ArticleJournal of pharmacokinetics and pharmacodynamics2013
A semi-mechanistic model of the relationship between average glucose and HbA1c in healthy and diabetic subjects.
Article in Journal of pharmacokinetics and pharmacodynamics, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers, 1 of them a synthesis that pooled it.
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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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
19 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Efficacy of DPP-4 inhibitors, GLP-1 analogues, and SGLT2 inhibitors as add-ons to metformin monotherapy in T2DM patients: a model-based meta-analysis.British journal of clinical pharmacology · 2019Pooled it
- Danuglipron (PF-06882961) in type 2 diabetes: a randomized, placebo-controlled, multiple ascending-dose phase 1 trial.Nature medicine · 2021Trial
- Weight-HbA1c-insulin-glucose model for describing disease progression of type 2 diabetes.CPT: pharmacometrics & systems pharmacology · 2016Trial
- Evaluation of the long-term durability and glycemic control of fasting plasma glucose and glycosylated hemoglobin for pioglitazone in Japanese patients with type 2 diabetes.Diabetes technology & therapeutics · 2015Trial
- A Review of Semi-Mechanistic HbA1c Models in People with Type 2 Diabetes: Strengths, Limitations, and Applications.Journal of clinical pharmacology · 2026Review
- From In Vitro Efficacy to Long-Term HbA1c Response for GLP-1R/GlucagonR Agonism Using the 4GI-HbA1c Systems Model.CPT: pharmacometrics & systems pharmacology · 2025Article
- Evaluation of Four Semi-Mechanistic Models for Predicting Glycemic Control With a Glucagon Receptor Antagonist in People With Type 2 Diabetes.CPT: pharmacometrics & systems pharmacology · 2025Article
- A mechanistic modeling platform of SGLT2 inhibition: Implications for type 1 diabetes.CPT: pharmacometrics & systems pharmacology · 2023Article
- Optimization of trial duration to predict long-term HbA1c change with therapy: A pharmacometrics simulation-based evaluation.CPT: pharmacometrics & systems pharmacology · 2022Article
- 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
- Prior information for population pharmacokinetic and pharmacokinetic/pharmacodynamic analysis: overview and guidance with a focus on the NONMEM PRIOR subroutine.Journal of pharmacokinetics and pharmacodynamics · 2020Review
- Urinary glucose excretion after dapagliflozin treatment: An exposure-response modelling comparison between Japanese and non-Japanese patients diagnosed with type 1 diabetes mellitus.Diabetes, obesity & metabolism · 2019Article
- Comparison of Power, Prognosis, and Extrapolation Properties of Four Population Pharmacodynamic Models of HbA1c for Type 2 Diabetes.CPT: pharmacometrics & systems pharmacology · 2018Article
- Glycated Hemoglobin, Plasma Glucose, and Erythrocyte Aging.Journal of diabetes science and technology · 2016Article
- Mechanistic modeling of hemoglobin glycation and red blood cell kinetics enables personalized diabetes monitoring.Science translational medicine · 2016Article
- A Comprehensive Review of Novel Drug-Disease Models in Diabetes Drug Development.Clinical pharmacokinetics · 2016Review
- Validation of a hemoglobin A1c model in patients with type 1 and type 2 diabetes and its use to go beyond the averaged relationship of hemoglobin A1c and mean glucose level.Journal of translational medicine · 2014Article
- Methods for Predicting Diabetes Phase III Efficacy Outcome From Early Data: Superior Performance Obtained Using Longitudinal Approaches.CPT: pharmacometrics & systems pharmacology · 2014Article
- Pharmacometrics Approaches and its Applications in Diabetes: An Overview.Journal of pharmacy & bioallied sciencesReview
Corrections and comments
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Authors and funding
3 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
HbA1c is the most commonly used biomarker for the adequacy of glycemic management in diabetic patients and a surrogate endpoint for anti-diabetic drug approval. In spite of an empirical description for the relationship between average glucose (AG) and HbA1c concentrations, obtained from the A1c-derived average glucose (ADAG) study by Nathan et al., a model for the non-steady-state relationship is still lacking. Using data from the ADAG study, we here develop such models that utilize literature information on (patho)physiological processes and assay characteristics. The model incorporates the red blood cell (RBC) aging description, and uses prior values of the glycosylation rate constant (KG), mean RBC life-span (LS) and mean RBC precursor LS obtained from the literature. Different hypothesis were tested to explain the observed non-proportional relationship between AG and HbA1c. Both an inverse dependence of LS on AG and a non-specificity of the National Glycohemoglobin Standardization Program assay used could well describe the data. Both explanations have mechanistic support and could be incorporated, alone or in combination, in models allowing prediction of the time-course of HbA1c changes associated with changes in AG from, for example dietary or therapeutic interventions, and vice versa, to infer changes in AG from observed changes in HbA1c. The selection between the alternative mechanistic models require gathering of new information.
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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.