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Type-II diabetes mellitus is a chronic disorder that results from fluctuations in the glucose level leading to hyperglycemia with severe adverse effects increasing worldwide. Alpha-Amylase is the key enzyme involved in the mechanism of glucose formation therefore Alpha-Amylase inhibitors have become a therapeutic target in the development of new leads as they have the potential to suppress glucose levels. Existing drugs targeting Alpha-Amylase highlight major drawbacks in terms of poor absorption rate that causes several gastrointestinal issues. So, this research is aimed to develop novel inhibitors interacting with Alpha-Amylase's active site using structural-based screening, binding pattern analysis, and molecular dynamic simulation. Hence, to search for a potential lead, we analyzed a total of 133 valiolamine derivatives and 535 desoxynojirimycin derivatives that exhibited drug-like properties screened through Lipinski filters. Virtual screening followed by binding interaction analysis we identified ten compounds that exhibited better binding energy scores compared to the standard drugs voglibose and miglitol, used in our study. The docking analysis, ADMET and metabolic site prediction estimated the best top two compounds with good drug profiles. Further, top compounds VG9 and VG15 were promoted to simulation study using the Biovia Discovery study to access the stability at a time interval of 100 ns. MD simulation results revealed that our compound VG9 possesses better conformational stability in the complex to the active site residues of Alpha-Amylase target protein than standard drug voglibose. Thus, our investigation revealed that compound VG9 also exhibits the best pharmacokinetic as well as binding affinity results and could act as a potential lead compound targeting Alpha-Amylase for Type II diabetes. [ABSTRACT FROM AUTHOR]

Aims: We aimed to identify patients who would benefit from basal insulin-supported oral therapy (BOT) with a glinide and an α-glucosidase inhibitor (a fixed-dose combination tablet of mitiglinide 10 mg and voglibose 0.2 mg) in Japanese type 2 diabetic patients. Methods: Patients who were hospitalized to improve hyperglycemia received basal–bolus insulin therapy. After the reduction of glucose toxicity, a 75 g oral glucose tolerance test and a glucagon test were performed. Thereafter, the basal–bolus insulin therapy was switched to BOT with mitiglinide, followed by further addition of voglibose. Interstitial glucose levels were continuously monitored throughout the study period. Diurnal glucose profile was recorded and analyzed. Patients were divided into two groups according to whether their percentage of time in range (TIR, 70–180 mg/dL) under BOT with mitiglinide/voglibose was higher than 70% or not, and the differences in clinical characteristics between the groups were analyzed. Results: Twenty patients were enrolled, and 19 of them completed the study. BOT with mitiglinide/voglibose achieved ≥ 70% of TIR in thirteen patients. The area under the curve of serum C-peptide levels during the oral glucose tolerance test was significantly higher in the patients with ≥ 70% of TIR. The daily insulin dosages and blood glucose profiles were comparable between the two groups. Conclusions: The efficacy of BOT with mitiglinide/voglibose depended on residual insulin secretory abilities. This therapy would be a useful therapeutic option for patients with type 2 diabetes. [ABSTRACT FROM AUTHOR]

