cells. These compounds do not induce hypoglycaemia and have a good safety profile, although gastrointestinal adverse effects may limit long-term compliance to therapy. The recent placebo-controlled prospective STOP-noninsulin-dependent diabetes mellitus (STOP-NIDDM) trial demonstrated that acarbose 100mg three times daily reduces the risk of developing type 2 diabetes in patients with IGT (relative risk reduction of 25% after a mean follow-up of 3.3 years). The 6-year Early Diabetes Intervention Trial (EDIT), comparing the effect of acarbose 50mg three times daily to that of metformin, showed a trend to a positive effect of acarbose compared with placebo, in a mid-term 3-year analysis, which should be confirmed in the final analysis. To our knowledge, no such prevention intervention trials have been or are currently being performed with miglitol or voglibose. In conclusion, because of its absence of toxicity and its particular mechanism of action on gastrointestinal tract and indirect consequences on both insulin action and beta-cell function, acarbose may be used to prevent type 2 diabetes. If the ongoing EDIT trial confirms the positive results of the recent STOP-NIDDM trial, acarbose could be used, either as an alternative or in addition to changes in lifestyle, to delay development of diabetes in patients with IGT. However, the best dosage of acarbose for this specific indication remains to be specified, especially when all three important parameter

Topics: 1-Deoxynojirimycin; Acarbose; Diabetes Mellitus, Type 2; Enzyme Inhibitors; Glucosamine; Glycoside Hydrolase Inhibitors; Humans; Hypoglycemic Agents; Imino Pyranoses; Inositol; Randomized Controlled Trials as Topic

Several epidemiological studies have shown an association between postprandial hyperglycemia and mortality from cardiovascular disease. Postprandial hyperglycemia is frequently associated with visceral obesity which plays a key role in metabolic abnormalities such as dyslipidemia and hypertension. Inhibitors of alpha-glucosidase and nateglinide have beneficial effects on the metabolic syndrome associated with visceral obesity. Voglibose in combination with diet therapy reduces visceral fat deposition and ameliorates insulin resistance. Acarbose slightly reduces blood pressure of hypertensive diabetic patients. Nateglinide, a rapidly acting insulin secretagogue, lowers postprandial glucose levels without significant body weight gain. These drugs may protect pancreatic beta-cells from postprandial glucose toxicity and prevent the progression of diabetes.

Topics: Acarbose; Cyclohexanes; Diabetes Complications; Diabetes Mellitus; Diabetes Mellitus, Type 2; Enzyme Inhibitors; Glycoside Hydrolase Inhibitors; Humans; Hyperglycemia; Hypertension; Hypoglycemic Agents; Inositol; Insulin Resistance; Nateglinide; Obesity; Phenylalanine; Postprandial Period

Topics: Acarbose; Animals; Diabetes Mellitus, Type 2; Enzyme Inhibitors; Glycoside Hydrolase Inhibitors; Humans; Hyperglycemia; Hyperinsulinism; Hyperlipidemias; Hypoglycemic Agents; Inositol; Obesity; Postprandial Period

Topics: Acarbose; Chemical and Drug Induced Liver Injury; Contraindications; Diabetes Mellitus, Type 2; Drug Therapy, Combination; Dyspepsia; Enzyme Inhibitors; Glycoside Hydrolase Inhibitors; Humans; Hyperammonemia; Hypoglycemia; Hypoglycemic Agents; Inositol; Patient Selection

Topics: Acarbose; Clinical Trials as Topic; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Drug Therapy, Combination; Glycoside Hydrolase Inhibitors; Humans; Hyperglycemia; Hypoglycemic Agents; Inositol; Insulin; Postprandial Period

Topics: Carbohydrate Metabolism; Diabetes Mellitus, Type 2; Drug Therapy, Combination; Enzyme Inhibitors; Glycoside Hydrolase Inhibitors; Humans; Hypoglycemic Agents; Inositol; Insulin; Insulin Resistance; Insulin Secretion; Sulfonylurea Compounds

Topics: Acarbose; Animals; Biguanides; Chromans; Clinical Trials as Topic; Diabetes Mellitus, Type 2; Drug Therapy, Combination; Enzyme Inhibitors; Glycoside Hydrolase Inhibitors; Humans; Hypoglycemic Agents; Inositol; Insulin Resistance; Pioglitazone; Sulfonylurea Compounds; Thiazoles; Thiazolidinediones; Troglitazone

Topics: Blood Glucose; Diabetes Mellitus, Type 2; Drug Therapy, Combination; Glycated Hemoglobin; Glycoside Hydrolase Inhibitors; Humans; Hypoglycemic Agents; Inositol; Protein Precursors; Sulfonylurea Compounds

Topics: Acarbose; Animals; Chromans; Diabetes Mellitus, Type 2; Drug Therapy, Combination; Glycoside Hydrolase Inhibitors; Humans; Hypoglycemic Agents; Inositol; Insulin Resistance; Pioglitazone; Thiazoles; Thiazolidinediones; Trisaccharides; Troglitazone

Topics: Acarbose; Diabetes Mellitus, Type 2; Diet, Diabetic; Exercise Therapy; Humans; Hyperglycemia; Hypoglycemic Agents; Inositol; Insulin; Insulin Resistance; Postprandial Period; Sulfonylurea Compounds; Trisaccharides

To elucidate the long-term cardiovascular benefit of lowering postprandial hyperglycemia (PPG) in early-stage T2DM patients.. This 10-year post-trial follow-up study included 243 patients from the DIANA (DIAbetes and diffuse coronary Narrowing) study, a multi-center randomized controlled trial which compared the efficacy of one-year life-style and pharmacological (voglibose/nateglinide) intervention lowering PPG on coronary atherosclerosis in 302 early-stage T2DM subjects [impaired glucose tolerance (IGT) or newly-diagnosed T2DM] (UMIN-CTRID#0000107). MACE (all-cause death, non-fatal MI or unplanned coronary revascularization) were compared in (1) three assigned therapies (life-style intervention/vogliose/nateglinide) and (2) patients with and without improvement of PPG (reversion from IGT to NGT or from DM to IGT/NGT on 75 g oral glucose tolerance test).. During the 10-year post-trial observational period, voglibose (HR = 1.07, 95%CI: 0.69-1.66, p = 0.74) or nateglinide (HR = 0.99, 95%CI: 0.64-1.55, p = 0.99) did not reduce MACE. Similarly, achieving the improvement of PPG was not associated with a reduction of MACE (HR = 0.78, 95%CI: 0.51-1.18, p = 0.25). However, in IGT subjects (n = 143), this glycemic management significantly reduced the occurrence of MACE (HR = 0.44, 95%CI: 0.23-0.86, p = 0.01), especially unplanned coronary revascularization (HR = 0.46, 95%CI: 0.22-0.94, p = 0.03).. The early improvement of PPG significantly reduced MACE and unplanned coronary revascularization in IGT subjects during the post-trial 10-year period.

Topics: Blood Glucose; Coronary Artery Disease; Diabetes Mellitus, Type 2; Follow-Up Studies; Glucose Intolerance; Humans; Nateglinide

Sodium-glucose cotransporter 2 inhibitors could reduce cardiovascular events in patients with heart failure irrespective of diabetes status. In this prespecified sub-analysis of randomised-controlled trial, we investigated the efficacy of luseogliflozin (2.5 mg daily), a sodium-glucose cotransporter 2 inhibitor, with that of voglibose (0.6 mg daily), an alpha-glucosidase inhibitor, on high-risk lipid profile and inflammatory markers in patients with type-2 diabetes and heart failure. Among the 157 patients studied, there were no significant differences in the mean malondialdehyde LDL or small-dense LDL cholesterol levels between the luseogliflozin and voglibose groups (percent change: 0.2% vs. - 0.6%, p = 0.93; - 1.7% vs. - 8.6%, p = 0.21) after 12 weeks in comparison to levels at the baseline. No significant difference was observed between the two groups in the adiponectin and high-sensitivity C-reactive protein levels after 12 weeks compared to the baseline levels (percent change, - 1.6% vs. - 4.0% and 22.5% vs. 10.0%; p = 0.52 and p = 0.55, respectively). In conclusion, in patients with type-2 diabetes and heart failure, compared to voglibose, luseogliflozin did not significantly improve the high-risk lipoprotein profile including malondialdehyde LDL and small-dense LDL cholesterol or the levels of inflammatory markers, including adiponectin and high-sensitivity C-reactive protein.Trial registration: Trial number: UMIN-CTR, UMIN000018395; Registered 23 July 2015; URL: https://www.umin.ac.jp/ctr/index.htm .

Topics: Adiponectin; Biomarkers; C-Reactive Protein; Cholesterol, LDL; Diabetes Mellitus, Type 2; Glucose; Heart Failure; Humans; Inositol; Malondialdehyde; Sodium; Sorbitol

Glycemic variability is a risk factor for total death and cardiovascular events. There are no obvious guidelines for the direct treatment of glycemic variability, but it can be improved with the treatment of postprandial hyperglycemia.. We compared the effect of repaglinide versus the combination of mitiglinide and voglibose, used to improve postprandial hyperglycemia, on glycemic variability in Japanese patients with type 2 diabetes.. We performed an open-label randomized cross-over trial between April 2016 and April 2018. Patients with type 2 diabetes who were admitted to our hospital were enrolled in our study (n = 12). Glycemic variability. was assessed using a continuous glucose monitoring system.. The average glucose level of the repaglinide phase (146.1 ± 20.7 mg/dl) and the combination of mitiglinide and voglibose phase (132.3 ± 19.8 mg/dl) were similar (P = 0.10). The standard division (P = 0.0005), coefficient of variation (P = 0.006), and mean amplitude of glycemic excursion (P = 0.002) of glucose were lower in the combination of mitiglinide and voglibose phase than in the repaglinide phase.. Treatment with the combination of mitiglinide and voglibose might be more effective than repaglinide for the improvement of glycemic variability.

Topics: Blood Glucose; Blood Glucose Self-Monitoring; Carbamates; Cross-Over Studies; Diabetes Mellitus, Type 2; Humans; Hypoglycemic Agents; Inositol; Isoindoles; Japan; Piperidines

Topics: Aged; Biomarkers; Diabetes Mellitus, Type 2; Drug Administration Schedule; Female; Heart Failure; Humans; Hypoglycemic Agents; Inositol; Male; Middle Aged; Natriuretic Peptide, Brain; Prospective Studies; Sodium-Glucose Transporter 2 Inhibitors; Sorbitol; Stroke Volume

Combination of metformin to reduce the fasting plasma glucose level and an α-glucosidase inhibitor to decrease the postprandial glucose level is expected to generate a complementary effect. We compared the efficacy and safety of a fixed-dose combination of voglibose plus metformin (vogmet) with metformin monotherapy in drug-naïve newly-diagnosed type 2 diabetes mellitus.. A total of 187 eligible patients aged 20 to 70 years, with a glycosylated hemoglobin (HbA1c) level of 7.0% to 11.0%, were randomized into either vogmet or metformin treatments for 24 weeks. A change in the HbA1c level from baseline was measured at week 24.. Vogmet is a safe antihyperglycemic agent that controls blood glucose level effectively, yields weight loss, and is superior to metformin in terms of various key glycemic parameters without increasing the risk of hypoglycemia.

Topics: Adult; Aged; Blood Glucose; Diabetes Mellitus, Type 2; Double-Blind Method; Drug Therapy, Combination; Female; Glycemic Index; Humans; Hypoglycemic Agents; Inositol; Male; Metformin; Middle Aged; Postprandial Period; Treatment Outcome; Young Adult

To assess the efficacy and safety of sitagliptin compared with voglibose added to combined metformin and insulin in patients with newly diagnosed type 2 diabetes (T2DM).. In this 12-week prospective, randomized, parallel trial, 70 newly diagnosed T2DM patients with glycosylated hemoglobin (HbA1c) ≥9% and/or fasting plasma glucose (FPG) ≥11.1 mmol/L were randomized (1:1) to receive sitagliptin 100 mg per day + metformin + insulin glargine or voglibose 0.2 mg three times daily + metformin + insulin glargine. Change in HbA1c at week 12 was the primary endpoint.. The mean baseline HbA1c was 11.0% in the patients. The changes in HbA1c from baseline were -6.00% in the sitagliptin group and -3.58% in the voglibose group, and the between-group difference was -2.42% (95% CI -1.91 to -2.93, p=0.02). The differences in FPG and homeostatic model assessment of β-cell function (HOMA-β) and the change in body weight between groups from baseline were -2.95 mmol/L (p=0.04), 43.91 (p=0.01) and -2.23 kg (p=0.01), respectively. One patient (2.9%) in the sitagliptin group and three patients (8.6%) in the voglibose group exhibited hypoglycemia.. Sitagliptin added to combined metformin and insulin therapy showed greater efficacy and good safety regarding hypoglycemia in patients with newly diagnosed T2DM compared with voglibose.

Topics: Adult; Aged; Diabetes Mellitus, Type 2; Female; Humans; Hypoglycemic Agents; Inositol; Male; Metformin; Middle Aged; Prospective Studies; Sitagliptin Phosphate; Treatment Outcome

Recently, we reported that linagliptin had equivalent efficacy to voglibose in reducing postprandial blood glucose levels in drug-naïve patients with type 2 diabetes (L-STEP Study). As a sub-study of the L-STEP Study we examined the effect of linagliptin on postprandial lipids profile. Between October 2012 and April 2014, the study enrolled patients with type 2 diabetes mellitus who had inadequate glycemic control. Patients were randomly assigned to either the linagliptin group (5 mg once daily, n = 85) or the voglibose group (0.2 mg/meal thrice daily, n = 71). Meal tolerance tests were performed at baseline (week 0) and endpoint (week 12). The increments in 4-h postprandial triglyceride, remnant lipoprotein cholesterol (RLP-C), and apolipoprotein B48 (ApoB48) from baseline to endpoint in the linagliptin group were lower (p < 0.001, p = 0.025 and p < 0.001). 4-h postprandial ApoB48 at endpoint was lower in the linagliptin group (p = 0.007), and positive correlation was detected between change of ApoB48 and changes in both triglyceride (r = 0.67, p < 0.001) and RLP-C (r = 0.73, p < 0.001) at 4 h. This study revealed that in drug-naïve Japanese patients with relatively mild type 2 diabetes mellitus, linagliptin improves not only postprandial blood glucose level but also levels of lipids such as TG and RLP-C by reducing the ApoB48 level compared with voglibose.

Topics: Aged; Blood Glucose; Diabetes Mellitus, Type 2; Dipeptidyl-Peptidase IV Inhibitors; Female; Humans; Hypoglycemic Agents; Inositol; Linagliptin; Lipids; Male; Middle Aged; Postprandial Period; Treatment Outcome

Glucose excursions and hypoglycemia are associated with cardiovascular complications. However, no studies have evaluated glucose excursions and the frequency of hypoglycemia in patients treated with mitiglinide/voglibose versus glimepiride as add-on to dipeptidyl peptidase-4 inhibitor therapy.. This cross-over trial included 20 patients with type 2 diabetes. After initiating vildagliptin 100 mg, patients were randomly assigned to receive mitiglinide 10 mg/voglibose 0.2 mg three times daily for 3 days followed by glimepiride 1 mg once daily for the subsequent 3 days as add-on therapy, or vice versa. Glucose excursions and hypoglycemia frequency were measured using 24-h continuous glucose monitoring. Metabolic profile changes were evaluated using a meal tolerance test.. The mean glucose levels in the mitiglinide/voglibose and glimepiride phases were identical (8.01 vs 8.24 mmol/L, respectively). However, during the mitiglinide/voglibose phase compared with the glimepiride phase, the standard deviation of glucose (1.30 vs 2.10 mmol/L; P < 0.001), mean amplitude of glycemic excursions (3.47 vs 5.28 mmol/L; P < 0.001), M-value (24.6 vs 70.0; P < 0.001), continuous overlapping net glycemic action for a 1-h time interval (22.6 vs 31.0; P < 0.001), and area under the curve >10 mmol/L (0.18 vs 0.52 mmol/L per h; P < 0.001) were significantly lower. Hypoglycemia (glucose <3.8 mmol/L) was not observed during the mitiglinide/voglibose phase, but occurred 0.35 times/day in those taking glimepiride. Moreover, the mitiglinide/voglibose phase had higher premeal and lower post-meal glucose levels than the glimepiride phase.. Adding mitiglinide/voglibose to vildagliptin therapy results in more efficient postprandial glucose control and less hypoglycemia than adding glimepiride.

Topics: Adult; Aged; Blood Glucose; Cross-Over Studies; Diabetes Mellitus, Type 2; Dipeptidyl-Peptidase IV Inhibitors; Drug Therapy, Combination; Female; Humans; Hypoglycemia; Hypoglycemic Agents; Inositol; Isoindoles; Male; Middle Aged; Postprandial Period; Sulfonylurea Compounds; Treatment Outcome

Treatment-related quality of life (QOL) is an important aspect of diabetes management. However, no studies have compared the influence of dipeptidyl peptidase-4 inhibitors versus alpha-glucosidase inhibitors on treatment-related QOL. This prespecified sub-analysis of the Linagliptin Study of Effects on Postprandial blood glucose (L-STEP) compared the effects of linagliptin (5 mg once daily) and voglibose (0.2 mg/meal thrice daily) on treatment-related QOL in Japanese patients with type 2 diabetes (T2DM) inadequately controlled with diet and exercise therapy. Among 366 subjects in the original study, 182 in the linagliptin group and 173 in the voglibose group were included in this analysis. The outcome of this study was change in QOL as assessed by the Diabetes Therapy-Related Quality of Life 17 (DTR-QOL17) questionnaire from baseline to week 12. Compared with baseline data, total DTR-QOL17 scores were significantly higher after 12 weeks of linagliptin and voglibose treatment. The change in the total DTR-QOL17 score and the score of one domain, burden on social activities and daily activities, was significantly greater in the linagliptin group than in the voglibose group. In addition, only linagliptin treatment was identified as a factor associated with an increased total DTR-QOL17 score. Linagliptin is superior to voglibose in terms of improving treatment-related QOL in Japanese patients with T2DM.

Topics: Activities of Daily Living; Aged; Blood Glucose; Diabetes Mellitus, Type 2; Dipeptidyl-Peptidase IV Inhibitors; Female; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Inositol; Linagliptin; Male; Middle Aged; Quality of Life; Treatment Outcome

Dipeptidyl peptidase 4 (DPP4) inhibitors improve glycemic control by promoting GLP1-mediated glucose-dependent insulin secretion and suppression of glucagon. Sitagliptin and vildagliptin have been shown to improve insulin sensitivity in patients with type 2 diabetes mellitus (T2DM). However, these patients had uncontrolled blood glucose at inclusion; therefore, the improvement in insulin sensitivity observed in these studies could be attributed to the drug per se and/or reduction in glucotoxicity. This study examines the effect of linagliptin on insulin sensitivity and β-cell function in patients with well-controlled T2DM.. Thirty patients with T2DM of duration ≤5 years, and having HbA1c < 7.5% were randomized to receive linagliptin, voglibose or placebo (n = 10 each), and were followed up for 6 months. Insulin sensitivity was assessed by hyperinsulinemic-euglycemic clamp, and insulin secretory response was measured by basal (M. The median HbA1c of the study subjects at inclusion was 6.9% and there was no significant difference among the groups in terms of age, duration of diabetes, body mass index (BMI), HbA1c, insulin sensitivity, AUC of C-peptide and M. Linagliptin modestly improves glycemic profile in patients with well controlled T2DM; however, it may not have an effect on insulin sensitivity in these patients.. Retrospectively Registered in Clinicaltrials.gov (ID number, NCT02097342 ). Registered: March 27, 2014.

