Trial reportBritish journal of clinical pharmacology2012
Mechanism-based population modelling of the effects of vildagliptin on GLP-1, glucose and insulin in patients with type 2 diabetes.
Trial report in British journal of clinical pharmacology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
12 citing papers in PubMed, 23 citations in OpenAlex.
- Assessment of glycemic response to an oral glucokinase activator in a proof of concept study: application of a semi-mechanistic, integrated glucose-insulin-glucagon model.Journal of pharmacokinetics and pharmacodynamics · 2013Trial
- Study reanalysis using a mechanism-based pharmacokinetic/pharmacodynamic model of pramlintide in subjects with type 1 diabetes.The AAPS journal · 2013Trial
- Mechanism-based population pharmacokinetic modelling in diabetes: vildagliptin as a tight binding inhibitor and substrate of dipeptidyl peptidase IV.British journal of clinical pharmacology · 2012Trial
- A physiologically-based quantitative systems pharmacology model for mechanistic understanding of the response to alogliptin and its application in patients with renal impairment.Journal of pharmacokinetics and pharmacodynamics · 2025Article
- A novel integrated QSP model of in vivo human glucose regulation to support the development of a glucagon/GLP-1 dual agonist.CPT: pharmacometrics & systems pharmacology · 2022Article
- Evolving data analysis of an Oral Lipid Tolerance Test toward the standard for the Oral Glucose Tolerance Test: Cross species modeling effects of AZD7687 on plasma triacylglycerol.Pharmacology research & perspectives · 2019Article
- In vitro and in silico analysis of the effects of DBritish journal of pharmacology · 2018Article
- A Comprehensive Review of Novel Drug-Disease Models in Diabetes Drug Development.Clinical pharmacokinetics · 2016Review
- Population Pharmacokinetic/Pharmacodynamic Modelling of Dipeptidyl Peptidase IV Inhibitors.Clinical pharmacokinetics · 2015Article
- The Effects of a GLP-1 Analog on Glucose Homeostasis in Type 2 Diabetes Mellitus Quantified by an Integrated Glucose Insulin Model.CPT: pharmacometrics & systems pharmacology · 2015 · on this mapArticle
- Evaluating systems pharmacology models is different from evaluating standard pharmacokinetic-pharmacodynamic models.CPT: pharmacometrics & systems pharmacology · 2014Article
- Mechanism-based model of parasite growth and dihydroartemisinin pharmacodynamics in murine malaria.Antimicrobial agents and chemotherapy · 2013Article
Corrections and comments
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Authors and funding
3 authors at 3 institutions in 3 countries.
Funding
Abstract
aimTo build a mechanism-based population pharmacodynamic model to describe and predict the time course of active GLP-1, glucose and insulin in type 2 diabetic patients after treatment with various doses of vildagliptin.
methodsVildagliptin concentrations, DPP-4 activity, active GLP-1, glucose and insulin concentrations from 13 type 2 diabetic patients after oral vildagliptin doses of 10, 25 or 100 mg and placebo twice daily for 28 days were co-modelled. The population PK/PD model was developed utilizing the MC-PEM algorithm in parallelized S-ADAPT version 1.56.
resultsIn the PD model, active GLP-1 production was stimulated by gastrointestinal intake of nutrients. Active GLP-1 was primarily metabolized by DPP-4 and an additional non-saturable pathway. Increased plasma glucose stimulated secretion of insulin which stimulated utilization of glucose. Active GLP-1 stimulated both glucose-dependent insulin secretion and insulin-dependent glucose utilization. Complete inhibition of DPP-4 resulted in an approximately 2.5-fold increase of active GLP-1 half-life.
conclusionsThe effects of vildagliptin in patients with type 2 diabetes on several PD endpoints were successfully described by the proposed model. The mechanisms of vildagliptin on glycaemic control could be evaluated from a variety of aspects such as effects of DPP-4 on GLP-1, effects of GLP-1 on insulin secretion and effects on hepatic and peripheral insulin sensitivity. The present model can be used to predict the effects of other dosage regimens of vildagliptin on DPP-4 inhibition, active GLP-1, glucose and insulin concentrations, or can be modified and applied to other incretin-related anti-diabetes therapies.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.