Peyer’s patches (PPs) are specialized gut-associated lymphoid tissues that initiate follicular helper T (Tfh)-mediated immunoglobulin A (IgA) response to luminal antigens derived from commensal symbionts, pathobionts, and dietary sources. IgA-producing B cells migrate from PPs to the small intestinal lamina propria and secrete IgA across the epithelium, modulating the ecological balance of the commensal microbiota and neutralizing pathogenic microorganisms. α-glucosidase inhibitors (α-GIs) are antidiabetic drugs that inhibit carbohydrate digestion in the small intestinal epithelium, leading to alterations in the commensal microbiota composition and metabolic activity. The commensal microbiota and IgA responses exhibit bidirectional interactions that modulate intestinal homeostasis and immunity. However, the effect of α-GIs on the intestinal IgA response remains unclear. We investigated whether α-GIs affect IgA responses by administering voglibose and acarbose to mice via drinking water. We analyzed Tfh cells, germinal center (GC) B cells, and IgA-producing B cells in PPs by flow cytometry. We also assessed pathogen-specific IgA responses. We discovered that voglibose and acarbose induced Tfh cells, GCB cells, and IgA-producing B cells in the PPs of the proximal small intestine in mice. This effect was attributed to the modification of the microbiota rather than a shortage of monosaccharides. Furthermore, voglibose enhanced secretory IgA (S-IgA) production against attenuated Salmonella Typhimurium. Our findings reveal a novel mechanism by which α-GIs augment antigen-specific IgA responses by stimulating Tfh-GCB responses in PPs, and suggest a potential therapeutic application as an adjuvant for augmenting mucosal vaccines. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) is an age-dependent neurodegenerative disease hallmarked by Amyloid-β (Aβ) aggregation, cognitive impairment, and neuronal and synaptic loss. In this study, AD was induced in male Wistar rats (n = 6) by the administration of intracerebroventricular-streptozotocin (ICV-STZ-3 mg/kg/day), and Voglibose (Vog) was administered at various doses (10, 25, and 50 mg/kg), while Galantamine (3 mg/kg) acted as a reference standard drug. Behavioral alterations in both spatial and non-spatial memory functions were evaluated in the experimental rats. At the end of the study, all experimental rats were sacrificed, and their brain parts, the cortex and hippocampus, were subjected to biochemical, western blot, and histopathological analysis. In our study results, the statistically significant dose-dependent results from the behavioral tests show the Voglibose-treated groups significantly improved (p < 0.0001) spatial and non-spatial memory functions when compared with ICV-STZ-treated group. Meanwhile, when compared with ICV-STZ-treated rats, treatment with Voglibose (10, 25, and 50 mg/kg) showed the activities of both acetylcholinesterase (AChE) and malondialdehyde (MDA) were significantly attenuated (p < 0.0001), while the operation of antioxidant enzymes was considerably enhanced (p < 0.0001). The molecular estimation showed that it significantly attenuates (p < 0.0001) the TNF-α, IL-1β, and CRP activity, and the western blot results demonstrate the significantly attenuated Aβ aggregation. The histopathological results showed that the Voglibose treatment had an effective improvement in clear cytoplasm and healthy neuronal cells. In conclusion, our results suggest that Voglibose has potent neuroprotective effects against the ICV-STZ-induced AD model. Furthermore, these results support the possibility of Voglibose as a therapeutic approach to improving cognitive function, suggesting that controlling Aβ aggregation might be a novel target for the development of AD. [ABSTRACT FROM AUTHOR]

Abstract Background Although diabetes is one of the most common side effects of clozapine, a medication for the treatment of schizophrenia, to the best of our knowledge no study exists on clozapine‐induced glucose intolerance or hypoglycemia in patients with schizophrenia. Case Presentation We report a case of schizophrenia with repeated reactive hypoglycemia due to abnormal glucose tolerance during clozapine treatment. During clozapine administration in patients with schizophrenia, it is necessary to monitor physical and psychiatric symptoms due to reactive hypoglycemia and hyperglycemia. If abnormal glucose tolerance is a concern, it should be promptly detected using blood or oral glucose tolerance tests. Conclusion Early intervention for impaired glucose tolerance may prevent clozapine discontinuation due to diabetes or hyperglycemia.

Background: Chronic surgical anaesthesia and uncontrolled hyperglycemia are bidirectional risk factors for the development of psychiatric, cerebrovascular, and cardiovascular diseases. Objective: The current study was designed to elucidate the neuroprotective effects of anti-diabetic agents in pre and post-surgical anaesthesia exposure on diabetic ischemic rats. Methods: The diabetes type-2 was induced and rats having more than 250 gm/dl blood glucose levels were considered for study. Administration of anaesthetic agents (ketamine 100 mg/kg IP, xylazine 10 mg/kg IP) were done pre and post MCAo surgery for 7 days. The treatment with anti-diabetic agents (voglibose, saxagliptin, repaglinide, dapagliflozin) was carried out after 7 days of Post MCAo surgery for one week. After treatment, assessment of neurobehavioral function was carried out using Morris Water Maze. After that, brains were excised and bloods were collected from all groups subjected for assessment of neuromodulator levels, oxidative stress parameters, serum biochemical biomarkers. Results: The treatment with voglibose and saxagliptin not only improved neuromodulator levels statistically significant (p

