Population pharmacokinetics of efpeglenatide in individuals with obesity and with type 2 diabetes.

Choi S, Seo J, Park S, Kim NY, Kim H, Lim HS

Frontiers in pharmacology1 Dec 2025

PMID41403449PMCIDPMC12702981DOI10.3389/fphar.2025.1715585PepBankPUB-41403449

Summary

BackgroundEfpeglenatide (HM11260C) is a long-acting GLP-1 receptor agonist under development for obesity. A population pharmacokinetic (PK) analysis was conducted to characterize its PK properties and evaluate covariate effects to support clinical dosing strategies.MethodsPooled PK data from six clinical studies in participants with type 2 diabetes or obesity were analyzed using nonlinear mixed-effects modeling (NONMEM). Covariate effects, model diagnostics, and simulations were used to assess exposure and dosing strategies.ResultsA two-compartment model with dual absorption pathways adequately described the data. Body weight and disease status influenced absorption and clearance; however, predicted exposure differences across weight percentiles and demographic subgroups were modest and within conventional bioequivalence limits. Simulations suggested approximately dose-proportional increases across the evaluated dose range with once-weekly administration and supported the feasibility of stepwise dose-escalation.ConclusionEfpeglenatide PK was well characterized across type 2 diabetes and obesity populations. Although some covariates affected PK parameters, their impact on exposure was not clinically meaningful. These results support a uniform dosing strategy without routine dose adjustment and provide quantitative evidence for stepwise dose escalation in ongoing clinical development for obesity.

CC BYText from Europe PMC. Highlighted sentences are the source of results.

Results from this study5

2 results from studies that gave the peptide. 2 results from people.

01HumanObservational studyPharmacokinetics
In participants with diabetes or obesity, a two-compartment model with dual absorption described efpeglenatide PK data adequately.
In plain wordsIn participants with diabetes or obesity, the model described efpeglenatide concentrations adequately.
Peptide
Efpeglenatide
Outcome
Not applicablePopulation PK model fit
Study
n: not reported in source
Outcome group
Pharmacokinetics · Pharmacology
Studied dose
Dose not stated
Source sentences
Summary
A two-compartment model with dual absorption pathways adequately described the data.
1 context sentence(design, population, supporting numbers)
Summary · context
Pooled PK data from six clinical studies in participants with type 2 diabetes or obesity were analyzed using nonlinear mixed-effects modeling (NONMEM).
Show in the study text Report a problemFND-4140344901
02HumanObservational studyPharmacokinetics
In participants with diabetes or obesity, body weight and disease status influenced efpeglenatide absorption and clearance in the population PK model.
In plain wordsIn participants with diabetes or obesity, body weight and disease status influenced how efpeglenatide was absorbed and cleared.
Peptide
Efpeglenatide
Outcome
Direction not reportedAbsorption and clearance covariates
Study
n: not reported in source
Outcome group
Pharmacokinetics · Pharmacology
Studied dose
Dose not stated
Source sentences
Summary
Body weight and disease status influenced absorption and clearance;
1 context sentence(design, population, supporting numbers)
Summary · context
Pooled PK data from six clinical studies in participants with type 2 diabetes or obesity were analyzed using nonlinear mixed-effects modeling (NONMEM).
Show in the study text Report a problemFND-4140344902

Studies that did not test the peptide alone3

In this study, Efpeglenatide was a lab tool or a carrier, part of a mix, or the subject of a lab method. These results are not evidence about taking Efpeglenatide.

03Computer modelNot a test of Efpeglenatide aloneIn silicoPharmacokinetics
In simulations, predicted efpeglenatide exposure differences across weight and demographic subgroups were modest and within conventional bioequivalence limits.
In plain wordsComputer models predicted modest efpeglenatide exposure differences across weight and demographic groups, within conventional bioequivalence limits.
Peptide
Efpeglenatide
Outcome
Not applicablePredicted subgroup exposure
Study
n: not reported in source
Outcome group
Pharmacokinetics · Pharmacology
Source sentences
Summary
Body weight and disease status influenced absorption and clearance; however, predicted exposure differences across weight percentiles and demographic subgroups were modest and within conventional bioequivalence limits.
1 context sentence(design, population, supporting numbers)
Summary · context
Pooled PK data from six clinical studies in participants with type 2 diabetes or obesity were analyzed using nonlinear mixed-effects modeling (NONMEM).
In this study, Efpeglenatide was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Efpeglenatide.
Show in the study text Report a problemFND-4140344904
04Computer modelNot a test of Efpeglenatide aloneIn silicoPharmacokinetics
Simulations suggested approximately dose-proportional efpeglenatide exposure increases with once-weekly administration.
In plain wordsComputer models suggested efpeglenatide exposure increased approximately in proportion to the weekly dose.
Peptide
Efpeglenatide
Outcome
IncreaseSimulated dose proportionality
Study
n: not reported in source
Outcome group
Pharmacokinetics · Pharmacology
Source sentences
Summary
Simulations suggested approximately dose-proportional increases across the evaluated dose range with once-weekly administration and supported the feasibility of stepwise dose-escalation.
1 context sentence(design, population, supporting numbers)
Summary · context
Pooled PK data from six clinical studies in participants with type 2 diabetes or obesity were analyzed using nonlinear mixed-effects modeling (NONMEM).
In this study, Efpeglenatide was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Efpeglenatide.
Show in the study text Report a problemFND-4140344905
05Computer modelNot a test of Efpeglenatide aloneIn silicoPharmacokinetics
Simulations supported the feasibility of stepwise efpeglenatide dose escalation.
In plain wordsComputer models supported the feasibility of increasing efpeglenatide doses in steps.
Peptide
Efpeglenatide
Outcome
Not applicableStepwise dose escalation feasibility
Study
n: not reported in source
Outcome group
Pharmacokinetics · Pharmacology
Source sentences
Summary
Simulations suggested approximately dose-proportional increases across the evaluated dose range with once-weekly administration and supported the feasibility of stepwise dose-escalation.
1 context sentence(design, population, supporting numbers)
Summary · context
Pooled PK data from six clinical studies in participants with type 2 diabetes or obesity were analyzed using nonlinear mixed-effects modeling (NONMEM).
In this study, Efpeglenatide was a lab tool or a carrier, part of a mix, or the subject of a lab method. This result is not evidence about taking Efpeglenatide.
Show in the study text Report a problemFND-4140344906

AI wrote and checked these results. AI can make mistakes, so check important results against the source.

Version history

PepBank keeps every version of the data on this study. Status changes from Retraction Watch, Europe PMC and Crossref are listed with their source.

Version 2Current
27 Oct 2026, 18:20 UTC
Study results updated
Version 1
27 Oct 2026, 16:32 UTC
First added · source update from Europe PMC

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