ao-128 and miglitol

Despite considerable literature supporting the potential health benefits of reducing postprandial glucose (PPG), and insulin (PPI) exposures, the size of a clinically relevant reduction is currently unknown. We performed a systematic review and meta-analysis to quantify effects of alpha-glucosidase-inhibiting (AGI) drugs on acute PPG and PPI responses.. We searched EMBASE and MEDLINE until March 13, 2018 for controlled studies using AGI drugs together with a standardized carbohydrate load or mixed meal. The mean incremental PPG and PPI levels were calculated as outcomes. Meta-analyses, stratified by diabetes state, were performed by using random effects models.. The 66 included publications comprised 127 drug-control comparisons for PPG, and 106 for PPI, mostly testing acarbose or miglitol. The absolute effects on PPG were larger among individuals with diabetes (-1.5 mmol/l mean PPG [95% CI -1.9, -1.1] by acarbose, and -1.6 [-1.9, -1.4] by miglitol) as compared to individuals without diabetes (-0.4 [95% CI -0.5, -0.3] by acarbose, and -0.6 [-0.8, -0.4] by miglitol). Relative reductions in PPG by both drugs were similar for diabetic and non-diabetic individuals (43-54%). Acarbose and miglitol also significantly reduced mean PPI, with absolute and relative reductions being largest among individuals without diabetes.. The present meta-analyses provide quantitative estimates of reductions of PPG and PPI responses by AGI drugs in diabetes and non-diabetic individuals. These data can serve as benchmarks for clinically relevant reductions in PPG and PPI via drug or diet and lifestyle interventions.

Topics: 1-Deoxynojirimycin; Acarbose; Diabetes Mellitus; Glucose; Glycoside Hydrolase Inhibitors; Humans; Inositol; Insulin; Postprandial Period

The alpha (α)-amylase is a calcium metalloenzyme that aids digestion by breaking down polysaccharide molecules into smaller ones such as glucose and maltose. In addition, the enzyme causes postprandial hyperglycaemia and blood glucose levels to rise. α-Amylase is a well-known therapeutic target for the treatment and maintenance of postprandial blood glucose elevations. Various enzymatic inhibitors, such as acarbose, miglitol and voglibose, have been found to be effective in targeting this enzyme, prompting researchers to express an interest in developing potent alpha-amylase inhibitor molecules. The review mainly focused on designing different derivatives of drug molecules such as benzofuran hydrazone, indole hydrazone, spiroindolone, benzotriazoles, 1,3-diaryl-3-(arylamino) propan-1-one, oxadiazole and flavonoids along with their target-receptor interactions, IC

Topics: 1-Deoxynojirimycin; Acarbose; alpha-Amylases; Benzofurans; Blood Glucose; Diabetes Mellitus; Drug Discovery; Flavonoids; Glycoside Hydrolase Inhibitors; Humans; Hydrazones; Hypoglycemic Agents; Indoles; Inositol; Oxadiazoles; Structure-Activity Relationship

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 have been available for clinical use for about 20 years. They have shown reasonably good efficacy comparable to other oral blood glucose lowering drugs and in some parts of the world are the most commonly prescribed oral diabetes medication, especially in Asian countries. Unlike as has been observed with some other blood glucose lowering agents, however, no adverse signals of potential cardiovascular harm have emerged in relation to their use. On the contrary, significant beneficial cardiovascular outcome results have been observed in the post-hoc analyses of randomised placebo-controlled trials with the alpha-glucosidase inhibitor acarbose. Targeting mainly postprandial hyperglycaemia, alpha-glucosidase inhibitors favourably affect several cardiovascular risk factors, such as obesity, hypertension and high glycaemic variability with little to no risk for hypoglycaemia. Furthermore, acarbose favourably affects endothelial dysfunction and carotid intima media thickening in humans and, in animal models, improves cardiac interstitial fibrosis and hypertrophy of cardiomyocytes. The ultimate determination of the cardiovascular effects of alpha-glucosidase inhibitors in terms of clinical outcomes awaits the results of ongoing long-term, randomised, placebo-controlled trials.

Topics: 1-Deoxynojirimycin; Acarbose; Cardiovascular Diseases; Diabetes Complications; Glycoside Hydrolase Inhibitors; Humans; Hyperglycemia; Hypoglycemic Agents; Inositol

Topics: 1-Deoxynojirimycin; Acarbose; Digestive System Diseases; Drug Interactions; Enzyme Inhibitors; Glycoside Hydrolase Inhibitors; Humans; Hyperammonemia; Hypoglycemia; Hypoglycemic Agents; Imino Pyranoses; Inositol