Abstract Aims Sodium glucose co‐transporter 2 inhibitors have diuretic effects in both patients with glycosuria and with natriuresis. We sought to assess the effect of luseogliflozin on estimated plasma volume (ePV) in patients with type 2 diabetes and heart failure with preserved ejection fraction (HFpEF). Methods and results This study was a post‐hoc analysis of the MUSCAT‐HF trial (UMIN000018395), a multicentre, prospective, open‐label, randomized controlled trial that assessed the effect of 12 weeks of luseogliflozin (2.5 mg, once daily, n = 83) as compared with voglibose (0.2 mg, three times daily, n = 82) on the reduction in brain natriuretic peptide (BNP) in patients with type 2 diabetes and HFpEF. The analysis compared the change in ePV calculated by the Straus formula from baseline to Weeks 4, 12, and 24, using a mixed‐effects model for repeated measures. We also estimated the association between changes in ePV and changes in other clinical parameters, including BNP levels. Luseogliflozin significantly reduced ePV as compared to voglibose at Week 4 {adjusted mean group‐difference −6.43% [95% confidence interval (CI): −9.11 to −3.74]}, at Week 12 [−8.73% (95%CI: −11.40 to −6.05)], and at Week 24 [−11.02% (95%CI: −13.71 to −8.33)]. The effect of luseogliflozin on these parameters was mostly consistent across various patient clinical characteristics. The change in ePV at Week 12 was significantly associated with log‐transformed BNP (r = 0.197, P = 0.015) and left atrial volume index (r = 0.283, P = 0.019). Conclusions Luseogliflozin significantly reduced ePV in patients with type 2 diabetes and HFpEF, as compared with voglibose. The reduction of intravascular volume by luseogliflozin may provide clinical benefits to patients with type 2 diabetes and HFpEF.

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. [ABSTRACT FROM AUTHOR]

The aim. The aim of the work was to establish the feasibility of development, determine the optimal composition and technology, and confirm the pharmacological effectiveness of combined tablets for treating type II diabetes. Materials and methods. Analytical research of the pharmaceutical market of drugs used for the treatment of type II diabetes was carried out using content analysis of official sources of information. The subjects of the study were medicinal products used to treat type II diabetes. A set of physicochemical and technological research methods was used to determine the quality parameters of the tabletting mass and tablets based on them. Results. According to the results of previous studies, similarities in the approaches to the pharmacotherapy of type II diabetes in the countries of Southeast Asia, the Western Pacific region, and Ukraine were established, which became the basis for conducting a market study of drugs with a sugar-lowering effect, namely, based on voglibose, with the aim of further including such drugs in the range of Ukrainian manufacturers. Furthermore, according to the results of physicochemical and technological studies, the composition and rational technology of obtaining tablets were established. Also, pharmacological studies have established that tablets with voglibose and solid dispersion of quercetin significantly prevent the development of glucose metabolism disorders caused by a high-sugar diet. In terms of the expressiveness of the hypocholesterolemic effect of the tablets and their constituent components, they are reliably superior to the comparison drug - metformin. Conclusions. According to the research results, the feasibility and relevance of the development of combined tablets with voglibose and solid dispersion of quercetin have been established. Furthermore, based on the investigated physicochemical and technological indicators, combined tablets' composition and rational technology were developed, and their specific pharmacological activity was proven. [ABSTRACT FROM AUTHOR]

Alpha-glucosidase inhibitor (αGIs)-induced pneumatosis intestinalis (PI) has been narrated in case reports but never systematically investigated. This study aimed to investigate the concurrency of PI and αGIs. A literature search was performed in PubMed, Google Scholar, WorldCat, and the Directory of Open-Access Journals (DOAJ) by using the keywords "pneumatosis intestinalis", "alpha-glucosidase inhibitors", and "diabetes". In total, 29 cases of αGIs-induced PI in 28 articles were included. There were 11 men, 17 women, and one undefined sex, with a median age of 67. The most used αGI was voglibose (44.8%), followed by acarbose (41.4%) and miglitol (6.8%). Nine (31%) patients reported concomitant use of prednisone/prednisolone with or without immunosuppressants. The main symptoms were abdominal pain (54.5%) and distention (50%). The ascending colon (55.2%) and the ileum (34.5%) were the most affected. Nineteen (65.5%) patients had comorbidities. Patients with comorbidities had higher rates of air in body cavities, the portal vein, extraintestinal tissues, and the wall of the small intestine. Only one patient was found to have non-occlusive mesenteric ischemia. Twenty-five patients were treated with conservative therapy alone, and two patients received surgical intervention. All patients recovered. In conclusion, comorbidities, glucocorticoids, and immunosuppressants aggravate αGIs-induced PI. Conservative therapy is recommended when treating αGIs-induced PI. [ABSTRACT FROM AUTHOR]

