Explore the vast range of titles available.

Early treatment intensification leading to sustained good glycaemic control is essential to delay diabetic complications. Although initial combination therapy has been suggested to offer more opportunities than a traditional stepwise approach, its validity remains to be determined. Vildagliptin Efficacy in combination with metfoRmIn For earlY treatment of type 2 diabetes (VERIFY) was a randomised, double-blind, parallel-group study of newly diagnosed patients with type 2 diabetes conducted in 254 centres across 34 countries. The study consisted of a 2-week screening visit, a 3-week metformin-alone run-in period, and a 5-year treatment period, which was further split into study periods 1, 2, and 3. Patients aged 18–70 years were included if they had type 2 diabetes diagnosed within 2 years prior to enrolment, and centrally confirmed glycated haemoglobin A1c (HbA1c) of 48–58 mmol/mol (6·5–7·5%) and a body-mass index of 22–40 kg/m2. Patients were randomly assigned in a 1:1 ratio either to the early combination treatment group or to the initial metformin monotherapy group, with the help of an interactive response technology system and simple randomisation without stratification. Patients, investigators, clinical staff performing the assessments, and data analysts were masked to treatment allocation. In study period 1, patients received either the early combination treatment with metformin (stable daily dose of 1000 mg, 1500 mg, or 2000 mg) and vildagliptin 50 mg twice daily, or standard-of-care initial metformin monotherapy (stable daily dose of 1000 mg, 1500 mg, or 2000 mg) and placebo twice daily. If the initial treatment did not maintain HbA1c below 53 mmol/mol (7·0%), confirmed at two consecutive scheduled visits which were 13 weeks apart, patients in the metformin monotherapy group received vildagliptin 50 mg twice daily in place of the placebo and entered study period 2, during which all patients received the combination therapy. The primary efficacy endpoint was the time from randomisation to initial treatment failure, defined as HbA1c measurement of at least 53 mmol/mol (7·0%) at two consecutive scheduled visits, 13 weeks apart from randomisation through period 1. The full analysis set included patients who received at least one randomised study medication and had at least one post-randomisation efficacy parameter assessed. The safety analysis set included all patients who received at least one dose of randomised study medication. This study is registered with ClinicalTrials.gov, NCT01528254. Trial enrolment began on March 30, 2012, and was completed on April 10, 2014. Of the 4524 participants screened, 2001 eligible participants were randomly assigned to either the early combination treatment group (n=998) or the initial metformin monotherapy group (n=1003). A total of 1598 (79·9%) patients completed the 5-year study: 811 (81·3%) in the early combination therapy group and 787 (78·5%) in the monotherapy group. The incidence of initial treatment failure during period 1 was 429 (43·6%) patients in the combination treatment group and 614 (62·1%) patients in the monotherapy group. The median observed time to treatment failure in the monotherapy group was 36·1 (IQR 15·3–not reached [NR]) months, while the median time to treatment failure time for those receiving early combination therapy could only be estimated to be beyond the study duration at 61·9 (29·9–NR) months. A significant reduction in the relative risk for time to initial treatment failure was observed in the early combination treatment group compared with the monotherapy group over the 5-year study duration (hazard ratio 0·51 [95% CI 0·45–0·58]; p<0·0001). Both treatment approaches were safe and well tolerated, with no unexpected or new safety findings, and no deaths related to study treatment. Early intervention with a combination therapy of vildagliptin plus metformin provides greater and durable long-term benefits compared with the current standard-of-care initial metformin monotherapy for patients with newly diagnosed type 2 diabetes. Novartis.

Bullous pemphigoid (BP) is an organ-specific autoantibody-mediated blistering skin disease that mainly affects the elderly. Typical clinical features include the widespread blisters, often preceded by and/or associated with itchy urticarial or eczema-like lesions. BP patients have circulating autoantibodies against BP180 and/or the plakin family protein BP230 both of which are components of hemidesmosomes in basal keratinocytes. Most BP autoantibodies particularly target the epitopes within the non-collagenous NC16A domain of BP180. Clinical findings and murine models of BP have provided evidence of a pathogenic role of anti-NC16A autoantibodies. However, it is largely unknown what triggers the breakage of immunotolerance against BP180 in elderly individuals. The incidence of BP has been increased over the past two decades in several countries. Aside from aging populations, the factors behind this phenomenon are still not fully understood. Neurodegenerative diseases such as multiple sclerosis, Parkinson's disease, and certain dementias are independent risk factors for BP. Recently several case reports have described BP in patients with diabetes mellitus (DM) patients who have been treated with dipeptidyl peptidase-4 inhibitors (DPP-4i or gliptins), which are a widely used class of anti-DM drugs. The association between the use of DPP-4is, particularly vildagliptin, and BP risk has been confirmed by several epidemiological studies. Evidence suggests that cases of gliptin-associated BP in Japan display certain features that set them apart from cases of \"regular\" BP. These include a \"non-inflammatory\" phenotype, targeting by antibodies of different immunodominant BP180 epitopes, and a specific association with the human leukocyte antigen (HLA) types. However, recent studies in European populations have found no major differences between the clinical and immunological characteristics of gliptin-associated BP and \"regular\" BP. The DPP-4 protein (also known as CD26) is ubiquitously expressed and has multiple functions in various cell types. The different effects of the inhibition of DPP-4/CD26 activity include, for example, tissue modeling and regulation of inflammatory cells such as T lymphocytes. Although the pathomechanism of gliptin-associated BP is currently largely unknown, investigation of the unique effect of gliptins in the induction of BP may provide a novel route to better understanding of how immunotolerance against BP180 breaks down in BP.