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

It is widely accepted that the most challenging goal in the management of patients with diabetes mellitus is to achieve blood glucose levels as close to normal as possible. In general, normalising postprandial blood glucose levels is more difficult than normalising fasting hyperglycaemia. In addition, some epidemiological studies suggest that postprandial hyperglycaemia (PPHG) or hyperinsulinaemia are independent risk factors for the development of macrovascular complications of diabetes mellitus. Recently, several drugs with differing pharmacodynamic profiles have been developed which target PPHG. These include insulin lispro, amylin analogues, alpha-glucosidase inhibitors and meglitinide analogues. Insulin lispro has a more rapid onset of action and shorter duration of efficacy compared with regular human insulin. In clinical trials, the use of insulin lispro was associated with improved control of PPHG and a reduced incidence of hypoglycaemic episodes. Repaglinide, a meglitinide analogue, is a short-acting insulinotropic agent which. when given before meals, stimulates endogenous insulin secretions and lowers postprandial hyperglycaemic excursions. Both insulin lispro and repaglinide are associated with postprandial hyperinsulinaemia. In contrast, amylin analogues reduce PPHG by slowing gastric emptying and delivery of nutrients to the absorbing surface of the gut. Alpha-Glucosidase inhibitors such as acarbose, miglitol and voglibose also reduce PPHG primarily by interfering with the carbohydrate-digesting enzymes and delaying glucose absorption. With the availability of agents which preferentially reduce postprandial blood glucose excursions, it is now possible to achieve glycaemic goals in a larger proportion of individuals with diabetes mellitus.

Topics: 1-Deoxynojirimycin; Acarbose; Amyloid; Carbamates; Diabetes Mellitus; Enzyme Inhibitors; Glucosamine; Glyburide; Humans; Hyperglycemia; Hypoglycemic Agents; Imino Pyranoses; Inositol; Insulin; Insulin Lispro; Islet Amyloid Polypeptide; Piperidines; Postprandial Period; Trisaccharides

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

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

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

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

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

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

Carbohydrate hydrolyzing α-glucosidases are commonly found in microorganisms present in the human intestine microbiome. We have previously reported crystal structures of an α-glucosidase from the human gut bacterium Blaubia (Ruminococcus) obeum (Ro-αG1) and its substrate preference/specificity switch. This novel member of the GH31 family is a structural homolog of human intestinal maltase-glucoamylase (MGAM) and sucrase-isomaltase (SI) with a highly conserved active site that is predicted to be common in Ro-αG1 homologs among other species that colonize the human gut. In this report, we present structures of Ro-αG1 in complex with the antidiabetic α-glucosidase inhibitors voglibose, miglitol, and acarbose and supporting binding data. The in vitro binding of these antidiabetic drugs to Ro-αG1 suggests the potential for unintended in vivo crossreaction of the α-glucosidase inhibitors to bacterial α-glucosidases that are present in gut microorganism communities. Moreover, analysis of these drug-bound enzyme structures could benefit further antidiabetic drug development.

Topics: 1-Deoxynojirimycin; alpha-Glucosidases; Bacterial Proteins; Gastrointestinal Microbiome; Glycoside Hydrolase Inhibitors; Humans; Hypoglycemic Agents; Inositol; Models, Molecular; Protein Binding; Ruminococcus

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

Detailed imaging studies of gas cysts in the intestinal mucosa (pneumatosis cystoides intestinalis) have been reported in around 20 patients taking acarbose, miglitolor voglibose, i.e. intestinal alpha-glucosidase inhibitors used as hypoglycaemic agents. Almost all the patients had nonspecific abdominal symptoms such as abdominal pain, abdominal distension, rectal bleeding or loss of appetite. They underwent multiple diagnostic tests before a role of the drug was raised. The disorders resolved completely when the drugs were withdrawn. In practice, as acarbose and miglitol have no proven impact on morbidity or mortality, and as they have multiple adverse effects, including gas cysts, they should not be used to treat diabetic patients.

Topics: 1-Deoxynojirimycin; Acarbose; Aged; Aged, 80 and over; alpha-Glucosidases; Enzyme Inhibitors; Female; Gases; Glycoside Hydrolase Inhibitors; Humans; Hypoglycemic Agents; Inositol; Intestinal Mucosa; Male; Middle Aged; Pneumatosis Cystoides Intestinalis; Predictive Value of Tests; Risk Assessment; Risk Factors

An HPLC-UV method has been developed for the determination of valibose, miglitol, voglibose and acarbose, the four anti-diabetic drugs. The separation was accomplished successfully by using reversed phase chromatography (Prevail carbohydrate column, 250 mm x 4.6 mm, 5 microm) with a gradient acetonitrile-phosphate buffer solution (pH 8.0) at a wavelength of 210 nm. Furthermore, the method of a high-performance liquid chromatography coupled with ESI-MS in positive ionization mode has been established. These two methods were successfully applied to the assay and qualitative detection of four alpha-glucosidase inhibitors in the potential counterfeit anti-diabetic drugs.

Topics: 1-Deoxynojirimycin; Acarbose; alpha-Glucosidases; Chromatography, High Pressure Liquid; Chromatography, Reverse-Phase; Glycoside Hydrolase Inhibitors; Hypoglycemic Agents; Inositol; Spectrometry, Mass, Electrospray Ionization; Spectrophotometry, Ultraviolet

Topics: 1-Deoxynojirimycin; 3-Mercaptopropionic Acid; Acarbose; Animals; Carbohydrate Metabolism; Cyclohexanols; Cycloserine; Disaccharidases; Gluconeogenesis; Glucosamine; Humans; Hydrazines; Imino Pyranoses; Liver; Oleic Acids; Trisaccharides