Aims: Sodium glucose co‐transporter 2 inhibitors have diuretic effects in both patients with glycosuria and with natriuresis. We sought to assess the effect of luseogliflozin on estimated plasma volume (ePV) in patients with type 2 diabetes and heart failure with preserved ejection fraction (HFpEF). Methods and results: This study was a post‐hoc analysis of the MUSCAT‐HF trial (UMIN000018395), a multicentre, prospective, open‐label, randomized controlled trial that assessed the effect of 12 weeks of luseogliflozin (2.5 mg, once daily, n = 83) as compared with voglibose (0.2 mg, three times daily, n = 82) on the reduction in brain natriuretic peptide (BNP) in patients with type 2 diabetes and HFpEF. The analysis compared the change in ePV calculated by the Straus formula from baseline to Weeks 4, 12, and 24, using a mixed‐effects model for repeated measures. We also estimated the association between changes in ePV and changes in other clinical parameters, including BNP levels. Luseogliflozin significantly reduced ePV as compared to voglibose at Week 4 {adjusted mean group‐difference −6.43% [95% confidence interval (CI): −9.11 to −3.74]}, at Week 12 [−8.73% (95%CI: −11.40 to −6.05)], and at Week 24 [−11.02% (95%CI: −13.71 to −8.33)]. The effect of luseogliflozin on these parameters was mostly consistent across various patient clinical characteristics. The change in ePV at Week 12 was significantly associated with log‐transformed BNP (r = 0.197, P = 0.015) and left atrial volume index (r = 0.283, P = 0.019). Conclusions: Luseogliflozin significantly reduced ePV in patients with type 2 diabetes and HFpEF, as compared with voglibose. The reduction of intravascular volume by luseogliflozin may provide clinical benefits to patients with type 2 diabetes and HFpEF. [ABSTRACT FROM AUTHOR]

Background: The TCF7L2-gene (TCF7L2; Transcription factor 7-like 2) involves in regulation of cellular proliferation and differentiation. It also increased risk for type 2 diabetes (T2D), dose effect were reported for the rs7903146 variant. The risk alleles of TCF7L2 gene involves in progression of impaired glucose tolerance to diabetes prospectively and an increased severity of the disease Material and Methods: Prospective, randomised study. Combination of Metformin, Glimepride Voglibose has been prescribed in TCF7L2 gene associated type 2 diabetes mellitus patients s Results: TCF7L2 gene is associated with Type 2 diabetes mellitus. Genetic investigation was done in all 40 patients three genotypes have been identified 10 patients were on CC, 12 patients were on CT and 18 patients were on TT genotypes. Baseline values are higher in TT genotype when compared with CT & CC genotypes. There were significant improvement in blood glucose levels were as a controlled lipid profile was observed in CC genotype but no significant was observed in CT, TT and in group Conclusion: Patients HbA1c ranges from <9.0 - 9.5 % prescribed with triple drug combination therapy of metformin, Glimepride, voglibose shows significant improvement in blood glucose levels in all three genotypes but no significant was observed in CT, TT genotypes. As a result combination of triple drug combination therapy of metformin with glimepride, voglibose is the better drug of choice in CC genotype associated type 2 diabetes mellitus after 3 months of treatment. [ABSTRACT FROM AUTHOR]

BackgroundCombination 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.MethodsA 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.ResultsThe reduction in the levels of HbA1c was −1.62%±0.07% in the vogmet group and −1.31%±0.07% in the metformin group (P=0.003), and significantly more vogmet-treated patients achieved the target HbA1c levels of

Chronic hyperglycemia induces activation of the polyol‐sorbitol pathway, which is a major contributor to microvascular complications like stroke. The current study was designed to elucidate the therapeutic role of α‐glucose inhibitor in chronic hyperglycemia‐induced impaired polyol pathway and associated micro‐complications. Male albino‐Wistar rats (200–250 g) were treated with voglibose 10 mg kg−1 day−1/p.o. for 2 weeks before middle cerebral artery occlusion; 72 hr after surgery, neurological score was evaluated and blood was collected for the assessment of various serum biochemical parameters like CRP, CK‐MB, LDH, lipid profile, and blood glucose levels. In the end, brain samples were excised for determination of brain infarct volume, brain hemisphere weight difference, Na+‐K+ ATPase activity oxidative stress‐related parameters, aldose reductase activity, and gene expression studies. Results from the present study indicate that pre‐treatment with voglibose showed significant improvement in lipid parameters but did not impact glucose levels. Voglibose has shown a statistically significant (p <.05) reduction in neurological score and brain infarct volume, and the difference in brain hemisphere weight as compared to the disease control group. Voglibose significantly (p <.05) improve all biochemical parameters and reduced Na+‐K+ ATPase and aldose reductase activity. Moreover, voglibose produced a significant reduction in oxidative stress and down‐regulation of TNF‐α and BCl‐2 gene expression which reduces the risk of factors related to stroke. In conclusion, the pleiotropic effect of voglibose on cerebrovascular complications may be due to inhibition of aldose reductase or anti‐inflammatory pathways. [ABSTRACT FROM AUTHOR]