Topics: Adult; Blood Glucose; Diabetes Mellitus, Type 2; Double-Blind Method; Female; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Inositol; Insulin Resistance; Insulin-Secreting Cells; Linagliptin; Male; Middle Aged; Postprandial Period

Topics: Aged; Asian People; Blood Glucose; Diabetes Mellitus, Type 2; Drug Monitoring; Female; Humans; Hypoglycemic Agents; Inositol; Japan; Linagliptin; Male; Middle Aged

BACKGROUND Although the efficacy of combination therapy consisting of basal insulin and oral hypoglycemic agents (OHAs) has been shown, which OHAs are the most efficient remains unclear. MATERIAL AND METHODS Five patients with type 2 diabetes were enrolled and treated with insulin degludec and metformin as a basal therapy. The patients were randomized in a cross-over fashion to receive a combination of mitiglinide (10 mg) and voglibose (0.2 mg) (M+V) 3 times daily or linagliptin (5 mg) (L) once daily for 8 weeks. After 8 weeks, 2 kinds of meal tolerance tests were performed as breakfast on 2 consecutive days. The first breakfast contained 460 kcal (carbohydrates, 49.1%; protein, 15.7%; fat, 35.2%), while the second contained 462 kcal (carbohydrates, 37.2%; protein, 19.6%; fat, 43.2%). Self-monitoring blood glucose levels were measured at 0, 30, 60, and 120 min after the meal tests, and the increase in the postprandial area under the curve (AUC)0-120 min was determined. The HbA1c, glycated albumin, and 1,5-anhydroglucitol (AG) levels were measured, and continuous glucose monitoring was performed. RESULTS The increase in the postprandial AUC0-120 min was significantly smaller in the M+V group than in the L group after both meals. The 24-h average, 24-h standard deviations, 24-h AUC, and mean amplitude of glycemic excursion (MAGE) were similar for both groups and after both meals. The change in 1,5-AG was higher in the M+V group than in the L group. CONCLUSIONS The combination of M+V with basal therapy improved postprandial glucose excursion more effectively than L in T2DM patients.

Topics: Aged; Blood Glucose; Cross-Over Studies; Diabetes Mellitus, Type 2; Dipeptidyl-Peptidases and Tripeptidyl-Peptidases; Humans; Hypoglycemic Agents; Inositol; Insulin; Insulin, Long-Acting; Isoindoles; Linagliptin; Male; Metformin; Middle Aged; Postprandial Period

The purpose of this study was to compare the effects of mitiglinide/voglibose fixed-dose combination and glimepiride on low-density lipoprotein (LDL)-heterogeneity in type-2 diabetic patients with unstable glycemic control after treatment with dipeptidyl peptidase-4 (DPP-4) inhibitors.. This was an open-label pilot study in which type-2 diabetic patients were randomly assigned to the mitiglinide/voglibose (fixed-dose combination of mitiglinide 10 mg and voglibose 0.2 mg, n=14) or glimepiride (0.5 mg, n=16).. In the glimepiride group, serum LDL cholesterol (LDL-C) and small-dense (sd) LDL levels decreased significantly (-8.5% and -9.0%), while sd-LDL/LDL-C and an indicator of LDL-particle size, LDL-C/apoB, did not change significantly. In the mitiglinide/voglibose group, serum LDL-C levels did not change, while sd-LDL levels and sd-LDL/LDL-C decreased significantly (-8.6% and -7.9%) and LDL-C/apoB increased significantly (5.8%). Fasting blood glucose levels tended to be reduced to a greater extent in the glimepiride group than in the mitiglinide/voglibose group (-13.9% vs. -8.4%, p=0.08), while the rate of reduction of HbA1c levels tended to be higher in the mitiglinide/voglibose group than in the glimepiride group (-6.9% vs. -3.4%, p=0.09), suggesting differences in fluctuating blood glucose levels between the 2 groups.. There were differences in the effects of mitiglinide/voglibose fixed-dose combination and glimepiride in addition to DPP-4 inhibitors on LDL-metabolism, and this may be related to fluctuations in blood glucose levels after treatment with these agents.

Topics: Aged; Asian People; Blood Glucose; Diabetes Mellitus, Type 2; Drug Combinations; Female; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Inositol; Isoindoles; Japan; Lipoproteins, LDL; Male; Pilot Projects; Sulfonylurea Compounds

Tofogliflozin is an oral hypoglycemic agent with a novel mechanism of action that reduces blood glucose levels by promoting glucose excretion in urine, achieved by selectively inhibiting sodium-glucose co-transporter 2 (SGLT2). We evaluated the effects of several selected anti-type 2 diabetes mellitus (T2DM) drugs-glimepiride, metformin, sitagliptin, pioglitazone, miglitol, nateglinide, and voglibose-on the pharmacokinetics and pharmacodynamics of tofogliflozin, and the effects of tofogliflozin on the pharmacokinetics of these anti-T2DM drugs in healthy male volunteers.. A single dose of either tofogliflozin alone, one of the anti-T2DM drugs alone, or co-administration of tofogliflozin and the anti-T2DM drug was administered to 108 healthy men. Cmax, AUCinf, and cumulative urine glucose excretion after co-administration of tofogliflozin and each of the anti-T2DM drugs was evaluated relative to the values of those parameters after administration of each drug alone.. None of the anti-T2DM drugs had any effect on tofogliflozin exposure. Tofogliflozin had no or little effect on the exposure of any anti-T2DM drug. No anti-T2DM drug had any major effect on the cumulative urine glucose excretion induced by tofogliflozin. There were no safety concerns evident after administration of any drug alone or in co-administration.. Neither the pharmacokinetics nor the pharmacodynamics of tofogliflozin was affected by any of the anti-T2DM drugs evaluated in this study, nor was the pharmacokinetics of any of the anti-T2DM drugs affected by tofogliflozin in healthy male volunteers.

Topics: 1-Deoxynojirimycin; Adult; Benzhydryl Compounds; Cyclohexanes; Diabetes Mellitus, Type 2; Drug Interactions; Glucose; Glucosides; Healthy Volunteers; Humans; Hypoglycemic Agents; Inositol; Male; Metformin; Middle Aged; Nateglinide; Phenylalanine; Pioglitazone; Sitagliptin Phosphate; Sodium-Glucose Transporter 2 Inhibitors; Sulfonylurea Compounds; Thiazolidinediones; Urine; Young Adult

To compare the therapeutic effects between sitagliptin and voglibose both with sensor-augmented insulin pump (SAP) in newly diagnosed type 2 diabetes mellitus (T2DM).. Fifty-six newly diagnosed hospitalized T2DM patients in Department of Endocrinology of the First Affiliated Hospital of Dalian Medical University, with hemoglobin A1c (HbA1c) value of 9%-11%, were randomized into the sitagliptin (S) group (n=28) and the voglibose (V) group (n=28) by block randomisation. Participants in S group received sitagliptin 100 mg per day, and V group received voglibose 0.2 mg for 3 times per day. All patients were treated with SAP for 9 days. Real-time continuous glucose monitoring (RT-CGM) was used. Glucose variability parameters were observed. The research has been approved by the ethics committee of the First Affiliated Hospital of Dalian Medical University(KY2014-08).. No significant differences were observed in baseline characteristics between the two groups (all P>0.05). In V group and S group, fasting blood glucose (FPG) [(6.4±1.1) vs (11.4±3.0) mmol/L, P=0.008; (5.5±0.8) vs (11.0±2.1) mmol/L, P<0.001], mean blood glucose(MBG) [(7.5±0.8) vs (12.0±1.1) mmol/L, P=0.045; (6.7±0.7) vs (12.5±1.3) mmol/L, P=0.002], standard deviation of blood glucose (SDBG) (P=0.023, 0.036) decreased and homeostasis model assessment (HOMA)-β (P=0.002, 0.001) increased significantly after 9 days therapy. The mean of daily differences (MODD)(P=0.027), coefficient of variation-FPG (CV-FPG) (P=0.033) and HOMA-IR (P=0.039) in S group significantly decreased, while postprandial glycemic excursion (PPGE)(P=0.003, 0.026, 0.011, 3 meals respectively)and the low glycemic index(LBGI)(P=0.025) in V group decreased, the peak postprandial level of glucose(Δt)was longer compared with before (P=0.028, 0.026, 0.030, 3 meals respectively). After therapy, PPGE in V group significantly became lower than those in S group (P=0.041, 0.032, 0.036, 3 meals respectively), while FPG and MBG in S group were significantly lower than those in V group (P=0.041, 0.039).. Sitagliptin or voglibose combined with SAP can improve glucose control and protect islet function for patients with newly diagnosed T2DM. Sitagliptin has advantages in controlling MBG and FPG compared with voglibose. Voglibose has more striking advantages in reducing the postprandial blood glucose fluctuation.

Topics: Blood Glucose; Diabetes Mellitus, Type 2; Glucose; Glucose Tolerance Test; Glycated Hemoglobin; Humans; Hyperinsulinism; Inositol; Insulin Infusion Systems; Insulins; Postprandial Period; Sitagliptin Phosphate

To compare the efficacy on glycemic parameters between a 12-week administration of once-daily linagliptin and thrice-daily voglibose in Japanese patients with type 2 diabetes.. In a multi-center, randomized, parallel-group study, 382 patients with diabetes were randomized to the linagliptin group (n=192) or the voglibose group (n=190). A meal tolerance test was performed at weeks 0 and 12. Primary outcomes were the change from baseline to week 12 in serum glucose levels at 2h during the meal tolerance test, HbA1c levels, and serum fasting glucose levels, which were compared between the 2 groups.. Whereas changes in serum glucose levels at 2h during the meal tolerance test did not differ between the groups, the mean change in HbA1c levels from baseline to week 12 in the linagliptin group (-0.5±0.5% [-5.1±5.4mmol/mol]) was significantly larger than in the voglibose group (-0.2±0.5% [-2.7±5.4mmol/mol]). In addition, there was significant difference in changes in serum fasting glucose levels (-0.51±0.95mmol/L in the linagliptin group vs. -0.18±0.92mmol/L in the voglibose group, P<0.001). The incidences of hypoglycemia, serious adverse events (AEs), and discontinuations due to AEs were low and similar in both groups. However, gastrointestinal AEs were significantly lower in the linagliptin group (1.05% vs. 5.85%; P=0.01).. These data suggested that linagliptin monotherapy had a stronger glucose-lowering effect than voglibose monotherapy with respect to HbA1c and serum fasting glucose levels, but not serum glucose levels 2h after the start of the meal tolerance test.

Topics: Adult; Blood Glucose; Diabetes Mellitus, Type 2; Dose-Response Relationship, Drug; Double-Blind Method; Female; Follow-Up Studies; Humans; Hypoglycemic Agents; Inositol; Japan; Linagliptin; Male; Middle Aged; Postprandial Period; Retrospective Studies; Time Factors; Young Adult

Unlike in western countries, premixed insulin is widely used as the starter insulin in Asian patients instead of basal insulin. The use of basal-bolus therapy as an intensification regimen is not common in Asia despite poor glycaemic control after starting insulin therapy. An alternative insulin intensification regimen with a similar efficacy and safety profile to basal-bolus therapy, but of higher convenience, is urgently needed. The efficacy and safety of insulin lispro mix thrice-daily was compared with basal-bolus therapy in Asian patients with type 2 diabetes who were insufficiently controlled on twice-daily premixed insulin.. This open-label, randomised, active comparator-controlled, parallel-group trial was done at 24 centres in China, Taiwan, and South Korea. Patients with type 2 diabetes who were inadequately controlled on twice-daily premixed insulin were randomly assigned (1:1) to receive either insulin lispro mix (mix 50 before breakfast and lunch plus mix 25 before dinner) or basal-bolus therapy (insulin glargine at bedtime plus prandial insulin lispro thrice-daily) for 24 weeks. Randomisation was done by a computer-generated random sequence and was stratified by country or region and baseline HbA1c. Treatment assignments were masked from the study team assessing outcomes but not from investigators and patients. The primary outcome was change from baseline in HbA1c at week 24 in all randomly assigned patients who received at least one dose of study drug. Analysis was by modified intention to treat, with the per-protocol population used as a supportive analysis. This study is registered with ClinicalTrials.gov, number NCT01175811.. Between Feb 7, 2011, and Nov 7, 2012, 402 patients were enrolled (199 in the premix group, 203 in the basal-bolus group) and 399 were included in the primary analysis (197 in the premix group, 202 in the basal-bolus group). HbA1c change at week 24 was -1.1% for both treatment groups. The least squares mean difference between groups in HbA1c change from baseline was 0% (95% CI -0.1 to 0.2). Insulin lispro mix was non-inferior to basal-bolus therapy based on the prespecified margin of 0.4%. The frequency of adverse events, and the incidences and 30-day rates of nocturnal and overall hypoglycaemia were comparable between groups. No severe hypoglycaemia was reported.. A premixed insulin lispro regimen thrice-daily was non-inferior to basal-bolus therapy in terms of overall glycaemic control and thus could be an option for intensified insulin regimen in Asian patients with type 2 diabetes who are inadequately controlled with twice-daily premixed insulin.

Topics: Acarbose; Aged; China; Diabetes Mellitus, Type 2; Drug Therapy, Combination; Female; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Inositol; Insulin Glargine; Insulin Lispro; Male; Metformin; Middle Aged; Republic of Korea; Taiwan; Treatment Outcome

Left ventricular (LV) diastolic dysfunction is frequently observed in patients with type 2 diabetes. Dipeptidyl peptidase-4 inhibitor (DPP-4i) attenuates postprandial hyperglycemia (PPH) and may have cardio-protective effects. It remains unclear whether DPP-4i improves LV diastolic function in patients with type 2 diabetes, and, if so, it is attributable to the attenuation of PPH or to a direct cardiac effect of DPP-4i. We compared the effects of the DPP-4i, sitagliptin, and the alpha-glucosidase inhibitor, voglibose, on LV diastolic function in patients with type 2 diabetes.. We conducted a prospective, randomized, open-label, multicenter study of 100 diabetic patients with LV diastolic dysfunction. Patients received sitagliptin (50 mg/day) or voglibose (0.6 mg/day). The primary endpoints were changes in the e' velocity and E/e' ratio from baseline to 24 weeks later. The secondary efficacy measures included HbA1c, GLP-1, lipid profiles, oxidative stress markers and inflammatory markers.. The study was completed with 40 patients in the sitagliptin group and 40 patients in the voglibose group. There were no significant changes in the e' velocity and E/e' ratio from baseline to 24 weeks later in both groups. However, analysis of covariance demonstrated that pioglitazone use is an independent factor associated with changes in the e' and E/e' ratio. Among patients not using pioglitazone, e' increased and the E/e' ratio decreased in both the sitagliptin and voglibose groups. GLP-1 level increased from baseline to 24 weeks later only in the sitagliptin group (4.8 ± 4.7 vs. 7.3 ± 5.5 pmol/L, p < 0.05). The reductions in HbA1c and body weight were significantly greater in the sitagliptin group than in the voglibose group (-0.7 ± 0.6 % vs. -0.3 ± 0.4, p < 0.005; -1.3 ± 3.2 kg vs. 0.4 ± 2.8 kg, p < 0.05, respectively). There were no changes in lipid profiles and inflammatory markers in both groups.. Our trial showed that sitagliptin reduces HbA1c levels more greatly than voglibose does, but that neither was associated with improvement in the echocardiographic parameters of LV diastolic function in patients with diabetes.. Registered at http://www.umin.ac.jp under UMIN000003784.

Topics: Aged; Diabetes Mellitus, Type 2; Diastole; Dipeptidyl-Peptidase IV Inhibitors; Echocardiography; Female; Glucagon-Like Peptide 1; Glycated Hemoglobin; Glycoside Hydrolase Inhibitors; Humans; Inositol; Male; Middle Aged; Sitagliptin Phosphate; Treatment Outcome; Ventricular Dysfunction, Left

This trial was conducted to compare the efficacy and safety of combination therapy with basal insulin glargine plus mitiglinide to that of basal insulin glargine plus voglibosein patients with type 2 diabetes. This was a 20-week, randomized, multicenter non-inferiority trial. Patients with HbA1c levels over 7.0% were randomly assigned to receive either mitiglinide (10 mg tid) or voglibose (0.2 mg tid) concurrent with insulin glargine for 16 weeks after a 4-week of basal insulin glargine monotherapy. The intention-to-treat population included 156 patients; 79 were placed in the mitiglinide group, and 77 were placed in the voglibose group. At 20 weeks, there was no significant difference between the mitiglinide group and the voglibose group in terms of the mean HbA1c level or the mean decrease of the HbAlc level from baseline (-0.9% [-7.5 mmol/mol] and -0.7%, [-5.3 mmol/mol] respectively). The mean fasting plasma glucose level and data of self-monitoring blood glucosewere significantly decreased from baseline to week 20 in both groups, but there was no significant difference between the two groups. The changes in the basal insulin requirements of each group were not significant. The prevalence of adverse events and the risk of hypoglycemia were similar for both groups. Combination therapy with mitiglinide plus basal insulin glargine was non-inferior to voglibose plus basal insulin glargine in terms of the effect on overall glycemic control.

Topics: Adult; Blood Glucose; Body Mass Index; Diabetes Mellitus, Type 2; Fasting; Female; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Inositol; Insulin Glargine; Isoindoles; Male; Middle Aged; Prospective Studies

Teneligliptin is a novel DPP-4 inhibitor in development for treating type 2 diabetes mellitus that does not require dose adjustment for diabetic patients with end-stage renal disease; however, it had not been known whether or not teneligliptin is safe or potent in dialysis patients. We conducted a prospective study to assess the utility of teneligliptin for diabetic patients undergoing hemodialysis.. Blood glucose, glycated albumin, and HbA1c were measured every 4 weeks, at 4, 12, 20, and 28 weeks, and every 8 weeks, respectively, for patients treated with teneligliptin (n = 14; 7 patients newly started and 7 that switched from other medications) and patients of a control group who continued ongoing antidiabetic therapy (n = 29).. Blood glucose level showed a 36.7 mg/dl decrease from 4 weeks in the teneligliptin group (p < 0.05). The differences in glycated albumin (at 28 w) and HbA1c (at 24 w) between the teneligliptin group and the control group were -3.1 % (p < 0.05) and -0.57 % (p = 0.057), respectively. These parameters also decreased in patients who switched from voglibose 0.2 mg t.i.d. or vildagliptin 50 mg qd after teneligliptin administration. No case with hypoglycemia was identified. One patient had the dose of a laxative administered for constipation increased; however, no patient ceased teneligliptin due to side effects.. Teneligliptin 20 mg is well tolerated, safe, and significantly improves glycemic control in diabetic patients with end-stage renal disease. Teneligliptin 20 mg once daily was considered to be more potent than voglibose 0.2 mg t.i.d. or vildagliptin 50 mg qd.

Topics: Adamantane; Aged; Blood Glucose; Diabetes Mellitus, Type 2; Dipeptidyl-Peptidase IV Inhibitors; Female; Glycated Hemoglobin; Glycated Serum Albumin; Glycation End Products, Advanced; Humans; Hypoglycemic Agents; Inositol; Kidney Failure, Chronic; Male; Middle Aged; Nitriles; Prospective Studies; Pyrazoles; Pyrrolidines; Renal Dialysis; Serum Albumin; Thiazolidines; Vildagliptin

We studied the efficacy and safety of acarbose in comparison with voglibose in type 2 diabetes patients whose blood glucose levels were inadequately controlled with basal insulin alone or in combination with metformin (or a sulfonylurea). This study was a 24-week prospective, open-label, randomized, active-controlled multi-center study. Participants were randomized to receive either acarbose (n=59, 300 mg/day) or voglibose (n=62, 0.9 mg/day). The mean HbA1c at week 24 was significantly decreased approximately 0.7% from baseline in both acarbose (from 8.43% ± 0.71% to 7.71% ± 0.93%) and voglibose groups (from 8.38% ± 0.73% to 7.68% ± 0.94%). The mean fasting plasma glucose level and self-monitoring of blood glucose data from 1 hr before and after each meal were significantly decreased at week 24 in comparison to baseline in both groups. The levels 1 hr after dinner at week 24 were significantly decreased in the acarbose group (from 233.54 ± 69.38 to 176.80 ± 46.63 mg/dL) compared with the voglibose group (from 224.18 ± 70.07 to 193.01 ± 55.39 mg/dL). In conclusion, both acarbose and voglibose are efficacious and safe in patients with type 2 diabetes who are inadequately controlled with basal insulin. (ClinicalTrials.gov number, NCT00970528).

