---
title: "VCT220 oral nonpeptide GLP-1RA for obesity: phase II randomized trial results"
id: "pubmed-42595749"
canonical_url: "https://medichelpline.com/clinical-feed/pubmed-42595749"
content_type: "clinical_feed_article"
specialty: "Pharmacology"
source_name: "PubMed / NCBI"
source_url: "https://pubmed.ncbi.nlm.nih.gov/42595749/"
doi: "10.1038/s41392-026-02859-2"
published_at: "2026-08-14T00:00:00.000Z"
evidence_level: "Journal Article"
license: "CC-BY-NC-4.0 / Informational Use"
---
# VCT220 oral nonpeptide GLP-1RA for obesity: phase II randomized trial results
## Provenance & Clinical Metadata
- **Canonical URL:** https://medichelpline.com/clinical-feed/pubmed-42595749
- **Specialty:** [Pharmacology](https://medichelpline.com/clinical-feed/pharmacology.md)
- **Primary Source:** PubMed / NCBI
- **Source URL:** [Original Journal Publication](https://pubmed.ncbi.nlm.nih.gov/42595749/)
- **DOI:** [10.1038/s41392-026-02859-2](https://doi.org/10.1038%2Fs41392-026-02859-2)
- **Published At:** 2026-08-14T00:00:00.000Z
- **Evidence Rating:** Journal Article
## Executive GIST (TL;DR)
- This multicenter, randomized, double-blind, placebo-controlled phase II trial evaluated **VCT220**, an oral nonpeptide **GLP-1 receptor agonist (GLP-1RA)**, for obesity treatment over 16 weeks. - Trials were conducted at 13 sites in China and were registered as CTR20233978 and NCT06569355. - Adults aged 18–75 with overweight (BMI 24–28 kg/m² plus ≥1 comorbidity) or obesity (BMI ≥28 kg/m²) were enrolled; 250 participants were randomized (189 to VCT220, 61 to placebo) in a 3:1 ratio. - VCT220 was dosed once daily at 80 mg, 120 mg, or 160 mg with either slow titration (ST) or fast titration (FT) regimens; all participants received lifestyle counselling. - The primary endpoint was percent change in body weight from baseline to week 16. - At week 16, mean weight reduction with VCT220 ranged from **−5.75%** (80 mg) to **−9.73%** (160 mg fast titration) versus **−1.61%** with placebo (all p < 0.001). - The proportion of participants achieving ≥5% weight loss ranged from **55.4%** (80 mg) to **90.3%** (160 mg slow titration) with VCT220, compared with **13.1%** with placebo. - VCT220 produced improvements in **HbA1c**, fasting insulin, and blood pressure in addition to weight loss. - Adverse events were mainly mild-to-moderate gastrointestinal symptoms, most frequent during titration, and seldom caused treatment discontinuation. - The study was funded by Chengdu Vincentage Pharma Co., Ltd.; company employees were coauthors and conflicts of interest were disclosed. - Authors conclude that once-daily oral VCT220 delivered rapid, clinically meaningful weight loss with metabolic benefits over 16 weeks and supports further global phase III evaluation.
## Clinical Analysis & Structured Key Points
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Ltd., Chengdu, China."), [Mei Liu](https://pubmed.ncbi.nlm.nih.gov/?term=Liu+M&cauthor_id=42595749)[ 3 ](https://pubmed.ncbi.nlm.nih.gov/42595749/#full-view-affiliation-3 "Chengdu Vincentage Pharma Co. Ltd., Chengdu, China."), [Xianghua Zhang](https://pubmed.ncbi.nlm.nih.gov/?term=Zhang+X&cauthor_id=42595749)[ 4 ](https://pubmed.ncbi.nlm.nih.gov/42595749/#full-view-affiliation-4 "Department of General Medicine, Yueyang Central Hospital, Yueyang, Hunan, China."), [Chao Meng](https://pubmed.ncbi.nlm.nih.gov/?term=Meng+C&cauthor_id=42595749)[ 5 ](https://pubmed.ncbi.nlm.nih.gov/42595749/#full-view-affiliation-5 "Department of General Medicine, Central Hospital Affiliated to Shandong First Medical University, Jinan, China.") Affiliations Expand ### Affiliations * 1 Department of Endocrinology, Peking University People's Hospital, Beijing, China. jiln@bjmu.edu.cn. * 2 Department of Endocrinology, Peking University People's Hospital, Beijing, China. * 3 Chengdu Vincentage Pharma Co. Ltd., Chengdu, China. * 4 Department of General Medicine, Yueyang Central Hospital, Yueyang, Hunan, China. * 5 Department of General Medicine, Central Hospital Affiliated to Shandong First Medical University, Jinan, China. # Contributed equally. * PMID: **42595749** * DOI: [ 10.1038/s41392-026-02859-2 ](https://doi.org/10.1038/s41392-026-02859-2) Item in Clipboard Clinical Trial # Oral nonpeptide GLP-1 receptor agonist VCT220 for obesity treatment: a randomized, double-blind, phase II trial Linong Ji et al. Signal Transduct Target Ther. 2026. Show details Display options Display options Format Abstract PubMed PMID Signal Transduct Target Ther Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Signal+Transduct+Target+Ther%22%5Bjour%5D&sort=date&sort_order=desc) * [ Search in NLM Catalog ](https://www.ncbi.nlm.nih.gov/nlmcatalog?term=%22Signal+Transduct+Target+Ther%22%5BTitle+Abbreviation%5D) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42595749/) . 