The present study was aimed to compare the efficacy of metformin 500mg + glimepiride 1mg combination with metformin 500mg+ glimepiride 1mg+ voglibose 0.2mg combination in type 2 diabetes mellitus patients. The primary objective of the study is to compare the efficacy of double drug (metformin & glimepiride) versus triple drug therapy (metformin, glimepiride and voglibose) in type 2 diabetes mellitus subjects and secondary objective is to quantify their effect on glycated haemoglobin (HbA1c) levels in diabetic patient. A total of 100 type-2 diabetic patients were included in the study after obtaining the patient's consent and institutional ethics approval. The study was designed as prospective, nonrandomized, two-arm trial. One hundred type 2 diabetic patients after satisfying the inclusion criteria were included in the study and divided in two groups of 50 each as Group A and Group B. Group A patients received metformin 500mg + glimepiride 1mg, and Group B patients received metformin 500mg + glimepiride 1mg + voglibose 0.2mg. The patient blood samples were analysed for HBA1c, blood sugar levels, serum urea and creatinine during the trial initiation and other follow-ups in 3 months (day0, day15, day30, day45, day60, day75, day90). The obtained data was analysed using chi-square test for non-parametric data and student t-test for parametric data. A significant change in mean HbA1c levels (p value-0.0001) were observed in Group A and Group B patients between the baseline values (7.3±1.4 & 9.7±1.2) and after 3 months treatment values (6.9±1.4 & 7.8±1.1). While comparing the mean HbA1c levels between Group A and Group B after three months of treatment, it was >7.5% in group B patients. No significant effect was seen on serum blood urea of group A and B patients. Triple drug intensification of metformin 500mg with glimepiride 1mg and voglibose 0.2mg showed significant decrease in HbA1c levels during three months of treatment. Further observational studies may be required to provide prolonged treatment data of this combination. [ABSTRACT FROM AUTHOR]

The main aim of the research is to establish a simple, economical, responsive HPLC system in which teneligliptin, metformin and voglibose can be combined simultaneously. Analysis was conducted using the Methanol: water (65:35v/v) mobile stage at pH 3 with a cosmosil C18 column (250mm x 4.6Id, particle size: 5µ). The detection took place at the flow rate of 232nm, 0.8ml/min. Metformin, Voglibose and Teneligliptin were respectively 4.4min, 5.8min, 6.9min. Linearity levels for MET, VOG were found to be between 250-1250 µg/ml and TEN were 0,1-0,5 µg/ml. It was identified that the percentages for MET, VOG & TEN were 99.84%, 100.24%, 99.94%. Detection limits have been found for MET, VOG & TEN, 0.99ug/ml, 0.001ug/ml, 0.10ug/ml respectively for MET, VOG and TEN. The quantitation limits for MET, VOG, and TEN respectively were 2.87 ug/ml, 0.0042 U/ml, 0.332 ug/ml. In acidic, alkaline, oxidative, photolytic and thermal conditions, the strengthdegradation analysis was conducted according to ICH guidelines. The approach has been successfully tested and found to be within the limit for all parameters. The method developed has been tested for linearity, precision, accuracy, device suitability and can be used effectively for quality control analysis according to ICH guidelines. [ABSTRACT FROM AUTHOR]

An alpha-glucosidase inhibitor Voglibose is used for lowering blood glucose levels in people with diabetes A very straight forward, quick, responsive and accurate UV-Spectrophotometric method of analysis have been developed for assessment of Voglibose in pharmaceutical formulation. Since Voglibose only absorbs UV in the low wavelength area, it cannot be identify with high sensitivity. Voglibose has shown successful results for various analytical instruments only in the permutation of Taurine and Sodium periodate. The API was derivatives using Taurine and Sodium periodate in water and methanol. Drug exhibited distinct λmax in methanol at 281nm. Linearity was observed in the concentration range 10-80 µg/ml. The method was validated by recovery studies. The methods used are inexpensive and sensitive for the inference of Voglibose in bulk drug and tablet dosage forms. [ABSTRACT FROM AUTHOR]

