Vildagliptin - Explore the Science & Experts | ideXlab

Scan Science and Technology

Contact Leading Edge Experts & Companies

Vildagliptin

The Experts below are selected from a list of 4629 Experts worldwide ranked by ideXlab platform

Vildagliptin – Free Register to Access Experts & Abstracts

James E Foley – One of the best experts on this subject based on the ideXlab platform.

  • Insights Into GLP-1 and GIP Actions Emerging From Vildagliptin Mechanism Studies in Man
    Frontiers in Endocrinology, 2019
    Co-Authors: James E Foley
    Abstract:

    Vildagliptin blocks glucagon like peptpeptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) inactivation of the meal induced increases in GLP-1 and GIP so that elevated GLP-1 and GIP levels are maintained over 24 hours. The primary insulin secretion effect of Vildagliptin is to improve the impaired sensitivity of the β-cells to glucose in subjects with impaired fastfastingcose (IFG) and impaired glucglucose tolerance (IGT) and in patients with type 2 diabdiabetes mellitus (T2DM); this effect was seen acutely and maintained over at least two years in patients with T2DM. Vildagliptin was also associated with improved β-cell function that is likely secondary to the improved metabolic state. Although there was no evidence of restoration of β-cell mass, the preponderance of the Vildagliptin data does indicate that for at least two years β-cell function was maintained in Vildagliptin treated patients but not in the untreated patients. Vildagliptin suppressed an inappropriate glucagon response to an oral glucose challenge in patients with T2DM, to a mixed meal challenge in patients with T2DM and type 1 diabetes mellitus, and to a mixed meal challenge in subjects with IGT and IFG. The improved glucagon response was maintained for at least 2 years in patients with T2DM and there was no change in the glucagon response in normoglycemic individuals. Vildagliptin lowered glucose levels into the normal range with increasing hypoglycemia but also appeared to protect against insulin therapy induced hypoglycemia. These hypoglycemic benefits appear to be secondary in large part to the improved sensitivity of both the β and α-cell to glucose. In the case of the α-cell, if glucose levels are high, GLP-1 attenuates the glucagon levels and if glucose levels are low, GIP increases glucagon levels. Vildagliptin reduces fatty acid flux from the adipocyte leading to reduced liver fat which in turn leads to increased glucose utilization. The reduced glycosuria and reduced lipo-toxicity associated with Vildagliptin therapy does not lead to weight gain presumably due to increased fat mobilization and oxidation during meals and to reduced fat extraction from the gut.

  • quantification of the contribution of glp 1 to mediating insulinotropic effects of dpp 4 inhibition with Vildagliptin in healthy subjects and patients with type 2 diabetes using exendin 9 39 as a glp 1 receptor antagonist
    Diabetes, 2016
    Co-Authors: Michael A Nauck, Yanling He, Lise Kjems, Jens J Holst, Carolyn F Deacon, Joachim Kind, Lars D Kothe, Matthias Broschag, James E Foley
    Abstract:

    We wanted to quantify the contribution of GLP-1 as a mediator of therapeutic effects of DPP-4 inhibition (Vildagliptin), using the GLP-1 receptor antagonist exendin [9-39] in type 2 diabetic patients and in healthy subjects. 32 patients with type 2 diabetes and 29 age- and weight-matched healthy control subjects were treated, in randomized order, with 100 mg q.d. Vildagliptin or placebo for 10 days. Meal tests were performed (days 9 and 10), without and with a high dose intravenous infusion of exendin [9-39]. The main endpoint was the ratio of integrated insulin secretion rates (total AUC ISR ) and total AUC glucose over 4 h following the meal. Vildagliptin treatment more than doubled responses of intact GLP-1 and GIP and lowered glucose responses without changing AUC ISR /AUC glucose in healthy subjects. Vildagliptin significantly increased this ratio by 10.5 % in type 2-diabetic patients and exendin [9-39] reduced it (both p ISR /AUC glucose ratio achieved with exendin [9-39] was significantly smaller after Vildagliptin than after placebo treatment (p = 0.026) and was equivalent to 47 ± 5% of the increments due to Vildagliptin. Thus, other mediators appear to contribute significantly to the therapeutic effects of DPP-4 inhibition.