Topics: Acarbose; Blood Glucose; Diabetes Mellitus, Type 2; Enzyme Inhibitors; Female; Glycated Hemoglobin; Glycoside Hydrolase Inhibitors; Humans; Hypoglycemic Agents; Inositol; Insulin; Male; Metformin; Middle Aged; Prospective Studies

We assessed the efficacy and safety of sitagliptin compared with α-glucosidase inhibitor (αGI) in 120 of Japanese patients with type 2 diabetes mellitus (T2DM) inadequately controlled on stable ≤2 mg/day glimepiride alone [mean hemoglobin A1c (HbA1c) 7.7%] by the randomized, active-controlled, non-inferiority trial. Patients were randomly assigned to receive additional sitagliptin or αGI for 24 weeks. The primary endpoint was change in HbA1c from baseline to week 12. After 12 weeks, sitagliptin reduced HbA1c by -0.44% (p < 0.001) relative to αGI. At 24 weeks, the reduction was almost identical between the groups (-0.091%, p = 0.47). Gastrointestinal disorders were more common with αGI than with sitagliptin, but only minor hypoglycaemia occurred in both groups at similar frequency. These data suggested that sitagliptin was not inferior to αGI for reduction of HbA1c in Japanese T2DM patients receiving glimepiride alone, and well tolerated with minimum risk of gastrointestinal symptoms and hypoglycaemia.

Topics: 1-Deoxynojirimycin; Aged; alpha-Glucosidases; Diabetes Mellitus, Type 2; Dipeptidyl-Peptidase IV Inhibitors; Drug Therapy, Combination; Female; Gastrointestinal Agents; Glycated Hemoglobin; Glycoside Hydrolase Inhibitors; Humans; Hyperglycemia; Hypoglycemia; Hypoglycemic Agents; Inositol; Japan; Male; Middle Aged; Pyrazines; Sitagliptin Phosphate; Sulfonylurea Compounds; Triazoles

We investigated the efficacy of once- and thrice-daily voglibose, an alpha-glucosidase inhibitor, as an add-on therapy to alogliptin, a dipeptidyl peptidase-4 inhibitor, on glycemic control in Japanese type 2 diabetic patients. In this 12-week, parallel-group, randomized, open-label, three-arm trial, 151 participants treated with alogliptin were randomly allocated to the following three arms; one was the group to initiate once-daily voglibose, another was to initiate thrice daily voglibose, and the other was the control group. The primary endpoint was the change of hemoglobin A1c levels at the end of the study, which was revealed to be significantly different among groups (p < 0.001). The once- and thrice-daily voglibose groups had a significantly greater reduction than the control group; the difference was -0.27% and -0.33% in the once- and thrice-daily voglibose group, respectively (both p < 0.001). No significant difference was observed between the two voglibose groups (p = 0.615). On the other hand, the increase of 1,5-anhydroglucitol levels were 3.3 and 5.5 μg/ml greater in the once- and thrice-daily voglibose groups than the control group (both p < 0.001). The thrice-daily voglibose group had a greater increase of 1,5- anhydroglucitol levels compared to the once-daily voglibose group (p = 0.005). In conclusion, once- and thrice-daily voglibose as an add-on to alogliptin significantly improved glycemic control in Japanese type 2 diabetic patients.

Topics: Adult; Aged; Asian People; Blood Glucose; Diabetes Mellitus, Type 2; Dipeptidyl-Peptidase IV Inhibitors; Drug Administration Schedule; Female; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Inositol; Male; Middle Aged; Piperidines; Treatment Outcome; Uracil

Postprandial hyperglycemia and blood glucose fluctuations increase the risk of macroangiopathy in patients with type 2 diabetes mellitus (T2DM). However, few studies have examined the effects of oral hypoglycemic drugs on blood glucose fluctuations in daily life.. Twenty-nine T2DM patients treated with acarbose were randomized to receive either sitagliptin (14 patients) or mitiglinide (15 patients) together with acarbose for 4 weeks. Patients were then switched to a combination of 10 mg mitiglinide and 0.2 mg voglibose for 4 weeks. All patients wore a continuous glucose monitoring (CGM) device for 5 - 7 days in week 3 of each treatment period.. The percentage of blood glucose levels in the hyperglycemic range, blood glucose indices derived from 24-h CGM profiles and the glycemic parameters (HbA1c, glycated albumin and fasting plasma glucose) were significantly improved by adding sitagliptin or mitiglinide to ongoing acarbose therapy. These parameters also tended to improve in the mitiglinide/voglibose combination period.. Daily blood glucose fluctuations were significantly improved by adding sitagliptin or mitiglinide to acarbose, and improved after switching to the mitiglinide/voglibose combination. Larger controlled studies are needed to verify the effects of adding sitagliptin or mitiglinide to acarbose on glucose fluctuations.

Topics: Acarbose; Aged; Asian People; Blood Glucose; Diabetes Mellitus, Type 2; Drug Substitution; Drug Therapy, Combination; Female; Glycated Serum Albumin; Glycation End Products, Advanced; Humans; Hyperglycemia; Hypoglycemic Agents; Inositol; Isoindoles; Male; Middle Aged; Prospective Studies; Pyrazines; Serum Albumin; Sitagliptin Phosphate; Triazoles

The effects of the mitiglinide/voglibose fixed-dose combination on postprandial glycemic/metabolic responses in patients with type 2 diabetes mellitus (T2DM) treated with dipeptidyl peptidase-4 (DPP-4) inhibitors are unknown.. Twelve T2DM patients treated with a DPP-4 inhibitor underwent identical meal tolerance tests (MTTs) at breakfast, lunch and dinner, before and 2 - 3 weeks after treatment with a fixed-dose combination of mitiglinide 10 mg and voglibose 0.2 mg (combination). Patients were randomized in a cross-over fashion to administer the combination either three-times-daily before each meal or twice-daily before breakfast and dinner. Glycemic/metabolic responses were evaluated at 0, 30, 60 and 120 min in each MTT.. Three-times-daily administration of the combination significantly suppressed postprandial hyperglycemia after each meal, particularly after lunch and dinner. Active glucagon-like peptide-1 levels increased significantly after each meal, as did early-phase insulin secretion without excessive insulin secretion. Postprandial hyperglycemia after lunch was significantly greater after twice-daily than three-times-daily administration, but there were no clinically relevant differences in other metabolic responses.. This study revealed that adding the mitiglinide/voglibose combination to a DPP-4 inhibitor elicited additive improvements in postprandial glycemic/metabolic responses assessed using MTTs at breakfast, lunch and dinner with identical meal compositions.

Topics: Aged; Blood Glucose; Breakfast; Diabetes Mellitus, Type 2; Dipeptidyl-Peptidase IV Inhibitors; Drug Combinations; Drug Therapy, Combination; Female; Glucagon-Like Peptide 1; Humans; Hyperglycemia; Hypoglycemic Agents; Inositol; Insulin; Insulin Secretion; Isoindoles; Lunch; Male; Meals; Middle Aged; Postprandial Period

Alpha glucosidase inhibitor (GI) attenuates postprandial hyperglycemia (PPH) and reduces the risk of cardiovascular events in patients with impaired glucose tolerance or type 2 diabetes. Dipeptidyl peptidase 4 (DPP-4) inhibitors also attenuate PPH. PPH is one of the factors leading to endothelial dysfunction which is an early event in the pathogenesis of atherosclerosis. Furthermore, DPP-4 inhibitors protect endothelial function through a GLP-1-dependent mechanism. However, the impact of these two types of drugs on endothelial dysfunction in patients with type 2 diabetes has not been fully elucidated. We compared the effects of sitagliptin, a DPP-4 inhibitor, and voglibose, an alpha GI, on endothelial function in patients with diabetes.. We conducted a randomized prospective multicenter study in 66 patients with type 2 diabetes who did not achieve the treatment goal with sulfonylurea, metformin or pioglitazone treatment; 31 patients received sitagliptin treatment and 35 patients, voglibose treatment. The flow-mediated dilatation (FMD) of the brachial artery was measured in the fasting state at baseline and after 12 weeks of treatment. The primary endpoint was a change in FMD (ΔFMD) from the baseline to the end of follow-up. The effects of sitagliptin and voglibose on FMD were assessed by ANCOVA after adjustment for the baseline FMD, age, sex, current smoking, diabetes duration and body mass index. Secondary efficacy measures included changes in HbA1c, GIP, GLP-1, C-peptide, CD34, lipid profile, oxidative stress markers, inflammatory markers and eGFR and any adverse events.. ΔFMD was significantly improved after 12 weeks of treatment in both groups, and there was no significant difference in ΔFMD between the two groups. There were no significant differences in changes in HbA1c, GIP, GLP-1, C-peptide, lipid profile, oxidative stress marker, inflammatory marker and eGFR between the two groups. Compared with voglibose, sitagliptin significantly increased the circulating CD34, a marker of endothelial progenitor cells. Adverse events were observed in 5 patients in only the voglibose group (diarrhea 1, nausea 1, edema 2 and abdominal fullness 1).. Sitagliptin improved endothelial dysfunction just as well as voglibose in patients with type 2 diabetes. Sitagliptin had protective effects on endothelial function without adverse events.. registered at http://www.umin.ac.jp/ctrj/ under UMIN000003951.

Topics: Adult; Aged; Aged, 80 and over; Diabetes Mellitus, Type 2; Dipeptidyl-Peptidase IV Inhibitors; Endothelium, Vascular; Female; Glycoside Hydrolase Inhibitors; Humans; Inositol; Male; Middle Aged; Prospective Studies; Pyrazines; Sitagliptin Phosphate; Triazoles; Young Adult

In this study we examined the effects of switching α-glucosidase inhibitors (α-GI) from acarbose or voglibose to miglitol on glucose fluctuations and circulating concentrations of cardiovascular disease risk factors, such as soluble adhesion molecules (sE-selectin, sICAM-1 and sVCAM-1), a chemokine monocyte chemoattractant protein (MCP)-1, plasminogen activator inhibitor-1, and fatty acid-binding protein 4, in type 2 diabetic patients for 3 months.. We enrolled 47 Japanese patients with type 2 diabetes, with HbA1c levels with 7.26 ± 0.5 % (mean ± standard deviation), and who were treated with the highest approved dose of acarbose (100 mg/meal) or voglibose (0.3 mg/meal) in combination with insulin or sulfonylurea. Patients' prior α-GIs were switched to a medium dose of miglitol (50 mg/meal), and the new treatments were maintained for 3 months. Thirty-five patients who completed the 3-month study and provided serum samples were analyzed.. The switch to miglitol for 3 months did not affect HbA1c, fasting glucose, triglycerides, total-cholesterol or C-reactive protein levels, or result in any adverse events. Glucose fluctuations were significantly improved by the change in treatment (M-value: 10.54 ± 4.32 to 8.36 ± 2.54), while serum protein concentrations of MCP-1 (525.04 ± 288.06-428.11 ± 163.78 pg/mL) and sE-selectin (18.65 ± 9.77-14.50 ± 6.26 ng/mL) were suppressed.. Our results suggest that switching from acarbose or voglibose to miglitol for 3 months suppressed glucose fluctuations and serum protein levels of MCP-1 and sE-selectin in type 2 diabetic Japanese patients, with fewer adverse effects.

Topics: 1-Deoxynojirimycin; Acarbose; Aged; Asian People; Blood Glucose; Cardiovascular Diseases; Chemokine CCL2; Diabetes Mellitus, Type 2; Drug Therapy, Combination; E-Selectin; Female; Glycoside Hydrolase Inhibitors; Humans; Hypoglycemic Agents; Inositol; Insulin; Male; Middle Aged; Prospective Studies; Risk Factors; Time Factors

We examined the effects of a fixed-dose combination of 10 mg mitiglinide and 0.2 mg voglibose on postprandial glycemic excursions in Japanese type 2 diabetes mellitus (T2DM) patients.. After a 2-week baseline period, 11 T2DM patients were treated with mitiglinide alone for 2 weeks and with the mitiglinide/voglibose combination for 6 weeks.. Self-monitoring of blood glucose (SMBG) at home before and after unified meals, metabolic parameters during meal tolerance tests, and overall glycemic control parameters.. Postprandial glycemic excursions after all three meals, as assessed by SMBG, were significantly lower in the combination period than in the baseline period, and after lunch and dinner in the combination period than in the mitiglinide period. The meal tolerance test confirmed that the magnitude of postprandial hyperglycemia was significantly lower, with significantly greater early-phase serum insulin secretion and sustained GLP-1 production, in the combination period compared with the baseline period. Overall glycemic control parameters also improved significantly in the combination period compared with the baseline period. These profiles suggest the combination is superior to mitiglinide alone, and may spare insulin secretion.. The mitiglinide/voglibose combination significantly reduced postprandial glycemic excursions in Japanese T2DM patients. This trial was registered with the University Hospital Medical Information Network clinical trials database (no. UMIN000007202).

Topics: Blood Glucose; Diabetes Mellitus, Type 2; Drug Administration Schedule; Drug Combinations; Female; Humans; Hyperglycemia; Hypoglycemic Agents; Inositol; Isoindoles; Japan; Lipids; Male; Middle Aged; Postprandial Period; Treatment Outcome

Endothelial dysfunction is an independent predictor for cardiovascular events in patients with type 2 diabetes (T2DM). Glucagon like peptide-1 (GLP-1) reportedly exerts vasodilatory actions, and inhibitors of dipeptidyl peptidase-4 (DPP-4), an enzyme-degrading GLP-1, are widely used to treat T2DM. We therefore hypothesized that DPP-4 inhibitors (DPP-4Is) improve endothelial function in T2DM patients and performed 2 prospective, randomized crossover trials to compare the DPP-4I sitagliptin and an α-glucosidase inhibitor, voglibose (in study 1) and the DPP-4Is sitagliptin and alogliptin (in study 2).. In study 1, 24 men with T2DM (46±5 years) were randomized to sitagliptin or voglibose for 6 weeks without washout periods. Surprisingly, sitagliptin significantly reduced flow-mediated vasodilatation (FMD; -51% compared with baseline, P<0.05) of the brachial artery despite improved diabetic status. In contrast, voglibose did not affect FMD. To confirm this result and determine whether it is a class effect, we conducted another trial (study 2) to compare sitagliptin and alogliptin in 42 T2DM patients (66±8 years) for 6 weeks with 4-week washout periods. Both DPP-4Is improved glycemic control but significantly attenuated FMD (7.2/4.3%, P<0.001, before/after sitagliptin; 7.0/4.8%, P<0.001, before/after alogliptin, respectively). Interestingly, FMD reduction was less evident in subjects who were on statins or whose LDL cholesterol levels were reduced by them, but this was not correlated with parameters including DPP-4 activity and GLP-1 levels or diabetic parameters.. Our 2 independent trials demonstrated that DPP-4 inhibition attenuated endothelial function as evaluated by FMD in T2DM patients. This unexpected unfavorable effect may be a class effect of DPP-4Is.. URL: http://center.umin.ac.jp, Unique Identifiers: UMIN000005682 (sitagliptin versus voglibose) and UMIN000005681 (sitagliptin versus alogliptin).

Topics: Adult; Aged; Biomarkers; Blood Glucose; Cholesterol, LDL; Cross-Over Studies; Diabetes Mellitus, Type 2; Dipeptidyl-Peptidase IV Inhibitors; Endothelium, Vascular; Female; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Inositol; Japan; Linear Models; Male; Middle Aged; Piperidines; Prospective Studies; Pyrazines; Regional Blood Flow; Sitagliptin Phosphate; Time Factors; Treatment Outcome; Triazoles; Uracil; Vasodilation

To assess the extent of pharmacokinetic and pharmacodynamic interaction between vildagliptin, a potent and selective inhibitor of dipeptidyl peptidase IV (DPP-4) enzyme, and voglibose, an α-glucosidase inhibitor widely prescribed in Japan, when coadministered in Japanese patients with Type 2 diabetes.. In this open-label, randomized, 3-treatment, 3-period and 6-way crossover study, 24 Japanese patients with Type 2 diabetes received 50 mg vildagliptin twice daily; 50 mg vildagliptin twice daily co-administered with 0.2 mg voglibose three times daily; or 0.2 mg voglibose three times daily for 3 days in each period. Plasma concentrations of vildagliptin, DPP-4, glucagon-like peptide-1 (GLP-1), glucose, insulin, and glucagon were determined from blood samples collected at steady state.. Exposure to vildagliptin 50 mg (area under the concentration-time curve from 0 to 12 hours (AUCτ,ss)) and maximum plasma concentration at steady state (Cmax,ss) was reduced by 23% and 34% respectively with co-administration of voglibose. The percentage of DPP-4 inhibition by vildagliptin remained unchanged when vildagliptin was given alone or co-administered with voglibose; maximum inhibition was 98.3 ± 1.4% (mean ± SD) for vildagliptin alone and 97.4 ± 1.1% with co-administration. Coadministration of vildagliptin and voglibose led to a greater increase in the active GLP-1 plasma concentration than did vildagliptin alone (geometric mean ratio 1.63 (90% CI, 1.30, 2.03), p = 0.0007). The combination of vildagliptin and voglibose also led to a significantly lower plasma glucose levels (p < 0.0001).. Plasma vildagliptin levels were decreased when voglibose was co-administered, although DPP- 4 inhibition remained unchanged. Co-administration led to significantly better pharmacodynamic response compared with each treatment alone, including higher active GLP-1 and lower glucose levels. The results indicate that this coadministration may be beneficial in the clinical situation. Vildagliptin and voglibose treatments, alone or when co-administered, were well tolerated in Japanese patients with Type 2 diabetes.

Topics: Adamantane; Adult; Blood Glucose; Cross-Over Studies; Diabetes Mellitus, Type 2; Dipeptidyl-Peptidase IV Inhibitors; Drug Interactions; Female; Glucagon; Glucagon-Like Peptide 1; Glycoside Hydrolase Inhibitors; Humans; Hypoglycemic Agents; Inositol; Insulin; Male; Middle Aged; Nitriles; Pyrrolidines; Vildagliptin

The postprandial glucose (PPG) level is reduced by α-GIs, glinides and DPP4Is through different pharmacological actions. The aim of this study was to compare the effect of sitagliptin (S) versus that of the combination of mitiglinide and voglibose (M+V) on markers of glycemic control.. A randomized cross-over trial was performed in 20 patients with drug-naïve type 2 diabetes. The patients were randomized to receive S (50 mg/day) or M+V (1 tablet 3 times daily). Treatment was continued for 8 weeks, after which they were switched to the other regimen and treated for another 8 weeks. At baseline, after the first regimen, and after the second regimen, a meal test was performed.. The markers of glycemic control were examined.. Reduction of glucose excursion was significantly greater with M+V than with S. HbA1c did not change with either regimen. However, 1,5-anhydroglucitol showed a significant increase from baseline with both regimens (7.9 ± 4.3 μg/ml at baseline vs. 10.6 ± 5.5 with S, p < 0.05 and 15.1 ± 6.2 with M+V, p < 0.01). Compared with baseline, glycoalbumin was significantly reduced by M+V, but not S (19.6 ± 2.9% at baseline vs. 17.3 ± 3.8% with M+V, p < 0.05).. M+V achieved better control of PPG excursion than S.