Purpose: To determine the effect of Voglibose add-on therapy on daily glycemic excursions (using FreeStyle® Libre Pro™, a Flash glucose monitoring system) in Indian patients with type 2 diabetes mellitus (T2DM) receiving a stable dose of metformin (Met) or metformin+sulfonylurea (Met+SU). Patients and Methods: T2DM patients with glycosylated hemoglobin (HbA1c) ≥7.0% and at least two postprandial excursions ≥140 mg/dL (within 2 h of meal) during the screening phase (visit 1/day -14 ± 2) were enrolled in this prospective, multicenter interventional study. The patients were randomized at visit 2 (day 0 ± 2) to receive Voglibose 0.2 or 0.3 mg tablets (BID/TID) as add-on therapy to Met and Met+SU. All the patients were followed at day 14 ± 2 (visit 3), month 3 ± 14 days (visit 4), 14 weeks (i.e., visit 4 + 14 days) ±2 days (visit 5), and month 6 ± 14 days (visit 6). Continuous glucose monitoring was performed to study glycemic excursions at visits 2, 3, and 5. The study outcomes were: change in average number of glycemic excursions per day, percent time spent in glucose fluctuations, mean Postprandial glucose (PPG), Fasting plasma glucose (FPG), day and night time mean glucose levels from baseline to day 14 and week 14; change in mean amplitude of glycemic excursion (MAGE) from baseline to 14 weeks; and mean HbA1c level at 3 and 6 months. Results: Out of 110 patients enrolled, 101 patients (91.8%) (Met+SU+Voglibose: 73 and Met+Voglibose: 28) completed the study. There was a significant decrease in average number of glycemic excursions per day from baseline to day 14 in the Met+Sul+Voglibose group and to week 14 in the Met+Voglibose group. There was also a significant reduction in percent time spent above target glucose range from baseline to day 14 in both treatment groups and to week 14 in the Met+SU+Voglibose group. A significant reduction in mean PPG area under the curve, day and night time mean glucose levels, and mean FPG levels from baseline to day 14 was reported in both treatment groups. A significant reduction in night time glucose, and average MAGE and HbA1c levels was reported from baseline to week 14 in the Met+Voglibose group and the Met+SU+Voglibose group, respectively. At 6 months, body weight, glucose levels, cholesterol, low-density lipoprotein-cholesterol, and HbA1c were significantly lower, especially in the Met+SU+Voglibose arm. Conclusion: Voglibose was useful in reducing glycemic variability and improving glycemic control in Asian Indian adults with T2DM. (CTRI/2018/04/013074). [ABSTRACT FROM AUTHOR]

Background: Voglibose, an a-glucosidase inhibitor, inhibits breakdown of complex carbohydrates into simple sugar units in intestine. Studies showed that voglibose metabolism in the liver might be negligible due to its poor intestinal absorption. Numerous microorganisms live in intestine and have several roles in metabolism and detoxification of various xenobiotics. Due to the limited information, the possible metabolism of voglibose by intestinal microbiota was investigated in vitro and in vivo. Methods: For the in vitro study, different concentrations of voglibose were incubated with intestinal contents, prepared from both vehicle- and antibiotics-treated mice, to determine the decreased amount of voglibose over time by using liquid chromatographymass spectrometry. Similarly, in vivo pharmacodynamic effect of voglibose was determined following the administration of voglibose and starch in vehicle- and antibiotic-pretreated non-diabetic and diabetic mice, by measuring the modulatory effects of voglibose on blood glucose levels. Results: The in vitro results indicated that the remaining voglibose could be significantly decreased when incubated with the intestinal contents from normal mice compared to those from antibiotic-treated mice, which had less enzyme activities. The in vivo results showed that the antibiotic pretreatment resulted in reduced metabolism of voglibose. This significantly lowered blood glucose levels in antibiotic-pretreated mice compared to the control animals. Conclusion: The present results indicate that voglibose would be metabolized by the intestinal microbiota, and that this metabolism might be pharmacodynamically critical in lowering blood glucose levels in mice. [ABSTRACT FROM AUTHOR]