Diabetes mellitus (DM) is a rapidly prevailing disease throughout the world that poses boundless risk factors linked to several health problems. Vildagliptin is the standard dipeptidyl peptidase-4 (DPP-4) inhibitor type of medication that is used for the treatment of diabetes anti-hyperglycemic agent (anti-diabetic drug). The current study aimed to synthesize vildagliptin-loaded ZnO NPs for enhanced efficacy in terms of increased retention time minimizing side effects and increased hypoglycemic effects. Herein, Zinc Oxide (ZnO) nanoparticles (NPs) were constructed by precipitation method then the drug vildagliptin was loaded and drug loading efficiency was estimated by the HPLC method. X-ray diffraction analysis (XRD), UV–vis spectroscopy, FT-IR, scanning electron microscope (SEM), and EDX analysis were performed for the characterization of synthesized vildagliptin-loaded ZnO NPs. The UV–visible spectrum shows a distinct peak at 363 nm which confirms the creation of ZnO NPs and SEM showed mono-dispersed sphere-shaped NPs. EDX analysis shows the presence of desired elements along with the elemental composition. The physio-sorption studies, which used adsorption isotherms to assess adsorption capabilities, found that the Freundlich isotherm model explains the data very well and fits best. The maximum adsorption efficiency of 58.83% was obtained. Further, In vitro, anti-diabetic activity was evaluated by determining the α-amylase and DPP IV inhibition activity of the product formed. The formulation gave maximum inhibition of 82.06% and 94.73% of α-amylase and DPP IV respectively. While at 1000 µg/ml concentration with IC 50 values of 24.11 μg/per ml and 42.94 μg/ml. The inhibition of α-amylase can be ascribed to the interactive effect of ZnO NPs and vildagliptin.

Three rapid, accurate, and ecofriendly processed spectrophotometric methods were validated for the concurrent quantification of remogliflozin (RGE) and vildagliptin (VGN) from formulations using water as dilution solvent. The three methods developed were based on the calculation of the peak height of the first derivative absorption spectra at zero-crossing points, the peak amplitude difference at selected wavelengths of the peak and valley of the ratio spectra, and the peak height of the ratio first derivative spectra. All three methods were validated adapting the ICH regulations. Both the analytes showed a worthy linearity in the concentration of 1 to 60 µg/mL and 2 to 90 µg/mL for VGN and RGE, respectively, with an exceptional regression coefficient (r2 ≥ 0.999). The developed methods demonstrated an excellent recovery (98.00% to 102%), a lower percent relative standard deviation, and a relative error (less than ±2%), confirming the specificity, precision, and accuracy of the proposed methods. In addition, validated spectrophotometric methods were commendably employed for the simultaneous determination of VGN and RGE from solutions prepared in the laboratory and the formulation. Hence, these methods can be utilized for the routine quality control study of the pharmaceutical preparations of VGN and RGE in pharmaceutical industries and laboratories. The ecofriendly nature of the anticipated spectrophotometric procedures was confirmed by the evaluation of the greenness profile by a semi-quantitative method and the quantitative and qualitative green analytical procedure index (GAPI) method.