  • Vildagliptin-insulin combination improves glycemic control in Asians with type 2 diabetes.
    World Journal of Diabetes, 2013
    Co-Authors: Plamen Kozlovski, James E Foley, Valentina Lukashevich, Q Shao, Wolfgang Kothny
    Abstract:

    AIM: To assess the efficacy and safety of Vildagliptin 50 mg bid as add-on therapy to insulin in Asian patients with type 2 diabdiabetes mellitus (T2DM). METHODS: This was a post hoc analysis of a subgroup of Asian patients from a multicenter, randomized, double-blind, placebo-controlled, parallel-group study in T2DM patients inadequately controlled by stable insulin therapy, with or without metformin. A total of 173 patients were randomized 1:1 to receive treatment with Vildagliptin 50 mg bid (n = 87) or placebo (n = 86) for 24 wk. Changes in HbA1c and fasting plasma glucose (FPG), from baseline to study endpoint, were analyzed using an analysis of covariance model. Change from baseline to endpoint in body weight was summarized by treatment. Safety and tolerability of Vildagliptin was also evaluated. RESULTS: After 24 wk, the difference in adjusted mean change in HbA1c between Vildagliptin and placebo was 0.82% (8.96 mmol/mol; P < 0.001) in Asian subgroup, 0.85% (9.29 mmol/mol; P < 0.001) in patients also receiving metformin, and 0.73% (7.98 mmol/mol; P < 0.001) in patients without metformin, all in favor of Vildagliptin. There was no significant difference in the change in FPG between treatments. Weight was stable in both treatment groups (+0.3 kg and -0.2 kg, for Vildagliptin and placebo, respectively). Overall, Vildagliptin was safe and well tolerated with similarly low incidences of hypoglycemia (8.0% vs 8.1%) and no severe hypoglycemic events were experienced in either group. CONCLUSION: In Asian patients inadequately controlled with insulin (with or without concomitant metformin), insulinVildagliptin combination treatment significantly reduced HbA1c compared with placebo, without an increase in risk of hypoglycemia or weight gain.

Anja Schweizer – One of the best experts on this subject based on the ideXlab platform.

  • cardiovascular and heart failure safety profile of Vildagliptin a meta analysis of 17 000 patients
    Diabetes Obesity and Metabolism, 2015
    Co-Authors: G Mcinnes, Valentina Lukashevich, S Del Prato, Anja Schweizer, Q Shao, Marc Evans, Michael Stumvoll, Wolfgang Kothny
    Abstract:

    Aims To report the cardiovascular (CV) safety profile and heart failure (HF) risk of Vildagliptin from a large pool of studies, including trials in high-risk patients with type 2 diabdiabetes mellitus (T2DM), such as those with congestive HF and/or moderate/severe renal impairment. Methods We conducted a retrospective meta-analysis of prospectively adjudicated CV events. Patient-level data were pooled from 40 double-blind, randomized controlled phase III and IV Vildagliptin studies. The primary endpoint was occurrence of major adverse CV events (MACEs; myocardial infainfarction, stroke and CV death). Assessments of the individual MACE components and HF events (requiring hospitalization or new onset) were secondary endpoints. The risk ratio (RR) of Vildagliptin (50 mg once- and twice-daily combined) versus comparators (placebo and all non-Vildagliptin treatments) was calculated using the Mantel–Haenszel (M–H) method. Results Of the 17 446 patients, 9599 received Vildagliptin (9251.4 subject-years of exposure) and 7847 received comparators (7317.0 subject-years of exposure). The mean age of the patients was 57 years, body mass index 30.5 kg/m2 (nearly 50% obese), glycated haemoglobin concentration 8.1% and T2DM duration 5.5 years. A MACE occurred in 83 (0.86%) Vildagliptin-treated patients and 85 (1.20%) comparator-treated patients, with an M-H RR of 0.82 [95% confidence interval (CI) 0.61–1.11]. Similar RRs were observed for the individual events. Confirmed HF events were reported in 41 (0.43%) Vildagliptin-treated patients and 32 (0.45%) comparator-treated patients, with an M–H RR 1.08 (95% CI 0.68–1.70). Conclusions This large meta-analysis indicates that Vildagliptin is not associated with an increased risk of adjudicated MACEs relative to comparators. Moreover, this analysis did not find a significant increased risk of HF in Vildagliptin-treated patients.