In this research, a sensitive fluorometric and colorimetric dual-mode sensing platform based on nitrogen-doped carbon quantum dots (NCDs) and magnetic Fe nanoparticles with peroxidase-like activity (Fe nanozymes, Fe NZs) was established, and was further applied for the detection of α-glucosidase (α-glu) and its inhibitors. The ⋅OH that produced by H 2 O 2 catalyzed by Fe NZs can oxidize the colorless diammonium 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonate) (ABTS) to green oxABTS, and a noticeable absorption peak at 417 nm appeared. Simultaneously, oxABTS can quench the fluorescence of NCDs at 402 nm via fluorescence resonance energy transfer (FRET). 2-O-α-D-glucopyranosyl-L-ascorbic acid (AAG) can be decomposed by α-glu to glucose and ascorbic acid (AA), AA can prevent the oxidation of ABTS, resulting in the absorption at 417 nm decreased. Moreover, the quenching effect of oxABTS on NCDs is weakened, and the fluorescence at 402 nm is restored. Therefore, based on the change of absorption at 417 nm and fluorescence at 402 nm, the fluorometric and colorimetric dual-mode sensing method can be used for the determination of acarbose and voglibose that are the inhibitors of α-glu. [Display omitted] • The NCDs and Fe NZs were synthesized by low-cost precursors with simple and safe procedure. • A dual-mode (colorimetric/fluorometric) detection method for α-glucosidase was developed. • The dual-mode (colorimetric/fluorometric) sensing platform displayed a sensitive response to α-glucosidase and afforded a low limit of detection. • The dual-mode sensing platform was also successfully applied in acarbose screening that was the α-glucosidase inhibitors. [ABSTRACT FROM AUTHOR]

Abstract Background Pneumatosis intestinalis (PI) is a rare condition characterized by the presence of gas within the gastrointestinal tract wall. Most cases of PI have a benign clinical course, although some have serious outcomes. Mechanical stress on or bacterial infection of the gastrointestinal tract wall may be responsible for the onset of PI, but the detailed mechanism of PI pathogenesis is still unclear. Here, we describe two Japanese patients presenting with benign PI. Case presentation Case 1, a 37-year-old previously healthy male patient, had a 1-week history of abdominal pain, and case 2, a 78-year-old female diabetic patient, had a 2-week history of voglibose treatment and abdominal pain. Intramural gas was mainly distributed in the colon in case 1 and in the small intestine in case 2. Interestingly, neither patient showed obvious inflammatory signs upon admission and recovered spontaneously with conservative treatment, including fasting and fluid infusion without antibiotics. Voglibose treatment was terminated in case 2. Recent studies have shown the presence of nonpathogenic bacteria, such as Clostridium spp., in PI lesions, which usually play an important role in modulating the tolerance of the gastrointestinal immune responses. The benign clinical course and spontaneous resolution of PI in these patients, without specific treatment, suggests that nonpathogenic indigenous bacteria in the gastrointestinal tract participate in the pathogenesis of PI. Conclusion In patients with benign PI, the absence of an inflammatory response and the spontaneous resolution of the disease without specific treatment suggest the participation of nonpathogenic indigenous bacteria of the gastrointestinal tract.

OBJECTIVE: 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). METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Objective This study aimed to evaluate and analyze the characteristics of Indian patients with type 2 diabetes mellitus (T2DM) in relation to the usage patterns of a fixed-dose combination (FDC) of glimepiride, metformin, and voglibose. Methods This retrospective, observational, multicentric analysis was conducted from March 2021 to September 2022. It involved adult patients (aged ≥18 years) with T2DM from 424 sites including a combination of hospitals and privately owned clinics across India to ensure comprehensive representation of the patient population The study included patients who had been treated with FDC of glimepiride, metformin, and voglibose of varying strengths for T2DM management. Data were collected through a pre-designed electronic form, which captured demographic details, medical history, T2DM history, and drug usage patterns from medical records. The collected data were then analyzed using descriptive statistical methods. Results This analysis encompassed a final cohort of 8,587 patients out of which 5,840 were males with a mean age of 54.91 years and a BMI of 28.41 kg/m 2 . Newly diagnosed T2DM cases were 35.23%, 54.79% had a family history, and 61.21% had risk factors such as smoking, sedentary lifestyle, and others. Dyslipidemia (13.94%) and neuropathy (14.48%) were common comorbidities. The most prescribed FDC was 1 mg glimepiride, 500 mg metformin, 0.2 mg voglibose (40.14%), the most preferred dosing frequency was once daily (52.92%) and the most common duration of treatment was one to three months (48.78%). Conclusion In routine Indian clinical practice, the triple drug FDC of 1 mg glimepiride, 500 mg metformin, and 0.2 mg voglibose, taken once daily for one to three months, was the most common treatment for both newly diagnosed and long-standing diabetes patients., Competing Interests: The authors have declared financial relationships, which are detailed in the next section., (Copyright © 2024, Shamanna et al.)