Topics: Aged; Asian People; Blood Glucose; Cross-Over Studies; Deoxyglucose; Diabetes Mellitus, Type 2; Drug Combinations; Female; Glycated Hemoglobin; Glycated Serum Albumin; Glycation End Products, Advanced; Humans; Hypoglycemic Agents; Inositol; Insulin; Isoindoles; Male; Middle Aged; Pyrazines; Serum Albumin; Sitagliptin Phosphate; Triazoles

In a phase III study conducted among Japanese patients with type 2 diabetes mellitus (T2DM), linagliptin 5 and 10 mg showed clinically meaningful improvements in glycaemic parameters after 12 and 26 weeks compared with placebo and voglibose, respectively. This extension study assessed long-term tolerability of linagliptin over 52 weeks.. Japanese patients with T2DM who completed either phase of a 12-week/26-week study comparing linagliptin monotherapy with placebo or voglibose were eligible to enrol. In the extension study, the comparator groups switched to linagliptin 5 or 10 mg, while the linagliptin groups maintained dosage.. In all, 540 patients received at least one dose of linagliptin 5 or 10 mg and 494 completed the extension. Long-term treatment with linagliptin was well tolerated; adverse events (AEs) of special interest and serious AEs occurred in small percentages of patients. Drug-related AEs occurred in 10.2 and 10.6% of patients in the linagliptin 5- and 10-mg groups, respectively, and discontinuations due to drug-related AEs occurred in 1.1 and 0.7%, respectively. Only one (0.4%) patient in each dose group experienced investigator-defined hypoglycaemia during the treatment period (both events were non-severe). Body weight was not clinically altered in either group. The glycated haemoglobin A1c profiles over time were similar with linagliptin 5 and 10 mg.. These findings provide evidence for the safety and tolerability of oral linagliptin at either 5 or 10 mg for up to 52 weeks for the treatment of Japanese patients with T2DM, without clinically relevant increase in the risk of hypoglycaemia or weight gain.

Topics: Adult; Aged; Aged, 80 and over; Asian People; Blood Glucose; Body Mass Index; Body Weight; Diabetes Mellitus, Type 2; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Female; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Inositol; Linagliptin; Male; Middle Aged; Purines; Quinazolines; Time Factors

To compare the effects of miglitol [an alpha-glucosidase inhibitor (AGI) absorbed in the intestine] and voglibose (an AGI not absorbed) on plasma glucagon-like peptide-1 (GLP-1) and gastric inhibitory polypeptide (GIP) levels, 26 and 24 Japanese type 2 diabetic patients were randomly assigned to receive miglitol or voglibose, respectively. After 12-week administration of both drugs, during 2-h meal tolerance test, plasma glucose, serum insulin and total GIP were significantly decreased and active GLP-1 was significantly increased. Miglitol group showed a significantly lower total GIP level than voglibose group. Miglitol, but not voglibose, significantly reduced body weight (BW). In all participants, the relative change in BW was positively correlated with that of insulin significantly and of GIP with a weak tendency, but not of GLP-1. In conclusion, both drugs can enhance postprandial GLP-1 responses and reduce GIP responses. The significant BW reduction by miglitol might be attributable to its strong GIP-reducing efficacy.

Topics: 1-Deoxynojirimycin; Asian People; Diabetes Mellitus, Type 2; Drug Administration Schedule; Female; Gastric Inhibitory Polypeptide; Glucagon-Like Peptide 1; Humans; Hypoglycemic Agents; Incretins; Inositol; Male; Middle Aged; Obesity; Postprandial Period

To evaluate the efficacy and safety of linagliptin 5 and 10 mg vs. placebo and voglibose in Japanese patients with type 2 diabetes mellitus (T2DM).. This study enrolled patients with inadequately controlled T2DM who were previously treated with one or two oral antidiabetics or were drug naÏve. After a 2 to 4-week washout and placebo run-in, 561 patients were randomized (2 : 2 : 2 : 1) to double-blind treatment with linagliptin 5 or 10 mg qd, voglibose 0.2 mg tid or placebo. The primary endpoint was the change from baseline in haemoglobin A1c (HbA1c) with linagliptin vs. placebo after 12 weeks and vs. voglibose after 26 weeks.. Baseline characteristics were well balanced across treatment groups (overall mean HbA1c was 8.01%). The adjusted mean (95% confidence interval) treatment differences at week 12 were -0.87% (-1.04, -0.70; p < 0.0001) and -0.88% (-1.05, -0.71; p < 0.0001) for linagliptin 5 and 10 mg vs. placebo and at week 26 were -0.32% (-0.49, -0.15; p = 0.0003) and -0.39% (-0.56, -0.21; p < 0.0001) for linagliptin 5 and 10 mg vs. voglibose. At week 12, mean HbA1c was 7.58, 7.48 and 8.34% in patients receiving linagliptin 5 mg, linagliptin 10 mg and placebo, respectively. At week 26, mean HbA1c was 7.63% with linagliptin 5 mg, 7.50% with linagliptin 10 mg and 7.91% with voglibose. Drug-related adverse event rates were comparable across treatment groups over 12 weeks (9.4% linagliptin 5 mg, 8.8% linagliptin 10 mg and 10.0% placebo) and 26 weeks (11.3% linagliptin 5 mg, 10.6% linagliptin 10 mg and 18.5% voglibose). There were no documented cases of hypoglycaemia.. Linagliptin showed superior glucose-lowering efficacy and comparable safety and tolerability to both placebo and voglibose in Japanese patients with T2DM.

Topics: Adult; Aged; Aged, 80 and over; Analysis of Variance; Blood Glucose; Diabetes Mellitus, Type 2; Dipeptidyl-Peptidase IV Inhibitors; Dose-Response Relationship, Drug; Double-Blind Method; Drug Administration Schedule; Female; Humans; Hypoglycemic Agents; Inositol; Japan; Linagliptin; Male; Middle Aged; Purines; Quinazolines; Treatment Outcome

The additive effect of α-glucosidase inhibitors (α-GIs) was investigated in patients with type 2 diabetes (T2D) under control with rapid-acting insulin analog.. Thirty-six poorly controlled T2D patients were recruited, and plasma glucose (PG) was controlled by three times daily injection of insulin lispro mix 50/50 (Mix50) to maintain fasting PG <130 mg/dL and 2-h postprandial PG (PPG) <180 mg/dL. Another group of 20 patients was randomly assigned to either 0.3 mg of voglibose or 50 mg of miglitol, which was administered at breakfast every other day. Another group of 16 patients was assigned to a crossover study, in which each α-GI was switched every day during the 6-day study. PPG, C-peptide, and lipid profile were analyzed.. The addition of voglibose had no effect on PPG, but miglitol blunted the PPG rise and significantly decreased 1-h and 2-h postprandial C-peptide levels compared with Mix50 alone. In addition, miglitol significantly decreased the 1-h postprandial triglyceride rise and the remnant-like particle-cholesterol rise, while it increased the 1-h postprandial high-density lipoprotein-cholesterol and apolipoprotein A-I levels in the crossover study.. Miglitol appears to have rapid action, which appears earlier than that of lispro. The combination of miglitol and Mix50 seems effective for the control of PPG and lipid profile in T2D.

Topics: 1-Deoxynojirimycin; Apolipoprotein A-I; Blood Glucose; C-Peptide; Cross-Over Studies; Diabetes Mellitus, Type 2; Enzyme Inhibitors; Female; Glycoside Hydrolase Inhibitors; Humans; Hypoglycemic Agents; Inositol; Insulin Lispro; Lipids; Lipoproteins, HDL; Male; Middle Aged; Postprandial Period; Treatment Outcome; Triglycerides

The objective of this study was to compare the effects of mitiglinide, voglibose and its combination on metabolic responses after a test meal in Japanese patients with type 2 diabetes mellitus (T2DM).. This randomized crossover study consisted of four periods between August and November 2011. In the first period, all patients (n = 12) received water alone (control period). In the next three periods, the patients received 10 mg mitiglinide, 0.2 mg voglibose or a combination in a random order.. Postprandial metabolite/hormone levels were then measured.. Plasma glucose and serum insulin reached peak levels by 60 - 90 and 90 min, respectively, after the test meal in the control group. The combination reduced postprandial glucose levels compared with mitiglinide or voglibose alone, particularly at 30 - 90 min, which significantly exceeded the effects of mitiglinide (p < 0.05). Mitiglinide and the combination restored early insulin response, whereas the combination provided an insulin-sparing effect compared with mitiglinide alone. The combination improved postprandial lipid profiles, combining the effects of both drugs.. This study revealed marked differences in the postprandial metabolic effects of mitiglinide, voglibose and its combination in patients with T2DM. The combination therapy should enable tighter control of postprandial hyperglycemia compared with the individual drugs.

Topics: Aged; Asian People; Blood Glucose; Cross-Over Studies; Diabetes Mellitus, Type 2; Drug Combinations; Female; Glucagon; Humans; Hyperglycemia; Hypoglycemic Agents; Inositol; Insulin; Isoindoles; Male; Middle Aged

Type 2 diabetes mellitus (T2DM) associated with metabolic syndrome (MetS) represents a high risk of cardiovascular disease. We compared the effect of early intervention with pioglitazone versus voglibose on physical and metabolic profiles and serum adiponectin level in patients with T2DM associated with MetS. Sixty patients who were diagnosed for the first time as T2DM associated with MetS were analyzed for insulin sensitivity, lipid profile, serum adiponectin and systemic inflammation. Those patients were randomly assigned to oral pioglitazone group (n = 30) or voglibose group (n = 30) in addition to conventional diet and exercise training. Body mass index and waist circumference did not change in the pioglitazone group, whereas these physical parameters significantly decreased in the voglibose group during a 6-month follow-up period. However, glycosylated hemoglobin, fasting plasma glucose, and HOMA-IR more significantly decreased in the pioglitazone group. The level of serum adiponectin especially high-molecular weight adiponectin markedly increased in the pioglitazone group. Moreover, high sensitive CRP significantly decreased only in the pioglitazone group. These results suggest that voglibose is superior in improving obesity, while pioglitazone is superior in ameliorating insulin sensitivity and increasing serum adiponectin in patients with an early stage of T2DM associated with MetS.

Topics: Adiponectin; Diabetes Mellitus, Type 2; Glycoside Hydrolase Inhibitors; Humans; Hypoglycemic Agents; Inositol; Insulin Resistance; Metabolic Syndrome; Metabolome; Obesity; Pioglitazone; Thiazolidinediones

Topics: Adult; Aged; Diabetes Mellitus, Type 2; Double-Blind Method; Female; Glucose Intolerance; Humans; Hypoglycemic Agents; Inositol; Male; Metabolic Syndrome; Middle Aged

To compare the efficacy and safety of alogliptin and placebo as add-on therapy in Japanese patients with type 2 diabetes who experienced inadequate glycemic control on voglibose plus diet/exercise therapy.. During an 8 week screening phase, patients aged ≥ 20 years were stabilized on voglibose 0.2 mg three times daily plus diet/exercise therapy. Those with HbA1c between ≥ 6.9% and <10.4% were randomly assigned to 12 weeks' double-blind treatment with once daily alogliptin 12.5 or 25 mg, or placebo. The primary endpoint was the change in HbA1c at 12 weeks from baseline. Patients then entered an open-label, 40 week extension trial (patients in the placebo group were randomly allocated to alogliptin 12.5 or 25 mg).. www.clinicaltrials.gov ; pivotal trial NCT01263483; Long term trial NCT01263509.. Least square mean change in HbA1c after 12 weeks' therapy from baseline (primary endpoint) was significantly greater in the alogliptin 12.5 mg (-0.96%; P < 0.0001) and 25 mg (-0.93%; P < 0.0001) groups compared with placebo (+0.06%). This was associated with statistically significant improvements in other measures of glycemic control, in particular sustained reductions in fasting plasma glucose and postprandial plasma glucose. These benefits were maintained for the duration of the 1 year study and, importantly, they were achieved without detrimental effects on tolerability/safety. In particular, there was no increase in the rate of hypoglycemia and almost no changes in mean body weight.. Addition of once daily alogliptin to voglibose monotherapy in Japanese patients with uncontrolled type 2 diabetes produced clinically significant improvements in glycemic control, and was well tolerated.

Topics: Adult; Aged; Blood Glucose; Body Weight; Diabetes Mellitus, Type 2; Dipeptidyl-Peptidase IV Inhibitors; Double-Blind Method; Drug Therapy, Combination; Female; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Inositol; Male; Middle Aged; Piperidines; Time Factors; Uracil

Mitiglinide, a rapid- and short-acting insulinotropic sulfonylurea receptor ligand, exhibits hypoglycemic action unlike other sulfonylureas. The efficacy of the combination of mitiglinide and alpha-glucosidase inhibitors for diabetic patients on hemodialysis (HD) has not been prospectively evaluated; therefore, we evaluated the efficacy and safety of mitiglinide in these patients.. We performed an open-label randomized study with 36 type 2 diabetics with poor glycemic control on HD and receiving daily doses of voglibose (0.9 mg). The patients were randomly assigned to two groups: a combination-therapy group (mitiglinide group), mitiglinide initial dose 7.5 - 15 mg titrated to 30 mg daily and constant daily dose 0.9 mg of voglibose, and a monotherapy group (control group), constant daily dose 0.9 mg of voglibose alone. The efficacy of the treatment was determined by monitoring plasma glucose, hemoglobin A1c (Hb(A1c)), and glycated albumin (GA) levels and using homeostasis model assessment of insulin resistance (HOMA-IR). Safety and tolerance were determined by monitoring clinical and laboratory parameters.. The final dose of mitiglinide was 22.9 +/- 8.9 (mean +/- s.d.) mg (0.41 mg/kg) daily. Mitiglinide reduced fasting plasma glucose and GA levels after 4 weeks and Hb(A1c) levels after 8 weeks. Triglyceride levels and HOMA-IR values also decreased significantly after mitiglinide treatment. No significant changes in blood pressure levels or serious adverse effects such as hypoglycemia or liver impairment were observed.. This study suggests a combination therapy of mitiglinide and voglibose may have potential for the treatment of diabetics on HD. Due to the small sample size used, further studies should be performed, particularly to assess the safety of mitiglinide treatment.

Topics: Aged; Diabetes Mellitus, Type 2; Female; Glycated Hemoglobin; Humans; Hyperglycemia; Hypoglycemia; Hypoglycemic Agents; Inositol; Isoindoles; Male; Renal Dialysis; Treatment Outcome

The study to assess whether voglibose could prevent type 2 diabetes developing in high-risk Japanese subjects with impaired glucose tolerance (IGT) were performed. This was a multicenter, randomised, double-blind, parallel group trial comparing voglibose 0.2 mg three times a day and corresponding placebo. 1,780 eligible subjects received standard diet and exercise therapy, and 897 were randomised to receive voglibose and 883 placebo. The study was planned for treatment to be continued until participants developed type 2 diabetes[primary endpoint; determined by bi-annual oral glucose tolerance tests (OGTTs) as well as fasting blood glucose measured every 3 months] or normalisation of the OGTT or for a minimum of 3 years, subject to the findings of an interim analysis. The interim analysis significantly favoured voglibose and this end-of-study report involves individuals treated for an average of 48.1 weeks. Subjects treated with voglibose had a significantly lower risk for the progression to type 2 diabetes than placebo (50/897 vs 106/881: hazard ratio 0.595). Also, significantly more subjects in the voglibose group achieved a normal OGTT compared with those in the placebo group (599/897 vs 454/881: hazard ratio 1.539). Voglibose, in addition to standard care with diet and exercise, was effective in preventing the progression of IGT to type 2 diabetes and in facilitating the normalisation of the OGTT in high-risk Japanese subjects with IGT.

Topics: Adult; Aged; Diabetes Mellitus, Type 2; Double-Blind Method; Female; Humans; Hypoglycemic Agents; Inositol; Male; Middle Aged; Prediabetic State

Post-prandial hyperglycemia, hyperlipidemia, and endothelial dysfunction play an important role in the pathogenesis of atherosclerosis. Improvement in post-prandial hyperglycemia on alpha-glucosidase inhibitors (alpha-GIs) is associated with a risk reduction of cardiovascular diseases, but the post-prandial effects of alpha-GIs on endothelial function and incretin secretion in type 2 diabetic patients with coronary artery disease (CAD) remain unclear.. The post-prandial effects of a single administration of miglitol and voglibose on endothelial function and changing levels of glucose, insulin, lipids, glucagon-like peptide (GLP)-1, and gastric inhibitory polypeptide (GIP) were compared after a standard meal loading in 11 diabetic patients with CAD, using a placebo-controlled cross-over design. The changing levels of glucose, insulin and triglycerides at 60 min were significantly lower in the miglitol group than in the voglibose and placebo groups (all P<0.01). GLP-1 levels were significantly higher at 120 min (P<0.05) and GIP levels were significantly lower at 30 min and 60 min (P<0.05) in the miglitol group compared to other treatments. The reactive hyperemia duration at 120 min was significantly maintained in the miglitol group compared to the other groups.. A single administration of miglitol significantly improved post-prandial glucose/lipid metabolism, incretin secretion, and endothelial dysfunction in diabetic patients with CAD, suggesting that miglitol may be a useful anti-atherogenic agent (UMIN000002264).

Topics: 1-Deoxynojirimycin; Aged; Coronary Artery Disease; Coronary Disease; Cross-Over Studies; Diabetes Mellitus, Type 2; Double-Blind Method; Endothelium, Vascular; Enzyme Inhibitors; Female; Glucose; Glycoside Hydrolase Inhibitors; Humans; Hypoglycemic Agents; Incretins; Inositol; Lipid Metabolism; Male; Middle Aged; Treatment Outcome

To compare the efficacy and safety of sitagliptin (a dipeptidyl peptidase-4 inhibitor) and voglibose (an alpha-glucosidase inhibitor) monotherapy in Japanese patients with type 2 diabetes who have inadequate glycaemic control (HbA1c > or =6.5% and <10.0%) on diet and exercise.. In a multi-center, randomized, double-blind, parallel-group study, 319 patients were randomized (1:1) to 12-week treatment with sitagliptin 50 mg once daily or voglibose 0.2 mg thrice daily before meals. The primary analysis assessed whether sitagliptin was non-inferior to voglibose in lowering HbA1c.. After 12 weeks, sitagliptin was non-inferior to voglibose for HbA1c-lowering efficacy. Furthermore, sitagliptin was superior to voglibose, providing significantly greater reductions in HbA1c from baseline [least squares mean changes in HbA1c [95% confidence intervals (CI)] = -0.7% (-0.8 to -0.6) and -0.3% (-0.4 to -0.2), respectively; between-group difference = -0.4% (-0.5 to -0.3), p < 0.001]. Sitagliptin was also superior to voglibose on other key efficacy endpoints, including change from baseline in 2-h postmeal glucose (-2.8 mmol/l vs. -1.8 mmol/l, p < 0.001) and fasting plasma glucose (-1.1 mmol/l vs. -0.5 mmol/l, p < 0.001). After 12 weeks, the incidences of clinical adverse experiences (AEs), drug-related AEs and gastrointestinal AEs in the sitagliptin group (48.5, 10.4 and 18.4%, respectively) were significantly (p < 0.05) lower than those in the voglibose group (64.7, 26.3 and 34.6%, respectively). The incidences of hypoglycaemia, serious AEs and discontinuations due to AEs were low and similar in both groups.. In Japanese patients with type 2 diabetes, once-daily sitagliptin monotherapy showed greater efficacy and better tolerability than thrice-daily voglibose over 12 weeks.

