ao-128 and Glucose-Intolerance

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

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

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

We evaluated the effects of an alpha-glucosidase inhibitor, voglibose, on cardiovascular events in patients with a previous myocardial infarction (MI) and impaired glucose tolerance (IGT).. This prospective, randomized, open, blinded-endpoint study was conducted in 112 hospitals and clinics in Japan in 3000 subjects with both previous MI and IGT receiving voglibose (0.6 mg/day, n = 424) or no drugs (n = 435) for 2 years. The Data and Safety Monitoring Board (DSMB) recommended discontinuation of the study in June 2012 after an interim analysis when the outcomes of 859 subjects were obtained. The primary endpoint was cardiovascular events including cardiovascular death, nonfatal MI, nonfatal unstable angina, nonfatal stroke, and percutaneous coronary intervention/coronary artery bypass graft. Secondary endpoints included individual components of the primary endpoint in addition to all-cause mortality and hospitalization due to heart failure.. The age, ratio of males, and HbA. Although voglibose effectively treated IGT, no additional benefits for cardiovascular events in patients with previous MI and IGT were observed. Voglibose may not be a contributing therapy to the secondary prevention in patients with MI and IGT.. Clinicaltrials.gov number: NCT00212017.

Topics: Aged; Cardiovascular Diseases; Female; Glucose Intolerance; Glycoside Hydrolase Inhibitors; Humans; Hypoglycemic Agents; Inositol; Japan; Kaplan-Meier Estimate; Male; Middle Aged; Myocardial Infarction; Prospective Studies; Secondary Prevention; Treatment Outcome

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

Topics: Adult; Area Under Curve; Blood Glucose; Cross-Over Studies; Drug Administration Schedule; Eating; Glucose Intolerance; Humans; Hypoglycemic Agents; Inositol; Insulin; Male; Postprandial Period

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

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; Glucose Intolerance; Humans; Hypoglycemic Agents; Inositol; Life Style; Patient Education as Topic; Risk Reduction Behavior

Since 1) dilated cardiomyopathy (DCM) causes chronic heart failure (CHF), and 2) augmentation of neurohumoral factors such as angiotensin II impairs glucose metabolism, we examined the rate of abnormal glucose metabolism in patients having both DCM and CHF and whether correction of the impairment of glucose metabolism would improve the pathophysiology of CHF in DCM patients. A 75-g oral glucose tolerance test (OGTT) was performed in 56 patients with DCM-induced CHF and 168 age- and sex-matched control subjects. Among the CHF patients, 26.8% and 50.0% suffered from diabetes mellitus (DM) and impaired glucose tolerance (IGT), respectively, showing that abnormal glucose tolerance was more prevalent in DCM patients than in the control subjects (7.7% and 14.3%, respectively). In the patients with DCM-induced CHF, a correlation was observed between the brain natriuretic peptide (BNP) levels and the difference between the plasma glucose levels at the time of fasting and at 2 h of OGTT. Since neither DM nor IGT are thought to cause DCM, the abnormalities of glucose metabolism may be attributed to the progression of CHF. Furthermore, we tested whether correction of the abnormal glucose tolerance using voglibose (an alpha-glucosidase inhibitor) would improve the severity of CHF in another group of 30 patients with DCM-induced CHF and IGT. The patients treated with voglibose for 24 weeks showed decreases in left ventricular dimension, NYHA functional classification values, and plasma BNP levels, and an improvement in cardiac function. In conclusion, abnormal glucose tolerance was more prevalent among patients with DCM-induced CHF than controls, and the correction of IGT improved the pathophysiology of CHF.

Topics: Cardiomyopathy, Dilated; Chronic Disease; Disease Progression; Echocardiography; Female; Glucose Intolerance; Glucose Tolerance Test; Heart Failure; Humans; Hypoglycemic Agents; Inositol; Male; Middle Aged; Natriuretic Peptide, Brain; Prevalence; Severity of Illness Index