  • Cardiovascular and heart failure safety profile of Vildagliptin: a meta‐analysis of 17 000 patients
    Diabetes Obesity and Metabolism, 2015
    Co-Authors: G Mcinnes, Valentina Lukashevich, S Del Prato, Anja Schweizer, Q Shao, Marc Evans, Michael Stumvoll, Wolfgang Kothny
    Abstract:

    Aims To report the cardiovascular (CV) safety profile and heart failure (HF) risk of Vildagliptin from a large pool of studies, including trials in high-risk patients with type 2 diabdiabetes mellitus (T2DM), such as those with congestive HF and/or moderate/severe renal impairment. Methods We conducted a retrospective meta-analysis of prospectively adjudicated CV events. Patient-level data were pooled from 40 double-blind, randomized controlled phase III and IV Vildagliptin studies. The primary endpoint was occurrence of major adverse CV events (MACEs; myocardial infainfarction, stroke and CV death). Assessments of the individual MACE components and HF events (requiring hospitalization or new onset) were secondary endpoints. The risk ratio (RR) of Vildagliptin (50 mg once- and twice-daily combined) versus comparators (placebo and all non-Vildagliptin treatments) was calculated using the Mantel–Haenszel (M–H) method. Results Of the 17 446 patients, 9599 received Vildagliptin (9251.4 subject-years of exposure) and 7847 received comparators (7317.0 subject-years of exposure). The mean age of the patients was 57 years, body mass index 30.5 kg/m2 (nearly 50% obese), glycated haemoglobin concentration 8.1% and T2DM duration 5.5 years. A MACE occurred in 83 (0.86%) Vildagliptin-treated patients and 85 (1.20%) comparator-treated patients, with an M-H RR of 0.82 [95% confidence interval (CI) 0.61–1.11]. Similar RRs were observed for the individual events. Confirmed HF events were reported in 41 (0.43%) Vildagliptin-treated patients and 32 (0.45%) comparator-treated patients, with an M–H RR 1.08 (95% CI 0.68–1.70). Conclusions This large meta-analysis indicates that Vildagliptin is not associated with an increased risk of adjudicated MACEs relative to comparators. Moreover, this analysis did not find a significant increased risk of HF in Vildagliptin-treated patients.

  • clinical evidence and mechanistic basis for Vildagliptin s effect in combination with insulin
    Vascular Health and Risk Management, 2013
    Co-Authors: Anja Schweizer, James E Foley, Wolfgang Kothny, Bo Ahren
    Abstract:

    Due to the progressive nature of type 2 diabetes, many patients need insulin as add-on to oral antidiabetic drugs (OADs) in order to maintain adequate glycemic control. Insulin therapy primarily targets elevated fasting glycemia but is less effective to reduce postprandial hyperglycemia. In addition, the risk of hypoglycemia limits its effectiveness and there is a concern of weight gain. These drawbacks may be overcome by combining insulin with incretin-based therapies as these increase glucose sensitivity of both the α- and β-cells, resulting in improved postprandial glycemia without the hypoglycemia and weight gain associated with increasing the dose of insulin. The dipeptidyl peptidase-IV (DPP-4) inhibitor Vildagliptin has also been shown to protect from hypoglycemia by enhancing glucagon counterregulation. The effectiveness of combining Vildagliptin with insulin was demonstrated in three different studies in which Vildagliptin decreased A1C levels when added to insulin therapy without increasing hypoglycemia. This was established with and without concomitant metformin therapy. Furthermore, the effectiveness of Vildagliptin appears to be greater when insulin is used as a basal regimen as opposed to being used to reduce postprandial hyperglycemia, since improvement in insulin secretion likely plays a minor role when relatively high doses of insulin are administered before meals. This article reviews the clinical experience with the combination of Vildagliptin and insulin and discusses the mechanistic basis for the beneficial effects of the combination. The data support the use of Vildagliptin in combination with insulin in general and, in line with emerging clinical practice, suggest that treating patients with Vildagliptin, metformin, and basal insulin could be an attractive therapeutic option.

S Dejager – One of the best experts on this subject based on the ideXlab platform.