Topics: Asian People; Diabetes Mellitus, Type 2; Dipeptidyl-Peptidase IV Inhibitors; Double-Blind Method; Drug Administration Schedule; Female; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Inositol; Male; Middle Aged; Pyrazines; Sitagliptin Phosphate; Treatment Outcome; Triazoles

To confirm the efficacy of vildagliptin in patients with type 2 diabetes (T2D) by testing the hypothesis that glycosylated haemoglobin (HbA1c) reduction with vildagliptin is superior to that with voglibose after 12 weeks of treatment.. In this 12-week, randomized, double-blind, active-controlled, parallel-group study, the efficacy and safety of vildagliptin (50 mg bid, n = 188) was compared with that of voglibose (0.2 mg tid, n = 192) in patients with T2D who were inadequately controlled with diet and exercise.. The characteristics of two groups were well matched at baseline. The mean age, body mass index (BMI) and HbA1c were 59.1 years, 24.9 kg/m(2) and 7.6%, respectively. At baseline, fasting plasma glucose (FPG) and 2-h postprandial glucose (PPG) were 9.01 mmol/l (162.2 mg/dl) and 13.57 mmol/l (244.3 mg/dl), respectively. The adjusted mean change in HbA1c from baseline to endpoint was -0.95 +/- 0.04% in the vildagliptin-treated patients and -0.38 +/- 0.04% in those receiving voglibose (between-group change = 0.57 +/- 0.06%, 95% confidence interval (CI) (-0.68 to -0.46%), p < 0.001), showing that vildagliptin was superior to voglibose. Endpoint HbA1c < or = 6.5% was achieved in 51% vildagliptin-treated patients compared with 24% patients who were on voglibose (p < 0.001). Vildagliptin also exhibited significantly (p < 0.001) greater reduction compared with voglibose in both FPG [1.34 vs. 0.43 mmol/l (24.1 vs. 7.8 mg/dl)] and 2-h PPG [2.86 vs. 1.1 mmol/l (51.5 vs. 19.8 mg/dl)]. Overall adverse events (AEs) were lower in the vildagliptin-treated patients compared with that in the voglibose-treated patients (61.2 vs. 71.4%), with no incidence of hypoglycaemia and serious adverse events with vildagliptin. Gastrointestinal AEs were significantly lower with vildagliptin compared with that of the voglibose (18.6 vs. 32.8%; p = 0.002).. Vildagliptin (50 mg bid) showed superior efficacy and better tolerability compared with voglibose in Japanese patients with T2D.

Topics: Adamantane; Asian People; Diabetes Mellitus, Type 2; Dipeptidyl-Peptidase IV Inhibitors; Double-Blind Method; Female; Humans; Hypoglycemic Agents; Inositol; Male; Middle Aged; Nitriles; Postprandial Period; Pyrrolidines; Treatment Outcome; Vildagliptin

The increased prevalence of type 2 diabetes mellitus is a major concern for health providers. We therefore assessed whether voglibose, an alpha-glucosidase inhibitor, could prevent the development of type 2 diabetes in high-risk Japanese individuals with impaired glucose tolerance.. 1780 eligible patients on a standard diet and taking regular exercise with impaired glucose tolerance were randomly assigned to oral voglibose 0.2 mg three times a day (n=897) or placebo (n=883) in a multicentre, double-blind, parallel group trial. Treatment was continued until participants developed type 2 diabetes (primary endpoint) or normoglycaemia (secondary endpoint), or for a minimum of 3 years, subject to the findings of an interim analysis. Analysis was by full analysis set. This trial is registered with the University Hospital Medical Information Network (UMIN) clinical trials registry, number UMIN 000001109.. In the interim analysis, voglibose was better than placebo (p=0.0026) in individuals treated for an average of 48.1 weeks (SD 36.3). Patients treated with voglibose had a lower risk of progression to type 2 diabetes than did those on placebo (50 of 897 vs 106 of 881; hazard ratio 0.595, 95% CI 0.433-0.818; p=0.0014). More people in the voglibose group achieved normoglycaemia than did those in the placebo group (599 of 897 vs 454 of 881; 1.539, 1.357-1.746; p<0.0001). 810 (90%) of 897 patients in the voglibose group had adverse events versus 750 (85%) of 881 in the placebo group. Serious adverse events (all one each) in the voglibose group were cholecystitis, colonic polyp, rectal neoplasm, inguinal hernia, liver dysfunction, and subarachnoid haemorrhage, and in the placebo group were cerebral infarction and cholecystitis.. Voglibose, in addition to lifestyle modification, can reduce the development of type 2 diabetes in high-risk Japanese individuals with impaired glucose tolerance.. Takeda.

Topics: Administration, Oral; Analysis of Variance; Diabetes Mellitus, Type 2; Disease Progression; Double-Blind Method; Female; Glucose Intolerance; Glycoside Hydrolase Inhibitors; Humans; Hypoglycemic Agents; Incidence; Inositol; Japan; Kaplan-Meier Estimate; Life Style; Male; Middle Aged; Prevalence; Proportional Hazards Models; Risk Assessment; Risk Reduction Behavior; Severity of Illness Index

Many patients with diabetes mellitus (DM) require a combination of antidiabetic drugs with complementary mechanisms of action to lower their hemoglobin A1c levels to achieve therapeutic targets and reduce the risk of cardiovascular complications. Linagliptin is a novel member of the dipeptidyl peptidase-4 (DPP-4) inhibitor class of antidiabetic drugs. DPP-4 inhibitors increase incretin (glucagon-like peptide-1 and gastric inhibitory polypeptide) levels, inhibit glucagon release and, more importantly, increase insulin secretion and inhibit gastric emptying. Currently, phase III clinical studies with linagliptin are underway to evaluate its clinical efficacy and safety. Linagliptin is expected to be one of the most appropriate therapies for Japanese patients with DM, as deficient insulin secretion is a greater concern than insulin resistance in this population. The number of patients with DM in Japan is increasing and this trend is predicted to continue. Several antidiabetic drugs are currently marketed in Japan; however there is no information describing the effective dose of linagliptin for Japanese patients with DM.. This prospective, randomized, double-blind study will compare linagliptin with placebo over a 12-week period. The study has also been designed to evaluate the safety and efficacy of linagliptin by comparing it with another antidiabetic, voglibose, over a 26-week treatment period. Four treatment groups have been established for these comparisons. A phase IIb/III combined study design has been utilized for this purpose and the approach for calculating sample size is described.. This is the first phase IIb/III study to examine the long-term safety and efficacy of linagliptin in diabetes patients in the Japanese population.

Topics: Data Interpretation, Statistical; Diabetes Mellitus, Type 2; Dipeptidyl-Peptidase IV Inhibitors; Double-Blind Method; Humans; Hypoglycemic Agents; Inositol; Placebos; Prospective Studies; Research Design; Sample Size

The detrimental effects of a sedentary lifestyle and poor dietary habits are having a significant negative impact on health statistics, with obesity and its attendant risks becoming a major problem in most developed nations, including Japan. Interventions which prevent or delay the development of type 2 diabetes have the potential to reduce the morbidity and mortality associated with the disease and, as a consequence, related healthcare costs. The study conducted to assess whether alpha-glucosidase inhibitor, voglibose could prevent type 2 diabetes developing in high-risk Japanese subjects with impaired glucose tolerance (IGT). 1,780 eligible subjects received standard diet and exercise therapy, and 897 were randomised to receive voglibose and 883 placebo. The study was planned for treatment to be continued until participants developed type 2 diabetes [primary endpoint; determined by bi-annual oral glucose tolerance tests (OG'Ts) as well as fasting blood glucose measured every 3 months] or normoglycaemia or for a minimum of 3 years, subject to the findings of an interim analysis. The interim analysis significantly favoured voglibose and end-of-study report involves individuals treated for an average of 48.1 weeks. Subjects treated with voglibose had a significantly lower risk for the progression to type 2 diabetes than placebo (50/897 vs 106/881: hazard ratio 0.595). Also, significantly more subjects in the voglibose group achieved normoglycaemia compared with those in the placebo group (599/897 vs 454/881: hazard ratio 1.539). Voglibose, in addition to standard care with diet and exercise, was effective in preventing the progression of IGT to type 2 diabetes and in increasing the proportion of individuals with normoglycaemia in high-risk Japanese subjects with IGT.

Topics: Asian People; Cardiovascular Diseases; Diabetes Mellitus, Type 2; Disease Progression; Enzyme Inhibitors; Female; Glucose Intolerance; Glucose Tolerance Test; Glycoside Hydrolase Inhibitors; Humans; Hypoglycemic Agents; Inositol; Life Style; Male; Middle Aged; Risk

Topics: Diabetes Mellitus, Type 2; Female; Humans; Hypoglycemic Agents; Inositol; Male; Middle Aged; Pioglitazone; Thiazolidinediones; Treatment Outcome; Weight Gain

We aimed to determine the feasibility of substituting thiazolidinedione-based therapy for insulin injection therapy in patients with type 2 diabetes.. Thirty-six subjects (17 men and 19 women) aged 67.8 +/- 11.3 years with an average insulin dose of 0.46 +/- 0.17 U/kg bodyweight, a duration of insulin therapy of 6.1 +/- 8.2 years and an average hemoglobin A1c (HbA1c) of 6.8 +/- 1.3% were switched from insulin injection therapy to pioglitazone, glimepiride and voglibose combination therapy.. The number of subjects achieving HbA1c levels of less than 7% at 4 months was 30. The success rate of switch therapy was 83% (30/36). HbA1c was significantly reduced from 6.7 +/- 1.3% to 5.9 +/- 0.7% at 4 months after the switch (P < 0.01) in 32 patients who completed the planned 4-month study. No adverse effects including heart failure, liver dysfunction or severe hypoglycemia were observed. The insulin dose and the maximum blood glucose on the switch day were significantly lower and the age was significantly higher in the subjects who achieved HbA1c less than 7% at 4 months compared to those who did not (P < 0.05).. Thiazolidinedione-based oral combination therapy may efficiently and safely substitute relatively high-dose insulin injection therapy in patients with type 2 diabetes.

Topics: Administration, Oral; Aged; Diabetes Mellitus, Type 2; Drug Therapy, Combination; Female; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Inositol; Insulin; Male; Middle Aged; Pioglitazone; Sulfonylurea Compounds; Thiazolidinediones; Treatment Outcome

To investigate short-term effects of pioglitazone and voglibose on serum concentrations of both total and high-molecular-weight (HMW) adiponectin measured with a novel sandwich enzyme-linked immunosorbent assay (ELISA) ,and on plasma fibrinolysis indicators, in Type 2 diabetic patients with inadequate glycaemic control on sulphonylureas.. Thirty-four diabetic patients were randomized to receive pioglitazone or voglibose treatment for 12 weeks, after which serum HMW adiponectin was measured. Plasma plasminogen activator inhibitor (PAI) 1 and thrombin-activatable fibrinolysis inhibitor (TAFI), a recently identified inhibitor of fibrinolysis, were measured as fibrinolysis inhibitors.. At baseline, serum HMW adiponectin correlated negatively with plasma TAFI in all patients with Type 2 diabetes (r = -0.367, P = 0.0423). Both groups showed similar improvements in glycaemic control. Serum total and HMW adiponectin increased in patients treated with pioglitazone, but did not change in patients treated with voglibose. The HMW : total adiponectin ratio increased significantly after treatment with pioglitazone (P = 0.0004). The change in HbA(1c) correlated negatively with changes in serum HMW adiponectin in patients treated with pioglitazone (r = -0.694, P = 0.0034). Plasma PAI-1 and TAFI did not change with pioglitazone treatment.. Increased serum HMW adiponectin may contribute to the improvement in glycaemic control after pioglitazone treatment. Plasma PAI-1 and TAFI were unchanged by either drug.

Topics: Adiponectin; Blood Glucose; Body Mass Index; Diabetes Mellitus, Type 2; Enzyme-Linked Immunosorbent Assay; Female; Humans; Hypoglycemic Agents; Inositol; Insulin Resistance; Male; Molecular Weight; Pioglitazone; Plasminogen Activator Inhibitor 1; Thiazolidinediones; Treatment Outcome

Unfortunately, clinicians are diagnosing a growing number of patients on hemodialysis (HD) with insulin-resistant, Type 2 diabetes in Japan. While alpha-glucosidase inhibitors (alpha-GI) such as oral antidiabetic agents are indicated for Japanese diabetics on HD, pioglitazone and other PPARgamma agonists are now contraindicated. No prospective study has evaluated the use of thiazolidinediones in diabetics with end-stage renal disease (ESRD) in combination with alpha-GI. In this study we evaluated the efficacy and safety of pioglitazone in Japanese diabetics on HD.. An open-label randomized study was performed on 31 Type 2 diabetics on HD with unstable glycemic control receiving constant doses of voglibose. The patients were randomly assigned to two groups: a combination therapy group (pioglitazone group) administered pioglitazone (fixed dose 30 mg) plus voglibose, and a monotherapy group (control group) administered voglibose alone. The efficacy of the treatments was determined by monitoring glycemic control (plasma glucose and HbA1c) and insulin resistance. Insulin resistance was assessed using the homeostasis model assessment for insulin resistance (HOMA-R). Safety and tolerance were determined by monitoring clinical and laboratory parameters.. The pioglitazone was effective in reducing plasma glucose and HbA1c from the baseline levels from Week 4 onward. It was also effective in reducing triglycerides. HOMA-R decreased significantly at 4 weeks in the pioglitazone group, and the decrease continued up to the last measurement at Week 12. Systolic and diastolic blood pressures at 4 weeks were statistically lower in the pioglitazone group than in the control group. No serious adverse effects such as hypoglycemia, liver impairment or rhabdomyolysis were observed in any of the patients.. Pioglitazone was safe and effective as a treatment for diabetics on dialysis therapy. The 30 mg daily dose of pioglitazone was sufficient for Japanese HD patients, obese and nonobese alike. The combination therapy of pioglitazone with voglibose will add to the list of first-line drug treatments for glycemic control in uremic Type 2 diabetes.

Topics: Aged; Asian People; Blood Glucose; Case-Control Studies; Demography; Diabetes Mellitus, Type 2; Drug Therapy, Combination; Drug-Related Side Effects and Adverse Reactions; Female; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Inositol; Insulin Resistance; Japan; Lipids; Male; Pioglitazone; Renal Dialysis; Thiazolidinediones

Adipocytokines are involved in the development of insulin resistance and endothelial dysfunction in diabetic patients. However, the relationship between these factors remains unclear. We observed a chronological change in circulating adipocytokines and blood pressure levels with administration of oral hypoglycaemic agents in Type 2 diabetic (T2DM) subjects.. Thirty poorly controlled T2DM subjects (aged 60.1 +/- 1.5 years, 11 males and 19 females) were randomized into two groups: voglibose (initial dose 0.6 mg/day, increased to 0.9 mg/day) and pioglitazone (initial dose 15 mg/day, increased to 30 mg/day).. Both treatment groups showed a similar improvement in glycaemic control. In pioglitazone-treated patients, circulating adiponectin levels were significantly increased from 4 weeks after the start of treatment, and until the end of the study at 12 weeks. Plasma tumour necrosis factor-alpha (TNF-alpha) levels were significantly decreased only at 12 weeks. In contrast, no significant changes in plasma adiponectin or TNF-alpha levels were observed in voglibose-treated patients. Plasma PAI-1 and leptin levels were not significantly changed at 12 weeks in either treatment group. Pioglitazone significantly decreased systolic and diastolic blood pressure levels at 12 weeks, but voglibose had no effect.. In summary, pioglitazone caused an immediate increase in circulating adiponectin levels, followed by a reduction of TNF-alpha. The observed increase in circulating adiponectin could be related to decreases in both systolic and diastolic blood pressure.

Topics: Adiponectin; Administration, Oral; Blood Glucose; Blood Pressure; Diabetes Mellitus, Type 2; Female; Humans; Hypoglycemic Agents; Inositol; Leptin; Male; Middle Aged; Pioglitazone; Plasminogen Activator Inhibitor 1; Thiazolidinediones; Tumor Necrosis Factor-alpha

An open-label prospective cross-over trial was performed to compare the efficacy and adverse effects of nateglinide with those of voglibose on Japanese early type 2 diabetes (who were oral hypoglycemic agent naïve and whose HbA(1C) levels were between 7.0 and 7.9% before treatment). Fourteen patients received 270 mg/day of nateglinide and 15 patients received 0.6 mg/day of voglibose. After 12 weeks of either therapy, the drugs were switched and treatment was continued for another 12 weeks. After 3-month treatment with each drug, HbA(1C) value decreased significantly (baseline HbA(1C) 7.24 +/- 0.42%, 6.70 +/- 0.47% with nateglinide: p<0.01, 6.93 +/- 0.62% with voglibose: p<0.05) but the difference in the effect between nateglinide and voglibose was not significant (p = 0.121). Symptoms related to hypoglycemia (e.g., increased appetite, palpitation, sweating, tremor) were scarcely observed with either voglibose or nateglinide treatments. Abdominal fullness/borborygmi was frequently reported, with variable severity, by patients on voglibose but this was absent or mild in those on nateglinide. After completion of both arms of the study, more patients favored nateglinide than voglibose. Our results suggest that nateglinide is an effective and safe drug in the treatment of early type 2 diabetes, similar to voglibose.

Topics: Aged; alpha-Glucosidases; Appetite; Body Weight; Cross-Over Studies; Cyclohexanes; Diabetes Mellitus, Type 2; Drug-Related Side Effects and Adverse Reactions; Female; Follow-Up Studies; Gastrointestinal Tract; Glycated Hemoglobin; Humans; Hypoglycemia; Inositol; Lipids; Liver Function Tests; Male; Middle Aged; Nateglinide; Phenylalanine; Treatment Outcome

Postprandial hyperglycemia and hyperlipidemia are considered risk factors for cardiovascular disease. This study was designed to elucidate whether improving the postprandial state by voglibose, an alpha-glucosidase inhibitor, leads to the reduction of oxidative stress markers and soluble adhesion molecules in obese type 2 diabetic patients. A total of 30 Japanese obese type 2 diabetic patients were randomly assigned and treated for 3 weeks with either diet alone (the control group) or diet plus voglibose (0.9 mg daily) (the voglibose group) (n=15 each). Analysis of the diurnal metabolic profiles revealed a significant reduction of postprandial hyperglycemia and hyperlipidemia in the voglibose group relative to the control group (P<.05), despite the similar improvement in body mass index and hemoglobin A(1c) in both groups. Voglibose also decreased significantly the plasma levels of soluble intercellular adhesion molecule 1 and urinary excretion of 8-iso-prostaglandin F(2)alpha and 8-hydroxydeoxyguanosine (P<.01) and C-reactive protein (P<.05) relative to the control group. In conclusion, this study represents the first demonstration that voglibose reduces oxidative stress generation and soluble intercellular adhesion molecule 1 in parallel with the reduction of postprandial hyperglycemia and hyperlipidemia in obese type 2 diabetic patients.

Topics: Adult; Biomarkers; Diabetes Mellitus, Type 2; Female; Glycoside Hydrolase Inhibitors; Humans; Hyperglycemia; Hyperlipidemias; Hypoglycemic Agents; Inositol; Intercellular Adhesion Molecule-1; Japan; Male; Middle Aged; Obesity; Oxidative Stress; Single-Blind Method; Solubility

An open randomized prospective study was performed to elucidate the effect of an alpha-glucosidase inhibitor, voglibose, on the progression of atherosclerosis in subjects with type 2 diabetes.. Voglibose at a dose of 0.4-0.6 mg/day was added on 51 subjects out of 101 type 2 diabetic patients being treated with diet, sulphonylurea (SU) or insulin injections, and the average (AveIMT) and maximum intima-media thickness (MaxIMT) of their carotid arteries were examined for 3 years.. Irrespective of the differences in treatments, addition of voglibose reduced the progression of AveIMT and MaxIMT to -0.024 +/- 0.047 (+/-S.D.) and -0.021 +/- 0.144 mm/year, respectively. Without voglibose, diabetic patients showed significant (P < 0.0001) progression of AveIMT and MaxIMT (0.056 +/- 0.046 and 0.098 +/- 0.122 mm/year, respectively). The administration of voglibose resulted in a significant reduction of hemoglobin A1c (HbA1c), total cholesterol and triglyceride concentrations, as well as an increase in HDL cholesterol concentration. Multivariate regression analysis showed that administration of voglibose independently reduced the progression of AveIMT by 0.069 mm/year (P < 0.0001).. These results suggest that voglibose reduces the progression of IMT and may be a candidate for an anti-atherosclerotic drug for type 2 diabetic patients.