Aim: By keeping in aspects, the pharmacological potential of heterocyclic compounds, pyrimidine-based compounds were designed, synthesized and evaluated for α-amylase inhibitory potential. Materials & methods: Five new series 1a-l, 2a-d, 3a-d, 4a-d and 5a-d of 1,2,3,4-tetrahydroprimidine-5-carboxylate derivatives were designed by de novo method by taking Alogliptin as reference compound. Here in we describe synthesis and characterization of compounds as potential α-amylase inhibitor. Results: Structure activity relationship (SAR), in vitro analysis and molecular modelling approaches generate compounds 1 h, 1i, 1k and 4c as potential lead with good α-amylase inhibitory selection. However, compound 1k failed the criteria of optimization as drug lead by ADME studies while all other compounds showed optimum range for all in silico ADME parameters. Conclusion: Therefore, these compounds can serve as potential lead candidate in developing anti-diabetic therapy.

The alpha-glucosidase inhibitor voglibose (VO) was recently reported to have a protective effect against weight gain as well as affect various metabolic changes related to food intake and gut–brain signaling. We hypothesized that VO prevents weight gain by altering neurometabolome profiles in the hypothalamus to reduce food intake. To test this hypothesis, we assessed metabolite profiles in the hypothalamus of standard diet- or high-fat (HF) diet-fed mice in the absence or presence of VO. In total, 29 male C57BL/6 mice were divided into 3 groups: (1) lean control, (2) HF, and (3) HF + VO. Vehicle or VO was administered for 12 weeks. The results showed that there were alterations in levels of metabolites across several metabolic pathways in the hypothalamus. VO treatment increased levels of many amino acids including arginine, glutamine, histidine, isoleucine, leucine, methionine, phenylalanine, proline, serine, threonine, tryptophan, tyrosine, and valine in the hypothalamus. In addition, levels of 2-hydroxy-2-methyl-butyric acid in the hypothalamus were significantly increased after VO administration in HF diet-fed mice. Among lipid metabolites, levels of fatty acids were higher in the hypothalamus of VO-treated mice than in that of HF diet-fed mice. In terms of the energy status, the ATP/ADP ratio was higher in the hypothalamus of VO-treated mice (P < 0.001), thereby indicating an energy surplus. In conclusion, VO supplementation altered metabolite profiles in the hypothalamus to enhance catabolism, which is possibly responsible for the hypophagic effect of VO in HF diet-fed mice. [ABSTRACT FROM AUTHOR]

Background: ADA has cut-off value for IGT (140-200 mg/dL) but has a lower cut-off value for IFG (100-125 mg/dL) and has additional hemoglobin A1c (HbA1c) based criteria of a level of 5.7% to 6.4% for the definition of prediabetes. Due to progressive nature of prediabetes, dual drug therapy produces additive effects, allows the use of submaximal doses, and less side effects of individual agents. Therefore, the present study was designed to study the effect of voglibose in comparison to pioglitazone on glycemic control as an add-on drug in prediabetes patients whose glycemic status was uncontrolled with metformin alone. Methods: The present study was open, randomized, parallel group comparison of two active treatment groups over a period of six months. Sixty-seven patients of either sex in the age group of 30-60 years, suffering from prediabetes, with FBG: 100-125 mg/dl and PPBG:140-200 mg/dl as per ADA were selected at randomly. The effect of FDC of Voglibose with Metformin and Pioglitazone with Metformin were observed on various parameters of Glycemic Triad (FBG, PPBG, HOMA-IR, HbA1c and Serum Insulin). Results: At the end of 6 months it was observed that though both FDC of Voglibose with Metformin and Pioglitazone with Metformin reduced Glycaemia Statistically significantly but Pioglitazone with Metformin caused a significantly greater percentage change in Glycaemia as compared with Voglibose with Metformin. Few side effects were observed with Voglibose but not with Pioglitazone. Conclusions: Though Voglibose with Metformin and Pioglitazone with Metformin were equally effective in lowering Glycemia yet Pioglitazone with Metformin showed better results in improving glycaemia, as compared to Voglibose with Metformin. Pioglitazone with Metfo rmin had minimal side effects as compared to Voglibose with Metformin [ABSTRACT FROM AUTHOR]