Aims/hypothesisThe use of oral glucose-lowering drugs, particularly those designed to target the gut ecosystem, is often observed in association with altered gut microbial composition or functional capacity in individuals with type 2 diabetes. The gut microbiota, in turn, plays crucial roles in the modulation of drug efficacy. We aimed to assess the impacts of acarbose and vildagliptin on human gut microbiota and the relationships between pre-treatment gut microbiota and therapeutic responses.MethodsThis was a randomised, open-labelled, two-arm trial in treatment-naive type 2 diabetes patients conducted in Beijing between December 2016 and December 2017. One hundred participants with overweight/obesity and newly diagnosed type 2 diabetes were recruited from the Pinggu Hospital and randomly assigned to the acarbose (n=50) or vildagliptin (n=50) group using sealed envelopes. The treatment period was 6 months. Blood, faecal samples and visceral fat data from computed tomography images were collected before and after treatments to measure therapeutic outcomes and gut microbiota. Metagenomic datasets from a previous type 2 diabetes cohort receiving acarbose or glipizide for 3 months were downloaded and processed. Statistical analyses were applied to identify the treatment-related changes in clinical variables, gut microbiota and associations.ResultsNinety-two participants were analysed. After 6 months of acarbose (n=44) or vildagliptin (n=48) monotherapy, both groups achieved significant reductions in HbA1c (from 60 to 46 mmol/mol [from 7.65% to 6.40%] in the acarbose group and from 59 to 44 mmol/mol [from 7.55% to 6.20%] in the vildagliptin group) and visceral fat areas (all adjusted p values for pre–post comparisons <0.05). Both arms showed drug-specific and shared changes in relative abundances of multiple gut microbial species and pathways, especially the common reductions in Bacteroidetes species. Three months and 6 months of acarbose-induced changes in microbial composition were highly similar in type 2 diabetes patients from the two independent studies. Vildagliptin treatment significantly enhanced fasting active glucagon-like peptide-1 (GLP-1) levels. Baseline gut microbiota, rather than baseline GLP-1 levels, were strongly associated with GLP-1 response to vildagliptin, and to a lesser extent with GLP-1 response to acarbose.Conclusions/interpretationThis study reveals common microbial responses in type 2 diabetes patients treated with two glucose-lowering drugs targeting the gut differently and acceptable performance of baseline gut microbiota in classifying individuals with different GLP-1 responses to vildagliptin. Our findings highlight bidirectional interactions between gut microbiota and glucose-lowering drugs.Trial registrationClinicalTrials.gov NCT02999841FundingNational Key Research and Development Project: 2016YFC1304901.

BACKGROUND: Dipeptidyl peptidase 4 (DPP-4) inhibitors are primarily excreted renally. Linagliptin is an exception with excretion primarily through enterohepatic system and is expected to have a better renal profile, though real-world data are scarce. Comparative studies on the renal safety and glycaemic control with linagliptin versus popular DPP-4 inhibitors such as vildagliptin are crucial, especially in the background of COVID-19 pandemic that hugely impacted glycemic control in India's large type 2 diabetes mellitus (T2DM) population. MATERIALS AND METHODS: Adult T2DM patients not controlled with metformin alone, added linagliptin (5 mg once daily) or vildagliptin (50 mg twice daily) in the tertiary care outpatient department setting were included in the study. Parameters such as glycosylated hemoglobin, fasting blood glucose, postprandial blood glucose, blood urea nitrogen, serum creatinine, estimated glomerular filtration rate (eGFR), change in renal function, glycemic control, and clinical parameters were compared at baseline, 2 months, and 6 months of treatment. All adverse events were analyzed using the WHO-UMC scale. RESULTS: Both groups achieved similar glycemic control, however, accompanied with impairment of renal parameters after 6 months. Compared to linagliptin, almost 300% rise in creatinine and 140% fall in eGFR were noted in the vildagliptin recipients. However, the difference in serum creatinine or eGFR could not attain statistical significance in the study. CONCLUSION: Both linagliptin and vildagliptin can help to achieve glycemic control despite possible influence of the COVID-19 pandemic and are generally well tolerated. However, renal functions are better preserved with linagliptin. Further studies involving a larger sample size and longer follow-up are recommended before generalization of the findings of the present study.

Vildagliptin is a representative of Dipeptidyl Peptidase-4 (DPP-4) inhibitors, antihyperglycemic drugs, approved for use as monotherapy and combination therapy in type 2 diabetes mellitus. By inhibiting enzymatic decomposition, DPP-4 inhibitors increase the half-life of incretins such as GLP-1 (Glucagon-like peptide-1) and GIP (Gastric inhibitors polypeptide) and prolong their action. Some studies present results suggesting the anti-sclerotic and vasculoprotective effects of vildagliptin reaching beyond glycemic control. Vildagliptin is able to limit inflammation by suppression of the NF-κB (nuclear factor kappa-light-chain-enhancer of activated B cells) signaling pathway and proinflammatory agents such as TNF-α (tumor necrosis factor α), IL-1β (Interleukin-1β), and IL-8 (Interleukin 8). Moreover, vildagliptin regulates lipid metabolism; attenuates postprandial hypertriglyceridemia; and lowers serum triglycerides, apolipoprotein B, and blood total cholesterol levels. This DPP-4 inhibitor also reduces macrophage foam cell formation, which plays a key role in atheromatous plaque formation and stability. Vildagliptin reduces vascular stiffness via elevation of nitric oxide synthesis, improves vascular relaxation, and results in reduction in both systolic and diastolic blood pressure. Treatment with vildagliptin lowers the level of PAI-1 presenting possible antithrombotic effect. By affecting the endothelium, inflammation, and lipid metabolism, vildagliptin may affect the development of atherosclerosis at its various stages. The article presents a summary of the studies assessing vasculoprotective effects of vildagliptin with special emphasis on atherogenesis.