Topics: Analysis of Variance; Carotid Arteries; Diabetes Mellitus, Type 2; Female; Glycated Hemoglobin; Glycoside Hydrolase Inhibitors; Humans; Hypoglycemic Agents; Inositol; Insulin; Male; Middle Aged; Patient Selection; Regression Analysis; Tunica Intima; Tunica Media; Ultrasonography

Atherosclerosis is the major cause of morbidity and mortality in patients with type 2 diabetes, and pioglitazone has been reported to have anti-inflammatory and potential antiatherogenic effects. The aim of the present study was to determine whether pioglitazone, glibenclamide, or voglibose affects carotid intima-media thickness (IMT), pulse wave velocity (PWV), and urinary albumin excretion (UAE) in normotensive type 2 diabetic nephropathy patients. Forty-five normotensive type 2 diabetes patients with microalbuminuria were randomized to 12-month treatment with pioglitazone (30 mg/d, n = 15), glibenclamide (5 mg/d, n = 15), or voglibose (0.6 mg/d, n = 15). Pre- and posttreatment UAE, PWV, and IMT values were compared between treatment groups and a group of age-matched healthy control subjects (n = 30). Pretreatment PWV, IMT, and UAE values differed little between the 3 groups, but UAE was greater in the 45 type 2 diabetes patients (132.5 +/- 36.4 microg/min) than in the control subjects (6.2 +/- 1.8 microg/min, P < .001). IMT (0.76 +/- 0.12 mm) was significantly greater in the diabetics than in the controls (0.60 +/- 0.08 mm, P < .01). PWV (1,840 +/- 320 cm/s) was also significantly greater in the diabetics than in the controls (1,350 +/- 225 cm/s, P < .01). After 6 and 12 months, UAE, IMT, and PWV in the pioglitazone treatment group were significantly lower than those in the glibenclamide treatment group and voglibose treatment group (UAE: 6 months, P < .05 and 12 months, P < .01; IMT and PWV: 6 months, P < .05 and 12 months, P < .05). Pioglitazone, but not glibenclamide or voglibose, appears to be effective in reducing UAE, IMT, and PWV in normotensive type 2 diabetes patients with microalbuminuria.

Topics: Albuminuria; Blood Pressure; Blood Urea Nitrogen; Carotid Arteries; Creatinine; Diabetes Mellitus, Type 2; Double-Blind Method; Enzyme Inhibitors; Female; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Inositol; Male; Middle Aged; Pioglitazone; Protein Precursors; Sulfonylurea Compounds; Thiazolidinediones

The aim of this study was to investigate whether combination therapy of alpha-glucosidase inhibitor and a sulfonylurea (SU) drug can prolong the duration of good glycemic control compared with SU alone in patients with type 2 diabetes. The open prospective study included 124 Japanese patients with type 2 diabetes and inadequate glycemic control (hemoglobin A(1c) [HbA(1c)] gt; 7.0%). Patients were given either voglibose plus a SU compound (glibenclamide or gliclazide, n = 61) or SU drug alone (n = 63). The first 6-month run-in period (targeted to HbA(1c) /= 8.0%). Fifty patients on combination therapy and 48 patients on SU alone completed the trial. During the follow-up, 21 patients on combination therapy and 30 patients on SU alone showed deterioration of glycemic control and reached the endpoint (P =.04). The combination therapy significantly prolonged the duration of good glycemic control (HbA(1c) < 8.0%) compared with SU alone by Kaplan-Meier estimated survival analysis using a log-rank test (P =.02). Thus, combination therapy with voglibose and a SU agent prolongs the duration of good glycemic control compared with SU alone in patients with type 2 diabetes.

Topics: Blood Glucose; Diabetes Mellitus, Type 2; Drug Therapy, Combination; Enzyme Inhibitors; Female; Gliclazide; Glyburide; Glycated Hemoglobin; Glycoside Hydrolase Inhibitors; Humans; Inositol; Male; Middle Aged; Sulfonylurea Compounds; Survival Analysis; Time Factors

We performed a randomized crossover open comparative study to evaluate the efficacy and safety of voglibose and acarbose in 30 patients with type 2 diabetes who were not well controlled with diet therapy. There was no significant reduction of FBG with either voglibose or acarbose at 4 and 8 weeks after treatment. The 1 h postprandial blood glucose (PPBG) level was significantly decreased from 224.9+/-42.8 to 204.1+/-37.6 (P=0.005) and 206.1+/-38.9 mg/dl (P=0.038) after voglibose therapy at 4 and 8 weeks, respectively. Significant decrease was also obtained after acarbose treatment from 228.3+/-37.4 to 182.7+/-35.5 (P<0.001) and 186.6+/-36.1 mg/dl (P<0.001). The decrease of 1 h PPBG was associated with a significant fall of serum insulin concentration. HbA(1c) levels were also significantly decreased from 7.07+/-1.21 to 6.83+/-1.11 (P=0.017) and 6.79+/-1.33% (P=0.036) after voglibose and 6.98+/-0.98 to 6.70+/-1.04 (P<0.001) and 6.59+/-1.04% (P<0.001) after acarbose at 4 and 8 weeks. In contrast to voglibose, treatment with acarbose significantly decreased the 2 h PPBG at 4 and 8 weeks and the 2 h postprandial serum insulin concentration at 8 weeks. Adverse drug events were more commonly reported in acarbose-treated patients (P<0.05). Increased flatulence was observed in 56.7 and 90% of the patients taking voglibose and acarbose, respectively, while abdominal distention was noted in 10 and 16.7%. Significantly decreased body weights of 0.9 and 0.8 kg were recorded at 8 weeks after voglibose and acarbose therapy, respectively. We conclude that both voglibose (0.2 mg) and acarbose (100 mg) thrice daily significantly decreased HbA(1c), PPBG and postprandial insulin levels. At these dose levels, voglibose was associated with less gastrointestinal side effects and slightly less efficacy for postprandial glucose reduction.

Topics: Acarbose; Adult; Aged; Blood Glucose; Cross-Over Studies; Diabetes Mellitus, Type 2; Enzyme Inhibitors; Female; Food; Glycated Hemoglobin; Glycoside Hydrolase Inhibitors; Humans; Hypoglycemic Agents; Inositol; Insulin; Male; Middle Aged

OBJECTIVE; To examine the effects of diet and diet with voglibose or glyburide on abdominal adiposity and metabolic abnormalities in patients with type 2 diabetes.. A total of 36 Japanese patients with newly diagnosed type 2 diabetes (50.8 +/- 8.6 years of age, BMI 24.5 +/- 3.5 kg/m(2)) and 273 normal control subjects were studied. The patients were treated for 3 months with diet alone (30 kcal/kg per day) (n = 15), diet with voglibose (n = 12), or diet with glyburide (n = 9). They underwent 75-g oral glucose tolerance testing, assessment of insulin sensitivity (SI), and acute insulin response (AIR) with intravenous glucose tolerance testing based on the minimal model, and measurement of abdominal visceral adipose tissue area (VAT) and subcutaneous adipose tissue area (SAT) by computed tomography before and after treatment.. The diabetic patients had comparable SAT but larger VAT than the control subjects. With a mean weight loss of 2-3 kg, VAT and SAT were decreased similarly in all treatment groups. The VAT-to-SAT ratio was decreased only in the voglibose group. Glycemic control and serum lipid profiles were improved in all groups. Changes in glycemic control after diet were closely correlated with changes in VAT but not with changes in SAT. SI and AIR were unchanged in the diet group but were improved in the voglibose and glyburide groups.. In Japanese patients with newly diagnosed type 2 diabetes who were relatively lean but had excess VAT, diet with or without voglibose or glyburide effectively reduced VAT. Decrease in VAT was closely associated with improvement of glycemic control with diet. Additional use of voglibose or low-dose glyburide had no detrimental effects on abdominal adiposity and had beneficial effects on SI and AIR.

Topics: Abdomen; Adipose Tissue; Adult; Blood Glucose; Body Mass Index; Body Weight; Cholesterol; Cholesterol, HDL; Diabetes Mellitus, Type 2; Diet, Diabetic; Energy Intake; Fasting; Fatty Acids, Nonesterified; Female; Glucose Tolerance Test; Glyburide; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Inositol; Insulin; Male; Triglycerides

In this study, we characterized type 2 diabetic patients responding well to the alpha-glucosidase inhibitor voglibose administration as an adjunct to sulfonylurea treatment. Thirty-three type 2 diabetic patients were enrolled in an open prospective study. All the patients had been treated for at least 1 year with a sulfonylurea drug, in whom HbA1c level had been stable for at least 12 weeks. The patients were given voglibose at a dose of 0.2 mg t.i.d. for 12 weeks. Voglibose administration significantly decreased the mean HbA1c level in all the patients at 4, 8, and 12 weeks. Twelve (36%) of the study patients were responders, when the responders were defined as patients whose HbA1c level at 12 weeks fell by at least 1.0% from baseline, or those whose HbA1c level at 12 weeks was < or =7.0%, falling by at least 0.5% from baseline. The baseline fasting plasma glucose (FPG) was significantly lower, and the baseline homeostasis model assessment (HOMA) beta-cell function (HOMA-%beta) was significantly higher in the responders than in the non-responders. There were more patients who had FPG <170 mg/dl and/or HOMA-%beta > or =30% in the responders than in the non-responders (P<0.005). None of the patients with both FPG > or =170 mg/dl and HOMA-%beta >30% responded to the adjunct treatment. These results indicate that baseline FPG and HOMA-%beta are useful clinical markers to predict the effectiveness of the adjunct therapy of voglibose in sulfonylurea-treated type 2 diabetic patients.

Topics: Administration, Oral; Adult; Aged; Blood Glucose; Diabetes Mellitus, Type 2; Drug Administration Schedule; Drug Therapy, Combination; Enzyme Inhibitors; Female; Glycated Hemoglobin; Glycoside Hydrolase Inhibitors; Humans; Hypoglycemic Agents; Inositol; Male; Middle Aged; Sulfonylurea Compounds; Time Factors

To investigate the effects of voglibose, an alpha-glucosidase inhibitor, on daily glycemic excursions, insulin secretion, and insulin sensitivity in non-insulin-treated NIDDM patients.. An open prospective study was conducted in 27 NIDDM patients receiving diet therapy alone or treatment with a sulfonylurea drug. Of the study subjects, 14 patients were treated with voglibose; the remaining 13 patients served as the control group. The metabolic parameters were evaluated before treatment and at week 4 of treatment as follows: glycemic excursions by M-value and 1,5-anhydro-D-glucitol (1,5-AG), insulin secretion by area under the curve of daily serum insulin (AUCinsulin), and insulin sensitivity by the K index of the insulin tolerance test (KITT).. After the study treatment, HbA1c and plasma glucose in the patients who had received voglibose were comparable to those of patients in the control group. M-value was lower in the patients treated with voglibose than in the control subjects (5.7 +/- 0.9 vs. 9.8 +/- 1.2, P < 0.05). 1,5-AG was higher in the patients treated with voglibose than in the control subjects (12.2 +/- 1.0 vs. 8.2 +/- 0.7 micrograms/ml, P < 0.01). A statistically significant increase in AUCinsulin occurred after treatment with voglibose (2,223.5 +/- 390.6 to 1,546.7 +/- 303.4 pmol.l-1.h, P < 0.05), but no change occurred in the control group (2,364.5 +/- 315.4 to 2,464.2 +/- 269.3 pmol.l-1.h, P = 0.60). Insulin sensitivity (KITT) was improved to a statistically significant level in both the patients treated with voglibose and the patients in the control group. KITT in the patients after voglibose treatment was comparable to that of the control group (3.18 +/- 0.30 vs. 3.21 +/- 0.23%/min, P = 0.94).. The results suggest that voglibose lowers the daily glycemic excursions and inhibits overwork of the pancreatic beta-cells but has little effect on insulin sensitivity in NIDDM patients.

Topics: Blood Glucose; Cholesterol; Cholesterol, HDL; Data Interpretation, Statistical; Diabetes Mellitus, Type 2; Enzyme Inhibitors; Fatty Acids, Nonesterified; Female; Glycated Hemoglobin; Glycoside Hydrolase Inhibitors; Humans; Inositol; Insulin; Insulin Resistance; Insulin Secretion; Male; Middle Aged; Triglycerides

The purpose of the study was to examine the relationship between gastric emptying and the efficacy of an alpha-glucosidase inhibitor in NIDDM patients.. Sixteen NIDDM patients (4 patients treated with diet therapy alone and 12 receiving a sulfonylurea) were given 0.6 mg of voglibose daily for 4 weeks. The efficacy of voglibose was assessed by measurement of HbA1c, fasting plasma glucose, and 45- and 120-min postprandial plasma glucose (PPG) and serum insulin concentrations before and after the 4 weeks of voglibose therapy. Gastric emptying was evaluated using the proportional cumulative area under the absorption curve (% AUC) of plasma acetaminophen concentration at 60 min after ingestion of a liquid test meal containing 20 mg/kg of acetaminophen. These measurements were also taken before and after the therapy.. The change in the 45-min PPG levels from the fasting state correlated significantly with the % AUC of the plasma acetaminophen concentrations (r = 0.625, P = 0.0096) before the voglibose administrations. The mean 45-min and 2-h PPG levels were reduced significantly after 4 weeks of voglibose (P < 0.05 and P < 0.01, respectively). Two-hour postprandial serum insulin concentrations were also significantly reduced at the end of the treatment period (P < 0.05). The changes in the PPG levels between pre- and posttreatment periods correlated significantly with the % AUC of the plasma acetaminophen concentrations before the treatment period (r = 0.499, P = 0.0490; r = 0.713, P = 0.0019, respectively). There was no significant difference in the plasma acetaminophen concentrations between pre- and posttreatment periods.. The rate of gastric emptying affects the efficacy of voglibose therapy in NIDDM patients. Voglibose did not however alter the rate of gastric emptying.

Topics: Acetaminophen; Blood Glucose; Diabetes Mellitus, Type 2; Enzyme Inhibitors; Female; Gastric Emptying; Glycoside Hydrolase Inhibitors; Humans; Inositol; Insulin; Male; Metabolic Clearance Rate; Middle Aged; Postprandial Period; Regression Analysis

The alpha-glucosidase inhibitor voglibose (AO-128) was designed to prevent rapid postprandial blood glucose rises in non-insulin-dependent diabetics. We analyzed its effect on the entero-insular axis in 72 healthy volunteers in a double-blind study design before, after the 1st dose, and on the 7th day of a 7-day treatment protocol (3 daily loads). Six parallel groups of 12 volunteers received voglibose (0.5, 1.0, 2.0, or 5.0 mg) or placebo (two groups). Blood was drawn at regular intervals up to 180 min after a standardized breakfast to analyze the levels of glucose, insulin, C peptide, gastric inhibitory polypeptide, and glucagon-like peptide 1 (GLP-1). As expected, after ingestion of voglibose, slight to moderate gastro-intestinal discomfort but no severe side-effects were reported. In a dose-dependent manner, voglibose significantly reduced postprandial increases of blood glucose, insulin, and C peptide. At the lower loads (0.5 and 1 mg voglibose three times daily), these effects were more pronounced after 7 days. The postprandial increase of gastric inhibitory polypeptide was already reduced after the first load of 2 and 5 mg voglibose. In comparison to the placebo group, this inhibition became also significant for the lower loads after 7 days. Interestingly, GLP-1, originating from the lower intestines, was increasingly released under voglibose treatment. The first administration of 1 mg voglibose enhanced GLP-1 secretion > 80% above controls. Treatment with 1 mg voglibose three times daily over 7 days revealed a maximal mobilizing effect on endogenous GLP-1 (> 90% above controls) which was not further increased by 2- or 5-mg loads. We conclude that voglibose treatment effectively inhibits intestinal disaccharidases and thereby mobilizes the endogenous pool of insulinotropic GLP-1.

Topics: Adolescent; Adult; Blood Glucose; C-Peptide; Cyclohexanols; Diabetes Mellitus, Type 2; Dose-Response Relationship, Drug; Double-Blind Method; Enzyme Inhibitors; Gastric Inhibitory Polypeptide; Glucagon; Glucagon-Like Peptide 1; Glycoside Hydrolase Inhibitors; Humans; Insulin; Male; Peptide Fragments; Protein Precursors

α-Glucosidase inhibitors (AGIs) are oral antidiabetic drugs used in the treatment of type Ⅱ diabetes. It is integral to establish methods for AGIs screening. For the detection of α-glucosidase (α-Glu) activity and screening of AGIs, a chemiluminescence (CL) platform was established based on cascade enzymatic reactions. Firstly, the catalytic activity of a two-dimensional (2D) metal-organic framework (MOF) with iron as central metal atoms and 1,3,5-benzene tricarboxylic acid as a ligand (denoted as 2D Fe-BTC) in the luminol-hydrogen peroxide (H

Topics: Acarbose; alpha-Glucosidases; Catalysis; Diabetes Mellitus, Type 2; Glucose; Glycoside Hydrolase Inhibitors; Humans; Hydrogen Peroxide; Limit of Detection; Luminescent Measurements; Luminol; Metal-Organic Frameworks

Topics: Acarbose; Cardiovascular Diseases; Diabetes Mellitus, Type 2; Humans; Hypoglycemic Agents; Metformin; Public Health

Voglibose is an α-glycosidase inhibitor that improves postprandial hyperglycemia and increases glucagon-like peptide-1 (GLP-1) secretion in patients with type 2 diabetes. Recently, there has been increasing interest in the anti-inflammatory effects of voglibose on the intestine, but the underlying mechanism is not clear. This study evaluated the effects and mechanisms of voglibose on glycemic control and intestinal inflammation. Type 2 diabetic KKAy mice were treated with voglibose (1 mg/kg) by oral gavage once daily. After 8 weeks, glucose metabolism, levels of short-chain fatty acids (SCFAs), systematic inflammatory factors, intestinal integrity and inflammation were evaluated using hematoxylin and eosin staining, immunohistochemistry, immunofluorescence and Western blot analysis. Voglibose ameliorated glucose metabolism by enhancing basal- and glucose-dependent GLP-1 secretion. Several beneficial SCFAs, such as acetic acid and propionic acid, were increased by voglibose in the fecal sample. Additionally, voglibose notably decreased the proportion of pro-inflammatory macrophages and the expression of nuclear factor kappa B but increased the expression of tight junction proteins in the ileum, thus markedly improving intestinal inflammatory damage and reducing the systematic inflammatory factors. Ileal genomics and protein validation suggested that voglibose attenuated inositol-requiring protein 1α-X-box binding protein 1-mediated endoplasmic reticulum stress (ERS). Together, these results showed that voglibose enhanced the secretion of GLP-1, which contributed to the glycemic control in KKAy mice at least in part by regulating intestinal inflammation and the expression of ERS factors.

