Evidence mapPaperPMID 41489799Full record

Trial reportClinical pharmacokinetics2026

Population Pharmacokinetic and Pharmacodynamic Modeling to Support Molar Dose Ratio Determination of Long-Acting Insulin Analogs.

Dan Tang, Xuehu Gao, Min Zhu, Chang Shu, Yanli Dong, Xiaoling Yu, Hong Chen, Xiaojuan Li, Xiaoli Zhang, Daren Cai and 1 more

Abstract readClinical Trial, Phase IIClinical Trial, Phase IRandomized Controlled Trial
PubMed Publisher
In one paragraph

Trial report in Clinical pharmacokinetics, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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0citing papers in PubMed
field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

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.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

11 authors.

Dan TangClinical Pharmacology Department, Jiangsu Hengrui Pharmaceuticals Co., Ltd, Shanghai, China.
Xuehu GaoClinical Pharmacology Department, Jiangsu Hengrui Pharmaceuticals Co., Ltd, Shanghai, China.
Min ZhuClinical Pharmacology Department, Jiangsu Hengrui Pharmaceuticals Co., Ltd, Shanghai, China.
Chang ShuClinical Pharmacology Department, Jiangsu Hengrui Pharmaceuticals Co., Ltd, Shanghai, China.
Yanli DongClinical Pharmacology Department, Jiangsu Hengrui Pharmaceuticals Co., Ltd, Shanghai, China.
Xiaoling YuMetabolic Diseases, Clinical Development, Jiangsu Hengrui Pharmaceuticals Co., Ltd, Shanghai, China.
Hong ChenMetabolic Diseases, Clinical Development, Jiangsu Hengrui Pharmaceuticals Co., Ltd, Shanghai, China.
Xiaojuan LiDepartment of Biometrics, Jiangsu Hengrui Pharmaceuticals Co., Ltd, Shanghai, China.
Xiaoli ZhangDepartment of Biometrics, Jiangsu Hengrui Pharmaceuticals Co., Ltd, Shanghai, China.
Daren CaiDepartment of Biometrics, Jiangsu Hengrui Pharmaceuticals Co., Ltd, Shanghai, China.
Sheng FengClinical Pharmacology Department, Jiangsu Hengrui Pharmaceuticals Co., Ltd, Shanghai, China. CP.Publication@hengrui.com.ORCID 0009-0009-0439-635X

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

BACKGROUND AND

objectiveINS068 is a new soluble, long-acting insulin analog intended to cover basal insulin requirements in patients with type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM). The purpose of this study was to determine the molar dose ratio of INS068 to insulin degludec (IDeg) by comparing the clinical pharmacokinetic (PK) and pharmacodynamic (PD) profiles of INS068 and IDeg. The PD endpoints include glucose infusion rate (GIR) and glycated hemoglobin (HbA1c).

methodPopulation pharmacokinetic and pharmacodynamic (PopPK/PD) analysis was performed to characterize INS068 and IDeg PK and PD profiles. Data from 307 subjects across three Phase I studies and one Phase II study were used to establish the population pharmacokinetic (PopPK) model, of which two euglycemic clamp (Phase I) studies were used to establish PopPK-GIR model, and one Phase II study was used to establish PopPK-HbA1c model. Nonlinear mixed-effects modeling was used to investigate the PK and PD relationships of INS068 and IDeg. Model-based simulations were performed to determine the molar dose ratio of INS068 to IDeg.

resultsThe PopPK model of INS068 and IDeg was described by a one-compartment model with linear absorption with a lag time and elimination. Significant covariate effects of body weight, population, and treatment (INS068 vs IDeg) were identified for PK parameters of INS068 and IDeg. However, except for body weight and T2DM patients, the other significant covariates (treatment and T1DM patients) had no clinically relevant effects on PK exposures. The relationship between GIR and insulin concentrations in effect compartment was described by a direct response model with sigmoidal E

conclusionThis analysis supported molar dose ratio of INS068 to IDeg as 1. INS068 had similar potency compared to IDeg, with one unit of INS068 composed of 6 nmol of active ingredient (1 U = 6 nmol).

Indexed as

Hypoglycemic AgentsInsulin, Long-ActingModels, BiologicalAdolescentAdultAgedBlood GlucoseDiabetes Mellitus, Type 1Diabetes Mellitus, Type 2Dose-Response Relationship, DrugFemaleGlucose Clamp TechniqueGlycated HemoglobinHumansMaleMiddle AgedBlood GlucoseGlycated HemoglobinHypoglycemic Agentsinsulin degludecInsulin, Long-Acting

Identifiers

PMID41489799

What Socratic holds

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Registered trials

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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 Socratic graph.