  • mechanisms of action of the dipeptidyl peptidase 4 inhibitor Vildagliptin in humans
    Diabetes Obesity and Metabolism, 2011
    Co-Authors: Bo Ahren, Anja Schweizer, S Dejager, Edwin Bernard Villhauer, B E Dunning, James E Foley
    Abstract:

    Inhibition of dipeptidyl peptidase-4 (DPP-4) by Vildagliptin prevents degradation of glucagon-like peptpeptidea> (GLP-1) and reduces glycemia in type 2 diabetes, with low risk for hypoglycemia and no weight gain. Vildagliptin binds covalently to the catalytic site of DPP-4, eliciting prolonged enzyme inhibition. This raises intact GLP-1 levels, both after meal ingestion and in the fasting state. Vildagliptin has been shown to stimulate insulin secretion and to inhibit glucagon secretion in a glucose-dependent manner. At hypoglycemic levels, the counterregulatory glucagon response is enhanced relative to baseline by Vildagliptin. Vildagliptin also inhibits hepatic glucose production, mainly through changes in islet hormone secretion, and improves insulin sensitivity, as determined with a variety of methods. These effects underlie the improved glycemia with low risk for hypoglycemia. Vildagliptin also suppresses postprandial triglyceride-rich lipoprotein levels after ingestion of a fat-rich meal and reduces fasting lipolysis, suggesting inhibition of fat absorption and reduced triglyceride stores in non-fat tissues. The large body of knowledge on Vildagliptin regarding enzyme binding, incretin and islet hormone secretion and glucose and lipid metabolism is summarized, with discussion of the integrated mechanisms and comparison with other DPP-4 inhibitors and GLP-1 receptor activators, where appropriate.

  • assessing the general safety and tolerability of Vildagliptin value of pooled analyses from a large safety database versus evaluation of individual studies
    Vascular Health and Risk Management, 2011
    Co-Authors: Anja Schweizer, James E Foley, S Dejager, Wolfgang Kothny
    Abstract:

    AIM: Analyzing safety aspects of a drug from individual studies can lead to difficult-to-interpret results. The aim of this paper is therefore to assess the general safety and tolerability, including incidences of the most common adverse events (AEs), of Vildagliptin based on a large pooled database of Phase II and III clinical trials. METHODS: Safety data were pooled from 38 studies of ≥ 12 to ≥ 104 weeks’ duration. AE profiles of Vildagliptin (50 mg bid; N = 6116) were evaluated relative to a pool of comparators (placebo and active comparators; N = 6210). Absolute incidence rates were calculated for all AEs, serious AEs (SAEs), discontinuations due to AEs, and deaths. RESULTS: Overall AEs, SAEs, discontinuations due to AEs, and deaths were all reported with a similar frequency in patients receiving Vildagliptin (69.1%, 8.9%, 5.7%, and 0.4%, respectively) and patients receiving comparators (69.0%, 9.0%, 6.4%, and 0.4%, respectively), whereas drug-related AEs were seen with a lower frequency in Vildagliptin-treated patients (15.7% vs 21.7% with comparators). The incidences of the most commonly reported specific AEs were also similar between Vildagliptin and comparators, except for increased incidences of hypoglycemia, tremor, and hyperhidrosis in the comparator group related to the use of sulfonylureas. CONCLUSIONS: The present pooled analysis shows that Vildagliptin was overall well tolerated in clinical trials of up to >2 years in duration. The data further emphasize the value of a pooled analysis from a large safety database versus assessing safety and tolerability from individual studies.

  • clinical experience with Vildagliptin in the management of type 2 diabetes in a patient population 75 years a pooled analysis from a database of clinical trials
    Diabetes Obesity and Metabolism, 2011
    Co-Authors: Anja Schweizer, James E Foley, S Dejager, Q Shao, Wolfgang Kothny
    Abstract:

    AIM: To report the experience with Vildagliptin in a patient population with type 2 diabdiabetes mellitus (T2DM) ≥75 years. METHODS: Efficacy data from seven monotherapy and three add-on therapy to metformin studies, respectively, of ≥24 weeks duration were pooled; effects of 24 weeks of treatment with Vildagliptin (50 mg bid) in patients ≥75 years were assessed in these two pooled datasets. Safety data were pooled from 38 studies of ≥12 to ≥104 weeks duration; adverse events (AEs) profiles of Vildagliptin (50 mg bid) were evaluated relative to a pool of comparators; 301 patients ≥75 years were analysed. Data in patients <75 years are provided as a reference. RESULTS: Mean age of the elderly population was 77 years. Changes in haemoglobin A1c (HbA1c) with Vildagliptin in the patient group ≥75 years were -0.9% from a baseline of 8.3% in monotherapy (p < 0.0001) and -1.1% from a baseline of 8.5% in add-on therapy to metformin (p = 0.0004), and these reductions were similar to those seen in the younger patients. The corresponding weight changes in the elderly patients were -0.9 kg (p = 0.0277) and -0.2 kg [not significant (NS)], respectively, and no confirmed hypoglycaemic events, including no severe events, were reported. AEs, drug-related AEs, serious adverse events (SAEs) and deaths were reported with a lower frequency in older patients receiving Vildagliptin than comparators [133.9 vs. 200.6, 14.5 vs. 21.8, 8.8 vs. 16.5 and 0.0 vs. 1.7 events per 100 subject year exposure (SYE), respectively], and the incidence of discontinuations due to AEs was similar in the two groups (7.2 vs. 7.5 events per 100 SYE, respectively). The safety profile of Vildagliptin was overall similar in younger and older patients. CONCLUSIONS: Vildagliptin was effective and well-tolerated in type 2 diabetic patients ≥75 years (mean age 77 years).

Wolfgang Kothny – One of the best experts on this subject based on the ideXlab platform.

  • effects of Vildagliptin on ventricular function in patients with type 2 diabetes mellitus and heart failure a randomized placebo controlled trial
    Jacc-Heart Failure, 2018
    Co-Authors: Valentina Lukashevich, Wolfgang Kothny, Geremia B Bolli, Plamen Kozlovski, John J V Mcmurray, Piotr Ponikowski, James D Lewsey, Henry Krum
    Abstract:

    Abstract Objectives This study sought to examine the safety of the dipeptidyl peptpeptidasenhiinhibitor, Vildagliptin, in patients with heart failure and reduced ejection fraction. Background Many patients with type 2 diabdiabetes mellitus have heart failure and it is important to know about the safety of new treatments for diabetes in these individuals. Methods Patients 18 to 85 years of age with type 2 diabetes and heart failure (New York Heart Association functional class I to III and left ventricular ejection fraction [LVEF]  Results A total of 254 patients were randomly assigned to Vildagliptin (n = 128) or placebo (n = 126). Baseline LVEF was 30.6 ± 6.8% in the Vildagliptin group and 29.6 ± 7.7% in the placebo group. The adjusted mean change in LVEF was 4.95 ± 1.25% in Vildagliptin treated patients and 4.33 ± 1.23% in placebo treated patients, a difference of 0.62 (95% confidence interval [CI]: −2.21 to 3.44; p = 0.667). This difference met the predefined noninferiority margin of −3.5%. Left ventricular end-diastolic and end-systolic volumes increased more in the Vildagliptin group by 17.1 ml (95% CI: 4.6 to 29.5 ml; p = 0.007) and 9.4 ml (95% CI: −0.49 to 19.4 ml; p = 0.062), respectively. Decrease in hemoglobin A 1c  from baseline to 16 weeks, the main secondary endpoint, was greater in the Vildagliptin group: −0.62% (95% CI: −0.93 to −0.30%; p  Conclusions Compared with placebo, Vildagliptin had no major effect on LVEF but did lead to an increase in left ventricular volumes, the cause and clinical significance of which is unknown. More evidence is needed regarding the safety of dipeptidyl peptidase-4 inhibitors in patients with heart failure and left ventricular systolic dysfunction. (Effect of Vildagliptin on Left Ventricular Function in Patients With Type 2 Diabetes and Congestive Heart Failure; NCT00894868)

  • cardiovascular and heart failure safety profile of Vildagliptin a meta analysis of 17 000 patients
    Diabetes Obesity and Metabolism, 2015
    Co-Authors: G Mcinnes, Valentina Lukashevich, S Del Prato, Anja Schweizer, Q Shao, Marc Evans, Michael Stumvoll, Wolfgang Kothny
    Abstract:

    Aims To report the cardiovascular (CV) safety profile and heart failure (HF) risk of Vildagliptin from a large pool of studies, including trials in high-risk patients with type 2 diabetes mellitus (T2DM), such as those with congestive HF and/or moderate/severe renal impairment. Methods We conducted a retrospective meta-analysis of prospectively adjudicated CV events. Patient-level data were pooled from 40 double-blind, randomized controlled phase III and IV Vildagliptin studies. The primary endpoint was occurrence of major adverse CV events (MACEs; myocardial infarction, stroke and CV death). Assessments of the individual MACE components and HF events (requiring hospitalization or new onset) were secondary endpoints. The risk ratio (RR) of Vildagliptin (50 mg once- and twice-daily combined) versus comparators (placebo and all non-Vildagliptin treatments) was calculated using the Mantel–Haenszel (M–H) method. Results Of the 17 446 patients, 9599 received Vildagliptin (9251.4 subject-years of exposure) and 7847 received comparators (7317.0 subject-years of exposure). The mean age of the patients was 57 years, body mass index 30.5 kg/m2 (nearly 50% obese), glycated haemoglobin concentration 8.1% and T2DM duration 5.5 years. A MACE occurred in 83 (0.86%) Vildagliptin-treated patients and 85 (1.20%) comparator-treated patients, with an M-H RR of 0.82 [95% confidence interval (CI) 0.61–1.11]. Similar RRs were observed for the individual events. Confirmed HF events were reported in 41 (0.43%) Vildagliptin-treated patients and 32 (0.45%) comparator-treated patients, with an M–H RR 1.08 (95% CI 0.68–1.70). Conclusions This large meta-analysis indicates that Vildagliptin is not associated with an increased risk of adjudicated MACEs relative to comparators. Moreover, this analysis did not find a significant increased risk of HF in Vildagliptin-treated patients.

  • Cardiovascular and heart failure safety profile of Vildagliptin: a meta‐analysis of 17 000 patients
    Diabetes Obesity and Metabolism, 2015
    Co-Authors: G Mcinnes, Valentina Lukashevich, S Del Prato, Anja Schweizer, Q Shao, Marc Evans, Michael Stumvoll, Wolfgang Kothny
    Abstract:

    Aims To report the cardiovascular (CV) safety profile and heart failure (HF) risk of Vildagliptin from a large pool of studies, including trials in high-risk patients with type 2 diabetes mellitus (T2DM), such as those with congestive HF and/or moderate/severe renal impairment. Methods We conducted a retrospective meta-analysis of prospectively adjudicated CV events. Patient-level data were pooled from 40 double-blind, randomized controlled phase III and IV Vildagliptin studies. The primary endpoint was occurrence of major adverse CV events (MACEs; myocardial infarction, stroke and CV death). Assessments of the individual MACE components and HF events (requiring hospitalization or new onset) were secondary endpoints. The risk ratio (RR) of Vildagliptin (50 mg once- and twice-daily combined) versus comparators (placebo and all non-Vildagliptin treatments) was calculated using the Mantel–Haenszel (M–H) method. Results Of the 17 446 patients, 9599 received Vildagliptin (9251.4 subject-years of exposure) and 7847 received comparators (7317.0 subject-years of exposure). The mean age of the patients was 57 years, body mass index 30.5 kg/m2 (nearly 50% obese), glycated haemoglobin concentration 8.1% and T2DM duration 5.5 years. A MACE occurred in 83 (0.86%) Vildagliptin-treated patients and 85 (1.20%) comparator-treated patients, with an M-H RR of 0.82 [95% confidence interval (CI) 0.61–1.11]. Similar RRs were observed for the individual events. Confirmed HF events were reported in 41 (0.43%) Vildagliptin-treated patients and 32 (0.45%) comparator-treated patients, with an M–H RR 1.08 (95% CI 0.68–1.70). Conclusions This large meta-analysis indicates that Vildagliptin is not associated with an increased risk of adjudicated MACEs relative to comparators. Moreover, this analysis did not find a significant increased risk of HF in Vildagliptin-treated patients.

Yanling He – One of the best experts on this subject based on the ideXlab platform.

  • Bioequivalence and food effect assessment for Vildagliptin/metformin fixed-dose combination tablets relative to free combination of Vildagliptin and metformin in Japanese healthy subjects.
    International journal of clinical pharmacology and therapeutics, 2016
    Co-Authors: Sachiko Mita, Yanling He, Kenneth Kulmatycki, Shripad D. Chitnis, Atish Salunke, Wei Zhou, Hikoe Suzuki
    Abstract:

    Objective To assess the bioequivalence of Vildagliptin/metformin fixeddose combination (FDC) tablets (50/250 mg and 50/500 mg) to free combinations of Vildagliptin and metformin and the effect of food on the pharmacokinetics (PK) of Vildagliptin and metformin following administration of 50/500 mg FDC tablets. Methods Two openlabel, randomized, single-center, singledose, 2-period crossover studies were conducted in Japanese healthy male volunteers. Participants were administered Vildagliptin/ metformin FDC tablets (study I: 50/250 mg, study II: 50/500 mg) or their free combinations under fasted condition. Food effect (standard Japanese breakfast: fat, 20 – 30% with ~ 600 kcal in total) was assessed during an additional period in study II (50/500 mg). PK parameters (AUC, C(max), t(max), t(1/2)) were calculated for Vildagliptin and metformin. Results In both studies, Vildagliptin/metformin FDC tablets were bioequivalent to their respective free combinations. Administration of FDC tablets after meals had no effect on Vildagliptin PK parameters. The rate of absorption of metformin decreased when administered under fed condition, as reflected by a prolonged t(max) (3 hours in fasted state vs. 4 hours in fed state) and decrease in C(max) by 26%, however, the extent of absorption (AUC(last)) was similar to that in the fasted state. Conclusions Vildagliptin/metformin FDC tablets were bioequivalent to their free combinations. Food decreased the C(max) of metformin by 26%, while AUC(last) was unchanged, consistent with previous reports. No food effect was observed on the C(max) or AUC(last) of Vildagliptin. Thus, food had no clinically relevant effects on the PK of metformin or Vildagliptin.

  • quantification of the contribution of glp 1 to mediating insulinotropic effects of dpp 4 inhibition with Vildagliptin in healthy subjects and patients with type 2 diabetes using exendin 9 39 as a glp 1 receptor antagonist
    Diabetes, 2016
    Co-Authors: Michael A Nauck, Yanling He, Lise Kjems, Jens J Holst, Carolyn F Deacon, Joachim Kind, Lars D Kothe, Matthias Broschag, James E Foley
    Abstract:

    We wanted to quantify the contribution of GLP-1 as a mediator of therapeutic effects of DPP-4 inhibition (Vildagliptin), using the GLP-1 receptor antagonist exendin [9-39] in type 2 diabetic patients and in healthy subjects. 32 patients with type 2 diabetes and 29 age- and weight-matched healthy control subjects were treated, in randomized order, with 100 mg q.d. Vildagliptin or placebo for 10 days. Meal tests were performed (days 9 and 10), without and with a high dose intravenous infusion of exendin [9-39]. The main endpoint was the ratio of integrated insulin secretion rates (total AUC ISR ) and total AUC glucose over 4 h following the meal. Vildagliptin treatment more than doubled responses of intact GLP-1 and GIP and lowered glucose responses without changing AUC ISR /AUC glucose in healthy subjects. Vildagliptin significantly increased this ratio by 10.5 % in type 2-diabetic patients and exendin [9-39] reduced it (both p ISR /AUC glucose ratio achieved with exendin [9-39] was significantly smaller after Vildagliptin than after placebo treatment (p = 0.026) and was equivalent to 47 ± 5% of the increments due to Vildagliptin. Thus, other mediators appear to contribute significantly to the therapeutic effects of DPP-4 inhibition.

  • Pharmacokinetics of Vildagliptin in patients with varying degrees of renal impairment.
    International journal of clinical pharmacology and therapeutics, 2013
    Co-Authors: Yanling He, Kenneth Kulmatycki, Monica Ligueros-saylan, Wei Zhou, Yiming Zhang, Christine Reynolds, Ann Taylor
    Abstract:

    OBJECTIVE: The kidney plays a key role in both the metabolism and excretion of Vildagliptin. This study was designed to investigate the effects of varying degrees of renal impairment (RI) on the pharmacokinetics of Vildagliptin. METHODS: A total of 96 subjects were enrolled, and each subject received Vildagliptin 50 mg dosed orally once daily for 14 days. Vildagliptin and metabolite concentrations in plasma and urine were measured on Days 1 and 14. RESULTS: Compared to age-, gender-, BMI-matched subjects with normal renal function, the mean AUC of Vildagliptin after 14 days in patients with mild, moderate, and severe RI increased by 40%, 71%, and 100%, respectively, and the Cmax of Vildagliptin showed similar and minimal increases of 37%, 32% and 36%, respectively. CONCLUSIONS: These pharmacokinetics results suggest that 50 mg once daily is an appropriate dose and recommended for patients with moderate and severe renal impairment.