Topics: Animals; Diabetes Mellitus, Type 2; Glucagon-Like Peptide 1; Glucose; Ileum; Inositol; Mice

Topics: Animals; Antioxidants; Azoxymethane; Biomarkers; Biopsy; Cell Proliferation; Colonic Neoplasms; Cytokines; Diabetes Mellitus, Type 2; Disease Models, Animal; Glycoside Hydrolase Inhibitors; Humans; Inflammation Mediators; Inositol; Intestinal Mucosa; Mice; NF-kappa B; Obesity; Oxidative Stress; Precancerous Conditions

Postprandial hyperglycemia considered to be a major risk factor for cerebrovascular complications.. The current study was designed to elucidate the beneficial role of voglibose via in-silico in vitro to in-vivo studies in improving the postprandial glycaemic state by protection against strokeprone type 2 diabetes.. In-Silico molecular docking and virtual screening were carried out with the help of iGEMDOCK+ Pymol+docking software and Protein Drug Bank database (PDB). Based on the results of docking studies, in-vivo investigation was carried out for possible neuroprotective action. T2DM was induced by a single injection of streptozotocin (90mg/kg, i.v.) to neonates. Six weeks after induction, voglibose was administered at the dose of 10mg/kg p.o. for two weeks. After eight weeks, diabetic rats were subjected to middle cerebral artery occlusion, and after 72 hours of surgery, neurological deficits were determined. The blood was collected for the determination of serum glucose, CK-MB, LDH and lipid levels. Brains were excised for determination of brain infarct volume, brain hemisphere weight difference, Na+-K+ ATPase activity, ROS parameters, NO levels, and aldose reductase activity.. In-silico docking studies showed good docking binding score for stroke associated proteins, which possibly hypotheses neuroprotective action of voglibose in stroke. In the present in-vivo study, pre-treatment with voglibose showed a significant decrease (p<0.05) in serum glucose and lipid levels. Voglibose has shown significant (p<0.05) reduction in neurological score, brain infarct volume, the difference in brain hemisphere weight. On biochemical evaluation, treatment with voglibose produced significant (p<0.05) decrease in CK-MB, LDH, and NO levels in blood and reduction in Na+-K+ ATPase, oxidative stress, and aldose reductase activity in brain homogenate.. In-silico molecular docking and virtual screening studies and in-vivo studies in MCAo induced stroke, animal model outcomes support the strong anti-stroke signature for possible neuroprotective therapeutics.

Topics: Animals; Cerebrovascular Disorders; Computer Simulation; Diabetes Mellitus, Experimental; Diabetes Mellitus, Type 2; Disease Models, Animal; Drug Evaluation, Preclinical; Humans; Hyperglycemia; Infarction, Middle Cerebral Artery; Inositol; Lipids; Molecular Docking Simulation; Neuroprotective Agents; Nitric Oxide; Rats; Risk Factors; Sodium-Potassium-Exchanging ATPase; Software; Stroke; User-Computer Interface

Topics: Diabetes Mellitus, Type 2; Humans; Hypoglycemic Agents; Inositol; Metformin

Topics: Diabetes Mellitus, Type 2; Humans; Hypoglycemic Agents; Inositol; Metformin

Soft-drink diabetic ketosis, characterized by acute onset ketosis induced by excessive ingestion of sugar-containing drinks, is often seen in obese, young patients, even with undiagnosed type 2 diabetes. We herein report a 15-year-old obese patient with the apolipoprotein E4/2 phenotype, in whom eruptive xanthomas lead to a diagnosis of soft-drink diabetic ketosis. He developed multiple asymptomatic yellowish papules on the auricles, back, buttocks and the extensor surfaces of the elbows and knees. He initially visited a dermatology clinic and his blood triglyceride and HbA1c levels were found to be 6,490 mg/dL and 16.5%, respectively. He was referred to our hospital for treatment of hyperglycemia and hypertyriglyceridemia. On admission, he had ketonuria and increased blood levels of 3-hydroxybutylate and acetoacetate. He habitually drank 1-3 litters of sweet beverages daily to quench his thirst. Therefore, "soft-drink diabetic ketosis" was diagnosed. Severe hypertriglyceridemia was considered to have been a consequence of impaired insulin action and his apolipoprotein E4/2 phenotype. We treated the diabetic ketosis and hypertriglyceridemia with intensive insulin therapy and a fat-restricted diet. At discharge, he no longer required insulin therapy and his blood glucose levels were controlled with metformin and voglibose. Along with amelioration of the hyperglycemia, triglyceride levels decreased to 247 mg/dL without administration of anti-hyperlipidemia agents. The eruptive xanthoma lesions gradually diminished in size and number and eventually disappeared by 12 months. This case provides an instructive example of eruptive xanthomas serving as a sign of severe dysregulation, not only of lipid, but also glucose, metabolism.

Topics: 3-Hydroxybutyric Acid; Acetoacetates; Adolescent; Apolipoprotein E2; Apolipoprotein E4; Carbonated Beverages; Diabetes Mellitus, Type 2; Diabetic Ketoacidosis; Diet, Fat-Restricted; Glycated Hemoglobin; Humans; Hypertriglyceridemia; Hypoglycemic Agents; Inositol; Insulin; Ketosis; Male; Metformin; Obesity; Xanthomatosis

Insulin injection, especially with insulin analogs, occasionally induces the production of insulin antibodies with high binding capacity and low affinity, similar to the insulin autoantibodies characteristic of insulin autoimmune syndrome (IAS). Production of these "IAS-like" insulin antibodies causes marked glycemic fluctuations with postprandial hyperglycemia and fasting hypoglycemia.. A 66-year-old man with a 27-year history of diabetes was admitted because of marked glycemic fluctuations. Human insulin treatment had been initiated at age 56, followed by multiple daily injections of insulin analogs 5 years later. After the initial year of insulin analog treatment, the patient began to experience frequent morning hypoglycemic attacks and day-time hyperglycemia. Marked hyperinsulinemia (4500 μU/mL) and high titers of insulin antibodies (80.4%) with high binding capacity and low affinity indicated that IAS-like insulin antibodies were causing severe glucose fluctuations. Altering insulin formulations (insulin aspart → regular human insulin→ insulin lispro) proved to be ineffective. After several therapeutic trials, cessation of exogenous insulin and addition of mitiglinide to liraglutide with voglibose finally attenuated glycemic fluctuations with increased postprandial insulin secretion. Continuous glucose monitoring revealed improvement of morning hypoglycemia and postprandial hyperglycemia with smaller mean amplitude of glycemic excursion. Therefore, compared to exogenously injected insulin, endogenously secreted insulin directly and rapidly acts on hepatocytes and suppresses postprandial glucose output.. Proper enhancement of postprandial endogenous insulin aimed at suppressing postprandial glucose output without stimulating excessive glucose uptake in the periphery is potentially useful for treating diabetes with insulin antibody-induced glycemic instability.

Topics: Aged; Blood Glucose; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Drug Therapy, Combination; Glycated Hemoglobin; Humans; Hyperglycemia; Hypoglycemia; Hypoglycemic Agents; Inositol; Insulin; Insulin Antibodies; Insulin Secretion; Isoindoles; Liraglutide; Male; Postprandial Period; Treatment Outcome

Endothelial dysfunction contributes to poor cardiovascular prognosis in patients with type 2 diabetes mellitus (T2DM) and coronary artery disease (CAD). The effect of dipeptidyl peptidase-4 inhibitors on endothelial function remains controversial. We sought to compare the effects of linagliptin and voglibose on endothelial function, as assessed by reactive hyperemia-peripheral arterial tonometry (RH-PAT). Sixteen patients with newly diagnosed T2DM and CAD were randomized 1:1 to linagliptin (5 mg, once-daily) or voglibose (0.9 mg, thrice-daily). The RH-PAT and laboratory parameters, including 75 g oral glucose tolerance test, were measured at baseline and 3 months. Linagliptin increased serum levels of active glucagon-like peptide-1 and high-molecular-weight adiponectin. Age-, sex-, and baseline-adjusted changes in logarithmic RH-PAT index (LnRHI) after 3 months were significant between groups (linagliptin, 0.135 ± 0.097; voglibose, - 0.124 ± 0.091; P = 0.047). In the linagliptin group, change in LnRHI was positively correlated with change in high-density lipoprotein cholesterol and negatively correlated with changes in both urine albumin-to-creatinine ratio and high-sensitivity C-reactive protein. Furthermore, linagliptin treatment for 3 months reduced serum levels of both glucose and insulin at 2 h, relative to voglibose, in the age-, sex-, and baseline-adjusted model. Linagliptin improved endothelial function relative to voglibose, accompanied by amelioration of glycemic, renal, and cardiometabolic parameters, in patients with newly diagnosed T2DM and CAD.Trial registration Unique Trial Number, UMIN 000029169 ( https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000012442 ).

Topics: Aged; Coronary Artery Disease; Diabetes Mellitus, Type 2; Dose-Response Relationship, Drug; Endothelium, Vascular; Female; Humans; Hypoglycemic Agents; Inositol; Linagliptin; Male; Middle Aged; Pilot Projects; Prognosis; Prospective Studies; Vasodilation

The present study was conducted to assess the cardiovascular effects of dipeptidyl peptidase-4 inhibitors (DPP4i) on coronary flow reserve (CFR), left ventricular (LV) function and endothelial function of the peripheral artery by comparison with those of α-glucosidase inhibitors (αGI) in patients with type 2 diabetes mellitus (T2DM) and coronary artery disease (CAD).Methods and Results:We randomly assigned 30 patients with T2DM and CAD to receive either sitagliptin or voglibose, and 28 patients (age 69±9 years, 75% male, hemoglobin A1c [HbA1c] 6.62±0.48%) completed the study (14 in each group). CFR and LV function, assessed by cardiac magnetic resonance imaging, and endothelial function, assessed by reactive hyperemia peripheral arterial tonometry (RH-PAT), were measured at baseline and 24 weeks after treatment. Clinical and laboratory parameters, including HbA1c level, plasma active glucagon-like peptide-1 concentrations, and biomarkers of inflammation, were unchanged in both groups after 24 weeks of treatment. CFR were unchanged in both the αGI group (3.01±0.98 at baseline and 3.06±0.8 after treatment, P=NS) and the DPP4i group (4.29±2.04 at baseline and 3.63±1.31 after treatment, P=NS), with no interaction effect. LV functional parameters and the reactive hyperemia index also remained unchanged after the 24-week treatment.. DPP4i did not improve CFR, LV function or endothelial function of the peripheral artery in patients with relatively well-controlled T2DM and CAD.

Topics: Aged; Coronary Artery Disease; Coronary Circulation; Diabetes Complications; Diabetes Mellitus, Type 2; Dipeptidyl-Peptidase IV Inhibitors; Endothelium, Vascular; Female; Glycated Hemoglobin; Humans; Hyperemia; Inositol; Magnetic Resonance Imaging; Male; Middle Aged; Sitagliptin Phosphate; Ventricular Function, Left

1. Amidst the new strategies being developed for the management of type 2 diabetes mellitus (T2DM) with both established and newer therapies, alpha glucosidase inhibitors (AGIs) have found a place in several treatment protocols. 2. The objectives of the review were: (a) to compile and evaluate the various clinical pharmacokinetic drug interaction data for AGIs such as acarbose, miglitol and voglibose; (b) provide perspectives on the drug interaction data since it encompasses coadministered drugs in several key areas of comorbidity with T2DM. 3. Critical evaluation of the interaction data suggested that the absorption and bioavailability of many coadministered drugs were not meaningfully affected from a clinical perspective. Therefore, on the basis of the current appraisal, none of the AGIs showed an alarming and/or overwhelming trend of interaction potential with several coadministered drugs. Hence, dosage adjustment is not warranted in the use of AGIs in T2DM patients in situations of comorbidity. 4. The newly evolving fixed dose combination strategies with AGIs need to be carefully evaluated to ensure that the absorption and bioavailability of the added drug are not impaired due to concomitant food ingestion.

Topics: 1-Deoxynojirimycin; Acarbose; Diabetes Mellitus, Type 2; Drug Interactions; Humans; Hypoglycemic Agents; Inositol

Many patients with type 2 diabetes mellitus(T2DM) do not achieve satisfactory glycemic control by monotherapy alone, and often require multiple oral hypoglycemic agents (OHAs). Combining OHAs with complementary mechanisms of action is fundamental to the management of T2DM. Fixed-dose combination therapy(FDC) offers a method of simplifying complex regimens. Efficacy and tolerability appear to be similar between FDC and treatment with individual agents. In addition, FDC can enhance adherence and improved adherence may result in improved glycemic control. Four FDC agents are available in Japan: pioglitazone-glimepiride, pioglitazone-metformin, pioglitazone-alogliptin, and voglibose-mitiglinide. In this review, the advantages and disadvantages of these four combinations are identified and discussed.

Topics: Diabetes Mellitus, Type 2; Drug Therapy, Combination; Humans; Hypoglycemic Agents; Inositol; Isoindoles; Metformin; Pioglitazone; Piperidines; Sulfonylurea Compounds; Thiazolidinediones; Uracil

Meal tolerance tests (MTTs) are usually conducted at breakfast after overnight fasting in type 2 diabetes mellitus (T2DM) patients, but differences in postprandial glycemic responses between meals have been reported.. We conducted MTTs at breakfast, lunch, and dinner to examine the effects of a fixed combination of 10 mg mitiglinide/0.2 mg voglibose (the combination) on glycemic/metabolic responses to meals during the day in T2DM patients. MTTs with unified meals were conducted in 11 T2DM patients before and after 4 weeks of treatment with the combination administered thrice daily before meals. Glycemic/metabolic profiles measured before and at 30, 60, and 120 min after each meal were compared between each meal and between the baseline and treatment periods.. The combination significantly reduced postprandial hyperglycemia after each meal. Postprandial AUC0 - 120 min for insulin significantly decreased after lunch and dinner compared with after breakfast, while insulin levels significantly increased at only 30 min after breakfast and dinner. The combination also significantly increased postprandial C-peptide and active glucagon-like peptide-1 levels, and reduced free fatty acid and triglyceride levels, but did not significantly affect glucagon levels compared with baseline, confirming that treatment with the combination improves postprandial responses in Japanese T2DM patients.

Topics: Aged; Blood Glucose; Breakfast; C-Reactive Protein; Diabetes Mellitus, Type 2; Drug Combinations; Fatty Acids, Nonesterified; Female; Glucagon; Glucagon-Like Peptide 1; Humans; Hyperglycemia; Hypoglycemic Agents; Inositol; Insulin; Isoindoles; Lunch; Male; Meals; Middle Aged; Postprandial Period; Triglycerides

The effects of the dipeptidyl peptidase-4 (DPP-4) inhibitor, linagliptin, alone and in combination with voglibose or exendin-4, on glycaemic control and body weight were assessed in an animal model of type 2 diabetes. Voglibose is an α-glucosidase inhibitor but also increases glucagon-like peptide 1 (GLP-1). Exendin-4 is a GLP-1 receptor agonist. Male Zucker Diabetic Fatty (ZDF) rats were dosed for 3 days, fasted overnight and a sucrose/glucose tolerance test was performed. Linagliptin (1mg/kg po) improved glucose tolerance by increasing plasma GLP-1 (active) and insulin secretion, whilst having no effect on body weight. Voglibose (1 and 10mg/kg po) reduced body weight, improved glycaemic control, reduced plasma insulin and increased total but not active GLP-1. The combination of linagliptin and voglibose significantly reduced body weight, improved glycaemic control and reduced plasma insulin compared to linagliptin alone. Furthermore, linagliptin plus voglibose produced a marked increase in GLP-1 (active) at 5min post-sucrose, compared to linagliptin, possibly because linagliptin prevented the degradation of GLP-1 secreted in response to voglibose. Exendin-4 (10μg/kg sc) significantly reduced body weight, improved glucose tolerance but reduced GLP-1 (active). The combination of linagliptin and exendin-4 significantly reduced body weight and improved glycaemic control but had no effect on plasma GLP-1. Overall it did not markedly improve glycaemic control compared to the individual drugs. The improved glucose control, reduced body weight and markedly increased plasma GLP-1 levels in animals given linagliptin with voglibose, suggests that this combination may be particularly beneficial in the treatment of type 2 diabetes.

Topics: Animals; Blood Glucose; Diabetes Mellitus, Type 2; Drug Therapy, Combination; Exenatide; Hypoglycemic Agents; Inositol; Linagliptin; Male; Peptides; Purines; Quinazolines; Rats; Rats, Zucker; Treatment Outcome; Venoms

Type 2 diabetes mellitus (DM) has a deleterious effect on dental implant integration into alveolar bone, thought to arise from impaired osteoblast function and consequent reduced bone turnover. However, whether controlling blood glucose with antidiabetic drugs is sufficient to improve implant integration is unclear. This study was designed to evaluate implant integration using diabetic rats with/without an antidiabetic drug.. Titanium screws were surgically implanted in each tibia of 20 Goto-Kakizaki (GK) rats and 5 nondiabetic control rats. After 3 or 9 weeks, osseointegration was determined by testing the removal torque required to displace the screw and by histological analysis of various parameters of bone formation.. Removal torque was significantly higher in the nondiabetic control group than in GK rats, irrespective of whether the GK rats had received voglibose. Histology revealed that single-labeled surface area was still high in the GK rats at 9 weeks but had peaked and diminished in control rats. Bone-implant contact area was reduced in GK rats.. Despite controlling blood glucose, voglibose was unable to reverse the bone metabolic effects of DM.

Topics: Alveolar Process; Animals; Biomechanical Phenomena; Dental Implants; Dental Stress Analysis; Diabetes Mellitus, Type 2; Disease Models, Animal; Hypoglycemic Agents; Inositol; Male; Mice, Inbred Strains; Osteogenesis; Rats; Rats, Wistar

This study compared glycemic variability in patients with type 2 diabetes given sitagliptin or voglibose.. Seventeen type 2 diabetes patients were given sitagliptin 50 mg/day or voglibose 0.9 mg/day for 2 months and were hospitalized for a 4-day evaluation by continuous glucose monitoring (CGM). On discharge, they were crossed over to the other regimen for 2 months of treatment/4 days of evaluation. The CGM data were used to compare each parameter for glycemic variability.. The average glucose levels with sitagliptin and voglibose were significantly different at 138.6 and 152.6 mg/dL for 24 h (P=0.014) and 147.2 and 160.9 mg/dL for during daytime (P=0.050), respectively. The patients' glucose levels with sitagliptin and voglibose were significantly different at 125.3 and 139.7 mg/dL before breakfast (P=0.015) and 112.7 and 131.4 mg/dL before lunch (P=0.049), respectively. The time from before meal to postprandial peak glucose levels was significantly longer after dinner with voglibose than with sitagliptin (91.5 and 122.3 min, respectively; P=0.012). All of the slopes of glucose elevation were significantly lower with voglibose after each meal, with that after breakfast, lunch, and dinner being 1.16 and 0.86 mg/dL/min (P=0.031), 0.70 and 0.45 mg/dL/min (P=0.048), and 1.06 and 0.73 mg/dL/min (P=0.028), respectively.. This CGM-based pilot study revealed that sitagliptin significantly lowered 24-h and daytime mean glucose levels and glucose levels before breakfast and lunch compared with voglibose, whereas the time from before dinner to peak postprandial glucose levels was significantly longer, and the slope of postprandial elevation of glucose level was significantly lower after each meal, with voglibose compared with sitagliptin.

Topics: Aged; Asian People; Blood Glucose; Body Mass Index; Diabetes Mellitus, Type 2; Drug Combinations; Female; Humans; Hyperglycemia; Hypoglycemic Agents; Inositol; Japan; Male; Middle Aged; Monitoring, Physiologic; Pilot Projects; Postprandial Period; Pyrazines; Sitagliptin Phosphate; Triazoles

The asymmetric synthesis of 1-C-alkyl-l-arabinoiminofuranoses 1 was achieved by asymmetric allylic alkylation (AAA), ring closing metathesis (RCM), and Negishi cross coupling as key reactions. Some of the prepared compounds showed potent inhibitory activities towards intestinal maltase, with IC(50) values comparable to those of commercial drugs such as acarbose, voglibose, and miglitol, which are used in the treatment of type 2 diabetes. Among them, the inhibitory activity (IC(50)=0.032μM) towards intestinal sucrase of 1c was quite strong compared to the above commercial drugs.