Vildagliptin is one of the dipeptidyl peptidase-4 (DPP-4) inhibitors that have been shown to improve hyperglycemia in clinical trials among patients with type 2 diabetes. However, few studies have examined the efficacy of vildagliptin in patients with diabetic kidney disease (DKD). Eight patients with DKD received oral vildagliptin 50-100 mg/day. The duration of diabetes was 6.7±5.9 years and observation period was 23.6±9.8 months. Changes in fasting blood glucose, and hemoglobin A1c (HbA1c), estimated glomerular filtration rate (eGFR), and urine protein-to-creatinine ratio (UPCR) were studied before and after the administration of vildagliptin. Vildagliptin treatment significantly decreased fasting blood glucose and HbA1c, compared to baseline (132±56 mg/dl, p=0.036, 6.0±0.3, p=0.041, respectively). UPCR tended to be decreased, albeit without statistical significance. However, eGFR was decreased after the administration of vildagliptin. No significant adverse effects were observed in all patients during the study. Although the sample size was limited and the observation period was brief, vildagliptin was found to be an effective and reasonably well-tolerated treatment for patients with DKD.

In this work, we present a novel method for determining the prescribed dosages of Dapagliflozin (DAPA), Vildagliptin (VIL), and Metformin (MET) all at once. The goal of this research is to create and test a new RP-HPLC technique that can simultaneously measure DAPA, VIL, and MET in formulation and bulk materials.The goal of this research is to create and test a new RP-HPLC technique that can simultaneously measure DAPA, VIL, and MET in formulation and bulk materials. An isocratic elution method was used with a flow rate of 1.0 ml min-1 and a diode array detector operating at 261nm to perform the chromatographic separation on a kromasil-C18 column(4.5 x 250mm; 5µm). Using orthophosphoric acid to get the pH down to 3.5, the mobile phase consisted of a combination of 0.05 mmol potassium dihydrogen phosphate buffer and acetonitrile in an 80:20 v/v ratio. With concentrations ranging from 0.1-1.0µg/ml and 2-25µg/ml, as well as DAPA, VIL, and MET values from 10 to 120µg/ml, the calibration curve displayed linearity. The research found that DAPA had a limit of detection and quantification of 0.0122µg/ml while VIL had a limit of 0.0323µg/ml. The upper limits for MET were 0.232µg/ml and 0.635µg/ml, while the lower limits were 1.124µg/ml and 3.124µg/ml, respectively. We have developed and validated a new reversed-phase high-performance liquid chromatography (RP-HPLC) method for the quantitative determination of vildagliptin and metformin. This method is very sensitive, easy to use, and stable. The suggested technique could be used to routinely measure DAPA, VIL, and MET.

In Tunisia, bioequivalence studies have been required for generic drug approval since 2008. This study aimed to assess the bioequivalence of vildagliptin and metformin fixed-dose combination (FDC) 850/50 mg for a tested (Bi-Galvine) versus the approved reference products (Galvumet). A randomized, two-way, two-period, single oral dose, open-label, crossover, bioequivalence study with a washout period of 7 days to compare metformin/vildagliptin film-coated tablets in 18 healthy Tunisian subjects aged between 18 and 50 years under fed conditions was conducted at the National Center Chalbi Belkahia of Pharmacovigilance. During each period, 20 blood samples were collected from each subject at pre-dosing (0.00) and between 0.25 and 24.00 h after dosing. The bioequivalence between the test (T) and reference (R) products required 90% confidence intervals (CIs) for the geometric least square (LS) mean T/R ratio to be within 80–125% for the pharmacokinetic parameters, maximum plasma concentration (C max ), and Area Under the Curve from zero to 24 h (AUC 0–24 h ). The 90% CIs of the geometric means of the T/R ratios for C max and AUC 0–24 h for metformin were 92.01–102.66% and 93.55–101.80%, respectively; the corresponding results for vildagliptin were 96.03–107.09% and 94.46–101.92%, respectively. Other parameters, such as AUC 0-∞ , time to maximum concentration (T max ), and terminal half-life (t 1/2 ), were comparable between the test and reference products. Adverse events (AEs), mainly hypoglycemia and loose stools events, were reported without relevant differences between the test and reference products. AEs were generally mild and transient. No severe or serious AEs occurred. The new generic drug product of metformin/vildagliptin FDC 850/50 mg demonstrated bioequivalence to the approved product and is therefore expected to provide similar therapeutic effects.