Evidence map›Paper›PMID 40175670›Full record

Trial reportBioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy2025

First-in-Human Study on Tolerability, Pharmacokinetics, and Pharmacodynamics of Single Escalating Doses of HEC88473, a Novel Dual GLP-1 and FGF21 Receptor Agonist in Healthy and Obese Chinese Subjects.

Hong Zhang, Qianqian Li, Hong Chen, Lingfeng Guo, Jing Li, Can Xie, Jiangyu Yan, Yanhua Ding

Registry-linked trialAbstract readClinical Trial, Phase IRandomized Controlled Trial
PubMed Publisher
In one paragraph

Trial report in BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT05943886 (A Phase 1, Randomised, Double-blind, Placebo-controlled, Single and Multiple Dose Study to Investigate Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of HEC88473 Injection in Healthy Subjects, Obese Subjects and T2DM Subjects), which is not on this map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing 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.

NCT05943886 phase1completednot on this map

A Phase 1, Randomised, Double-blind, Placebo-controlled, Single and Multiple Dose Study to Investigate Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of HEC88473 Injection in Healthy Subjects, Obese Subjects and T2DM Subjects

TypeinterventionalSponsorDongguan HEC Biopharmaceutical R&D Co., Ltd.Ran2021 to 2023Enrolled164ConditionsHealthy Subjects, Obesity, T2DM (Type 2 Diabetes Mellitus)ArmsHEC88473 injection, Placebo
3 · Its place in the literature

Who cites it

2 citing papers in PubMed.

  1. Article
  2. Review
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

8 authors.

Hong ZhangPhase I Clinical Research Center, The First Hospital of Jilin University, Changchun, 130021, Jilin, China.
Qianqian LiPhase I Clinical Research Center, The First Hospital of Jilin University, Changchun, 130021, Jilin, China.
Hong ChenPhase I Clinical Research Center, The First Hospital of Jilin University, Changchun, 130021, Jilin, China.
Lingfeng GuoDongguan HEC Biopharmaceutical R&D Co., Ltd, Dongguan, China.
Jing LiDongguan HEC Biopharmaceutical R&D Co., Ltd, Dongguan, China.
Can XieDongguan HEC Biopharmaceutical R&D Co., Ltd, Dongguan, China.
Jiangyu YanDongguan HEC Biopharmaceutical R&D Co., Ltd, Dongguan, China.
Yanhua DingPhase I Clinical Research Center, The First Hospital of Jilin University, Changchun, 130021, Jilin, China. dingyanh@jlu.edu.cn.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundHEC88473 is a novel long-acting dual agonist of glucagon-like peptide 1 (GLP-1) and fibroblast growth factor 21 (FGF21) receptors. It is a Fc fusion protein containing a fibroblast growth factor 21 and a GLP-1 moiety, fused to the N-terminal and C-terminal of the Fc fragment, respectively.

objectivesThis study aimed to evaluate the clinical safety, tolerability, pharmacokinetics, and pharmacodynamics of HEC88473.

methodsThe clinical safety, tolerability, pharmacokinetics, and preliminary pharmacodynamics of HEC88473 (0.5-62.9 mg) were evaluated in a phase I, single-ascending dose trial with healthy and obese subjects. Serum glucose, lipid, and adiponectin levels were evaluated.

resultsHEC88473 was slowly absorbed and metabolized into Fc-GLP-1 and Fc-FGF21 after dosing. In healthy participants, the median times to observed maximum serum concentration of HEC88473, Fc-GLP-1, and Fc-FGF21 were all in the range of 12.00-14.00 h, and their geomean half-lives were 16.2-22.6, 66.5-119.5, and 28.4-41.6 h, respectively. Their systemic exposure increased slightly more than proportionally to the dose. In healthy subjects, serum glucose decreased from baseline (day 1) in the oral glucose tolerance test at days 3 and 7 after HEC88473 administration with doses ≥ 5.1 mg, and the largest reduction occured in the 47.6-mg dose group, which was -1.829 mmol/L after baseline and placebo adjustment. At doses of ≥ 10.2 mg, adiponectin levels showed an upward trend with the dose and treatment time, and the average percentage increase of adiponectin from baseline was up to 90.71% in the 62.9-mg dose group. At doses of ≥ 17.0 mg, triglyceride levels showed a significant reduction from baseline in a certain dose-dependent manner, and the average percentage of triglyceride decrease from baseline was up to - 43.01% in the 62.9-mg dose group. HEC88473 was well tolerated, with the majority of treatment-related adverse events being gastrointestinal disorders of mild severity.

conclusionsHEC88473 is well tolerated in healthy and obese subjects, and it shows glucose-lowering and lipid-lowering efficacies. The data support further clinical evaluations of HEC88473 for the treatment of metabolic diseases. CLINICAL

trial registrationThis study was registered at ClinicalTrials.gov (registration number: NCT05943886).

Indexed as

Glucagon-Like Peptide-1 Receptor AgonistsObesityReceptors, Fibroblast Growth FactorRecombinant Fusion ProteinsAdiponectinAdultBlood GlucoseDose-Response Relationship, DrugEast Asian PeopleFemaleFibroblast Growth FactorsGlucagon-Like Peptide 1Healthy VolunteersHumansImmunoglobulin Fc FragmentsMaleAdiponectinBlood GlucoseFGF21 protein, humanFibroblast Growth FactorsGlucagon-Like Peptide 1Glucagon-Like Peptide-1 Receptor AgonistsImmunoglobulin Fc FragmentsReceptors, Fibroblast Growth FactorRecombinant Fusion Proteins

Identifiers

PMID40175670

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Registered trials

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.