Topics: alpha-Glucosidases; Animals; Diabetes Mellitus, Type 2; Enzyme Inhibitors; Glycoside Hydrolase Inhibitors; Humans; Hypoglycemic Agents; Imino Furanoses; Rats

Topics: Diabetes Mellitus, Type 2; Glucose Intolerance; Humans; Hypoglycemic Agents; Inositol; Life Style; Patient Education as Topic; Risk Reduction Behavior

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.. 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.. 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.. 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.

Topics: Acarbose; Aged; Blood Glucose; Diabetes Mellitus, Type 2; Enzyme Inhibitors; Female; Glycoside Hydrolase Inhibitors; Humans; Hypoglycemic Agents; Inositol; Male; Middle Aged; Triglycerides

Topics: Diabetes Mellitus, Type 2; Disease Progression; Humans; Hypoglycemic Agents; Inositol

Topics: Blood Glucose; Diabetes Mellitus, Type 2; Disease Progression; Glycated Hemoglobin; Humans; Hypoglycemic Agents; Inositol

Topics: Administration, Oral; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Disease Progression; Edema; Humans; Hypoglycemic Agents; Inositol; Insulin, Isophane; Male; Middle Aged; Pericardial Effusion; Pleural Effusion; Sulfonylurea Compounds

E3024 (3-but-2-ynyl-5-methyl-2-piperazin-1-yl-3,5-dihydro-4H-imidazo[4,5-d]pyridazin-4-one tosylate) is a dipeptidyl peptidase IV (DPP-IV) inhibitor. Since the target of both DPP-IV inhibitors and alpha-glucosidase inhibitors is the lowering of postprandial hyperglycemia, we compared antihyperglycemic effects for E3024 and alpha-glucosidase inhibitors in various oral carbohydrate and meal tolerance tests using normal mice. In addition, we investigated the combination effects of E3024 and voglibose on blood glucose levels in a meal tolerance test using mice fed a high-fat diet. ER-235516-15 (the trifluoroacetate salt form of E3024, 1 mg/kg) lowered glucose excursions consistently, regardless of the kind of carbohydrate loaded. However, the efficacy of acarbose (10 mg/kg) and of voglibose (0.1 mg/kg) varied with the type of carbohydrate administered. The combination of E3024 (3 mg/kg) and voglibose (0.3 mg/kg) improved glucose tolerance additively, with the highest plasma active glucagon-like peptide-1 levels. This study shows that compared to alpha-glucosidase inhibitors, DPP-IV inhibitors may have more consistent efficacy to reduce postprandial hyperglycemia, independent of the types of carbohydrate contained in a meal, and that the combination of a DPP-IV inhibitor and an alpha-glucosidase inhibitor is expected to be a promising option for lowering postprandial hyperglycemia.

Topics: Acarbose; Administration, Oral; Animals; Area Under Curve; Blood Glucose; Carbohydrate Metabolism; Diabetes Mellitus, Type 2; Dietary Sucrose; Dipeptidyl-Peptidase IV Inhibitors; Drug Therapy, Combination; Enzyme Inhibitors; Food, Formulated; Glucagon-Like Peptide 1; Glucose Tolerance Test; Glycoside Hydrolase Inhibitors; Hyperglycemia; Hypoglycemic Agents; Imidazoles; Injections, Intravenous; Inositol; Insulin; Male; Mice; Mice, Inbred C57BL; Postprandial Period; Pyridazines; Tosyl Compounds

Topics: Aged; Diabetes Mellitus, Type 2; Glycoside Hydrolase Inhibitors; Humans; Hypoglycemic Agents; Inositol; Intestinal Pseudo-Obstruction; Male

To assess the possible difference in effectiveness of 2 alpha-glucosidase inhibitors, voglibose and acarbose, the relationship between postprandial hyperglycemia and subjective abdominal symptoms was investigated. A total of 21 inpatients with type 2 diabetes were recruited to a single-center, 2-period, crossover trial. The subjects were given acarbose (150 mg/d) or voglibose (0.9 mg/d) under an isocaloric diet, and the postprandial (2 hours) increment in blood glucose level, M value which is a marker for fluctuation of blood glucose levels, and subjective abdominal symptom score were monitored. There was no significant difference between the 2 agents in postprandial increment in blood glucose level, M value, and subjective symptom score. When patients were divided according to subjective symptoms, however, the sum postprandial glucose increments were significantly different according to the agent (P = .03), with favorable efficacy in patients in whom the alpha-glucosidase inhibitor caused abdominal symptoms, demonstrating a significant interaction (P = .04) between treatment and symptomatic grouping. The results demonstrated that 50 mg acarbose and 0.3 mg voglibose had similar overall effects on postprandial hyperglycemia as well as subjective symptoms, but marked interindividual variation existed. Subjective symptoms may be a predictor of the divergent clinical response to each agent.

Topics: Acarbose; Aged; Blood Glucose; Cross-Over Studies; Diabetes Mellitus, Type 2; Enzyme Inhibitors; Female; Flatulence; Food; Gastrointestinal Tract; Glycoside Hydrolase Inhibitors; Humans; Hyperglycemia; Inositol; Male; Middle Aged

The age-related changes in acute insulin response after glucose loading and the influence of suppression of body weight gain were investigated by using blood samples from portal and peripheral veins. We placed indwelling catheters in the portal vein of 12- and 24- wk-old Otsuka Long-Evans Tokushima fatty (OLETF) rats (n = 8, 12), and age-matched control Long-Evans Tokushima Otsuka (LETO) rats (n = 8, 6). To suppress the body weight gain, 6 out of 12 OLETF rats were fed chow containing 50 ppm voglibose (VOG) from 8 until 24 wk of age. After fasting for 17 h, rats underwent 1 g/kg oral glucose tolerance test (OGTT). Peripheral glucose levels after glucose loading were significantly higher in 12- and 24-wk-old OLETF rats than in the age-matched LETO rats. Values for delta insulin 15 min/delta glucose 15 min (delta I15 min/delta G15 min) in portal blood were 0.029 +/- 0.011 and 0.009 +/- 0.009 (12 wk of age) and 0.03 +/- 0.03 and -0.01 +/- 0.01 (24 wk of age) in the LETO rats and OLETF rats. At the age of 24 wk, the body weights in VOG-treated OLETF rats were significantly lower than those in the OLETF rats. And there was significantly greater acute insulin response to glucose in VOG-treated OLETF rats than in the OLETF rats. Acute insulin response to glucose decreased with advancing age and the suppression of body weight gain preserved the response in spontaneously type 2 diabetic rats with visceral fat obesity.

Topics: Animals; Blood Glucose; Diabetes Mellitus, Type 2; Fatty Acids, Nonesterified; Glucose; Glucose Tolerance Test; Hypoglycemic Agents; Immunohistochemistry; Inositol; Insulin; Islets of Langerhans; Obesity; Portal Vein; Prediabetic State; Rats; Rats, Inbred OLETF; Weight Gain

Short-term hypoglycemic effects of single dose voglibose and nateglinide were compared after sucrose loading in spontaneously diabetic Otsuka Long-Evans Tokushima fatty (OLETF) rats.. After a 17-h fasting period, the animals received 0.06 mg/kg of voglibose (VOG group, n = 6), 50 mg/kg of nateglinide (NAT group, n = 6), or 0.5% methyl cellulose (control group, n = 6), immediately followed by 2.5 g/kg of sucrose.. Compared to control group values, glucose levels after sucrose loading were significantly decreased in the portal blood in the VOG group and in the peripheral blood in the NAT and VOG groups. The portal glucose AUC0-120 min was significantly lower in the VOG group than in the control and NAT groups, whereas the peripheral glucose AUC0-120 min was significantly lower in the VOG and NAT groups than in the control group. Portal insulin levels in the VOG group were significantly decreased compared to the control group. However, portal insulin levels in the NAT group were acutely increased, peaking 15 min after sucrose loading. Portal FFA levels were decreased in the NAT group 15, 30, and 60 min after sucrose loading; no FFA reductions were seen in the VOG group.. Although both drugs produced similar hypoglycemic effects after sucrose loading in the peripheral blood, these drugs generated vastly different results in portal blood. Reduced FFA in the portal blood, observed after single administration of nateglinide, may have a favorable impact not only on glucose metabolism but also on lipid metabolism.

Topics: Animals; Area Under Curve; Blood Glucose; Cyclohexanes; Diabetes Mellitus, Type 2; Disease Models, Animal; Enzyme Inhibitors; Fatty Acids, Nonesterified; Hypoglycemic Agents; Inositol; Insulin; Insulin Secretion; Male; Nateglinide; Phenylalanine; Portal Vein; Postprandial Period; Rats; Rats, Inbred OLETF; Secretory Rate; Sucrose

The effect of long-term (6 months) administration of voglibose in a dietary mixture (10 ppm) on intestinal disaccharidase activity was examined in non obese type 2 diabetes model Goto-Kakizaki (GK) rats. The postprandial blood glucose level in voglibose-treated GK rats was significantly lower than in untreated GK rats (190+/-19 vs. 250+/-25 mg/dl, P<0.01; 1 h, 212+/-23 vs. 256+/-20, P<0.05; 2 h), and the activities of maltase, sucrase, and isomaltase remained significantly lower throughout the 6 months of voglibose treatment. The expressions of protein and mRNA of sucrase-isomaltase (SI) complex were significantly higher in voglibose-treated GK rats. Voglibose administration then was stopped after 6 months of treatment. The mRNA level and protein level of the SI complex became normalized during the interruption of drug administration, and disaccharidase activities increased almost to the level of the untreated group 1 month after treatment was stopped. After 1 day of re-administration of the drug, however, disaccharidase activities again became significantly inhibited. These results indicate that voglibose may improve glucose tolerance since it inhibits activities of disaccharidases in spite of increasing the expression of them on intestine, furthermore voglibose may be reversible and reproducible through interruption and re-administration.

Topics: Alkaline Phosphatase; Animals; Blood Glucose; Blotting, Northern; Blotting, Western; Body Weight; Diabetes Mellitus, Type 2; Disaccharidases; Disease Models, Animal; Eating; Enzyme Inhibitors; Inositol; Insulin; Intestinal Mucosa; Male; Rats; Rats, Wistar; RNA, Messenger

The Goto-Kakizaki (GK) rat, an animal model of type 2 diabetes, exhibits mild hyperglycemia with a reduction of beta-cell mass. The mechanism for islet structural changes in this model and whether the changes are affected by metabolic control are not known. In the present study, we examined the process of islet changes in male GK rats aged 6, 8, 12, 24, and 36 weeks. Treatment effects with an alpha-glucosidase inhibitor (Voglibose; Takeda, Osaka, Japan) for 24 weeks (12 to 36 weeks of age) were also evaluated. The beta-cell mass increased until 8 weeks of age in both GK and control rats, but the increase was significantly (P < .01) smaller in GK rats versus at 8 weeks of age. Thereafter, the beta-cell mass decreased in GK rats, whereas it remained constant in controls. Voglibose treatment significantly (P < .01) inhibited the reduction of beta-cell mass in GK rats. Proliferative activity of beta cells as measured by bromodeoxyuridine (BrdU) uptake was significantly (P < .05) lower in GK rats versus control rats at 6 and 8 weeks, but the difference disappeared after 12 weeks of age, regardless of Voglibose treatment. The present study thus demonstrates a progressive loss of beta cells in GK rats that was mitigated by Voglibose treatment. We consider that the beta-cell loss in GK rats was due to an early impairment in proliferative activity and reduced survival. Voglibose did not appear to stimulate beta-cell proliferation, but exerted its effect via a reduction of hyperglycemia.

Topics: Aging; Animals; Body Weight; Diabetes Mellitus, Type 2; Enzyme Inhibitors; Glycoside Hydrolase Inhibitors; Inositol; Islets of Langerhans; Male; Rats; Rats, Mutant Strains; Rats, Wistar

Topics: Acarbose; Aged; Aged, 80 and over; Cardiotonic Agents; Diabetes Mellitus, Type 2; Digoxin; Drug Interactions; Enzyme Inhibitors; Glycoside Hydrolase Inhibitors; Heart Failure; Humans; Hypoglycemic Agents; Inositol; Male

Diabetes mellitus is a rare complication of glycogen storage disease type III (GSD III).. We describe a 47-year-old man with GSD III who developed diabetes mellitus. He was diagnosed as having GSD III at the age of 18 years, and his glucose tolerance was normal at that time. Liver dysfunction and muscle atrophy gradually progressed, and the patient developed diabetes mellitus at the age of 45. When the post-prandial hyperglycaemia worsened, we instituted treatment with an alpha-glucosidase inhibitor, voglibose, and this improved glycaemic control without any adverse effects.. We recommend serial evaluation for complications of GSD III, and propose that an alpha-glucosidase inhibitor may be a favourable drug in treating diabetes mellitus secondary to GSD III.

Topics: Age of Onset; Blood Glucose; C-Peptide; Diabetes Mellitus, Type 2; Disease Progression; Enzyme Inhibitors; Glycogen Storage Disease Type III; Glycoside Hydrolase Inhibitors; Humans; Inositol; Insulin; Male; Middle Aged

Reactive oxygen species are involved in a diversity of biological phenomena such as inflammation, carcinogenesis, aging, and atherosclerosis. We and other investigators have shown that the level of 8-hydroxy-2'-deoxyguanosine (8-OHdG), a marker for oxidative stress, is increased in either the urine or the mononuclear cells of the blood of type 2 diabetic patients. However, the association between type 2 diabetes and oxidative stress in the pancreatic beta-cells has not been previously described. We measured the levels of 8-OHdG and 4-hydroxy-2-nonenal (HNE)-modified proteins in the pancreatic beta-cells of GK rats, a model of nonobese type 2 diabetes. Quantitative immunohistochemical analyses with specific antibodies revealed higher levels of 8-OHdG and HNE-modified proteins in the pancreatic beta-cells of GK rats than in the control Wistar rats, with the levels increasing proportionally with age and fibrosis of the pancreatic islets. We further investigated whether the levels of 8-OHdG and HNE-modified proteins would be modified in the pancreatic beta-cells of GK rats fed with 30% sucrose solution or 50 ppm of voglibose (alpha-glucosidase inhibitor). In the GK rats, the levels of 8-OHdG and HNE-modified proteins, as well as islet fibrosis, were increased by sucrose treatment but reduced by voglibose treatment. These results indicate that the pancreatic beta-cells of GK rats are oxidatively stressed, and that chronic hyperglycemia might be responsible for the oxidative stress observed in the pancreatic beta-cells.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Aldehydes; Animals; Blood Glucose; Deoxyguanosine; Diabetes Mellitus, Type 2; Enzyme Inhibitors; Hyperglycemia; Immunohistochemistry; Inositol; Insulin; Islets of Langerhans; Oxidative Stress; Proteins; Rats; Rats, Inbred Strains; Solutions; Sucrose

Topics: Blood Glucose; Diabetes Mellitus, Type 2; Enzyme Inhibitors; Glycoside Hydrolase Inhibitors; Humans; Inositol; Insulin; Insulin Resistance; Insulin Secretion; Treatment Outcome

We observed 3 diabetic patients with intolerable dizziness followed by nausea and vomiting immediately after an initial administration of the alpha-glucosidase inhibitor, voglibose. These symptoms did not recur after discontinuation of the drug. Adverse effects as observed in these cases have not been reported previously. Since the 3 patients were relatively old (average age, 72 years old) and had various degrees of micro- and macroangiopathies, these side effects may have been associated with increased micro- and macrocirculatory disturbances in their central nervous systems through alpha-glucosidase inhibition of this agent.

Topics: Aged; Aged, 80 and over; Cerebral Infarction; Cerebrovascular Circulation; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Dizziness; Enzyme Inhibitors; Female; Glycoside Hydrolase Inhibitors; Humans; Hypoglycemic Agents; Inositol; Male; Middle Aged; Nausea; Vomiting

Effects of voglibose (an alpha-glucosidase inhibitor) and pioglitazone (an insulin sensitizer) on glycemic control and on the function of pancreatic islets were evaluated using Goto-Kakizaki (GK) rats with non-insulin-dependent diabetes mellitus (NIDDM). Five week administration (8-13 weeks of age in GK rats) of voglibose alone (added to the chow at a concentration of 10 ppm), pioglitazone alone (10 mg/kg daily p.o.), or both of the agents together significantly improved fasting plasma glucose levels and those at 120 min in oral glucose tolerance tests. Insulin secretory capacity in response to glucose of the isolated islets, assessed by batch incubation, was significantly improved in the voglibose and in the voglibose plus pioglitazone groups. Eight-week administration (5-13 weeks of age) of voglibose and voglibose plus pioglitazone successfully lowered the fasting levels of plasma glucose and triglyceride. The glucose-responsiveness in insulin release from the islets was also significantly recovered by the therapy. The treatment increased the insulin content of the islets to almost twice that in untreated controls. Thus, treatment by these drugs can not only effectively ameliorate the metabolic derangement of NIDDM in GK rats, but it can also restore the deteriorated islet function, possibly through protection from glucose toxicity.

Topics: Animals; Blood Glucose; Cholesterol; Diabetes Mellitus, Type 2; Enzyme Inhibitors; Fasting; Glucose Tolerance Test; Glycoside Hydrolase Inhibitors; Hypoglycemic Agents; Inositol; Insulin; Insulin Secretion; Islets of Langerhans; Male; Pioglitazone; Rats; Rats, Mutant Strains; Rats, Wistar; Thiazoles; Thiazolidinediones; Triglycerides

Topics: Biomarkers; Deoxyglucose; Diabetes Mellitus, Type 2; Enzyme Inhibitors; Female; Glycoside Hydrolase Inhibitors; Humans; Inositol; Isomerism; Male; Middle Aged

Topics: Adult; Aged; Blood Glucose; Diabetes Mellitus, Type 2; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Therapy, Combination; Enzyme Inhibitors; Female; Glycated Hemoglobin; Glycoside Hydrolase Inhibitors; Humans; Hypoglycemic Agents; Inositol; Male; Middle Aged

Alpha-glucosidase inhibitor can suppress postprandial hyperglycemia by delaying the absorption of carbohydrates in the intestine, and may be useful in obese patients with non-insulin-dependent diabetes mellitus (NIDDM) and preserved insulin secretion. We encountered an obese elderly patient with NIDDM in whom gait disturbance had developed after cerebral hemorrhage and who suffered from ileus after treatment with voglibose. The patient had received voglibose which is reported to cause fewer abdominal symptoms than acarbose, for 15 days. The patient, a 63-year-old woman, was given a diagnosis of NIDDM in February 1995, and was treated with a sulfonylurea agent. However, her glycemic control remained poor and she was admitted to our hospital in April 1995. Her body mass index was 30.5 kg/m2 and laboratory investigation revealed a fasting plasma glucose level of 211 mg/dl, a postprandial (2 h) plasma glucose level of 288 mg/dl, HbAlc of 9.9%, a fasting insulin level of 9 microU/ml, urinary C-peptide excretion of 95.7 micrograms/ day, and an coefficient of variation of R-R value of 2.1%. Fifteen days after glibenclamide was replaced by to voglibose, abdominal pain, nausea, constipation, and ausculatory sounds of gurgling developed, and niveau were noted on an abdominal roentgenogram which indicated that simple ileus had developed. Voglibose was discontinued and the patient was treated with an enema and hot air. She recovered from simple ileus on the next day. This patient had had two abdominal surgeries and a cerebral hemorrhage, and her daily physical activities were limited, which might have contributed to ileus. In elderly patients with NIDDM, a history of abdominal surgery and the amount of daily exercise must be considered when deciding whether or not to give alpha-glucosidase inhibitors.

Topics: Cerebral Hemorrhage; Cyclohexanols; Diabetes Mellitus; Diabetes Mellitus, Type 2; Enzyme Inhibitors; Female; Gait; Glycoside Hydrolase Inhibitors; Humans; Intestinal Obstruction; Middle Aged; Obesity