2026 Aug 14;11(1):325. doi: 10.1038/s41392-026-02859-2. ### Authors [Linong Ji](https://pubmed.ncbi.nlm.nih.gov/?term=Ji+L&cauthor_id=42595749)[#](https://pubmed.ncbi.nlm.nih.gov/42595749/#short-view-equal-contrib-explanation "Contributed equally")[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42595749/#short-view-affiliation-1 "Department of Endocrinology, Peking University People's Hospital, Beijing, China. jiln@bjmu.edu.cn."), [Leili Gao](https://pubmed.ncbi.nlm.nih.gov/?term=Gao+L&cauthor_id=42595749)[#](https://pubmed.ncbi.nlm.nih.gov/42595749/#short-view-equal-contrib-explanation "Contributed equally")[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42595749/#short-view-affiliation-2 "Department of Endocrinology, Peking University People's Hospital, Beijing, China."), [Ben Li](https://pubmed.ncbi.nlm.nih.gov/?term=Li+B&cauthor_id=42595749)[ 3 ](https://pubmed.ncbi.nlm.nih.gov/42595749/#short-view-affiliation-3 "Chengdu Vincentage Pharma Co. Ltd., Chengdu, China."), [Mei Liu](https://pubmed.ncbi.nlm.nih.gov/?term=Liu+M&cauthor_id=42595749)[ 3 ](https://pubmed.ncbi.nlm.nih.gov/42595749/#short-view-affiliation-3 "Chengdu Vincentage Pharma Co. Ltd., Chengdu, China."), [Xianghua Zhang](https://pubmed.ncbi.nlm.nih.gov/?term=Zhang+X&cauthor_id=42595749)[ 4 ](https://pubmed.ncbi.nlm.nih.gov/42595749/#short-view-affiliation-4 "Department of General Medicine, Yueyang Central Hospital, Yueyang, Hunan, China."), [Chao Meng](https://pubmed.ncbi.nlm.nih.gov/?term=Meng+C&cauthor_id=42595749)[ 5 ](https://pubmed.ncbi.nlm.nih.gov/42595749/#short-view-affiliation-5 "Department of General Medicine, Central Hospital Affiliated to Shandong First Medical University, Jinan, China.") ### Affiliations * 1 Department of Endocrinology, Peking University People's Hospital, Beijing, China. jiln@bjmu.edu.cn. * 2 Department of Endocrinology, Peking University People's Hospital, Beijing, China. * 3 Chengdu Vincentage Pharma Co. Ltd., Chengdu, China. * 4 Department of General Medicine, Yueyang Central Hospital, Yueyang, Hunan, China. * 5 Department of General Medicine, Central Hospital Affiliated to Shandong First Medical University, Jinan, China. # Contributed equally. * PMID: **42595749** * DOI: [ 10.1038/s41392-026-02859-2 ](https://doi.org/10.1038/s41392-026-02859-2) Item in Clipboard Cite Display options Display options Format Abstract PubMed PMID ## Abstract VCT220 is a novel nonpeptide, orally available glucagon-like peptide-1 receptor agonist (GLP-1RA) designed to reduce the complex administration of injectable GLP-1RAs and the limited bioavailability of on-marketing oral agents for obesity care. We conducted a multicenter, randomized, double-blind, placebo-controlled, phase II trial (Registration no. CTR20233978 and [NCT06569355](http://clinicaltrials.gov/show/NCT06569355 "See in ClinicalTrials.gov")) across 13 sites in China. Adults aged 18-75 years with overweight (BMI 24-28 kg/m² plus ≥ 1 comorbidity) or obesity (BMI ≥ 28 kg/m²) were randomly assigned (3:1) to receive once-daily VCT220 (80 mg, 120 mg, or 160 mg with slow or fast titration) or placebo for 16 weeks, alongside lifestyle counselling. The primary endpoint was the percentage change in body weight from baseline to week 16. Two-hundred and fifty participants were randomized (61 to placebo, 189 to VCT220). At week 16, mean body weight decreased by -5.75% (80 mg) to -9.73% (160 mg-FT) versus -1.61% with placebo (all p < 0.001). The proportion achieving ≥5% weight loss ranged from 55.4% (80 mg) to 90.3% (160 mg-ST) with VCT220 versus 13.1% with placebo. VCT220 also improved HbA1c, fasting insulin, and blood pressure. Adverse events were mainly mild-to-moderate gastrointestinal events, most common during titration, and rarely led to discontinuation. VCT220, a once-daily oral nonpeptide GLP-1RA, produced rapid and clinically meaningful weight loss with metabolic benefits over 16 weeks, showing a tolerability profile consistent with the class. These findings support further global phase III evaluation to further verify the efficacy and safety of VCT220 as well as potential cardiometabolic benefits. © 2026. The Author(s). [PubMed Disclaimer](https://pubmed.ncbi.nlm.nih.gov/disclaimer/) ## Conflict of interest statement Competing interests: LNJ is the leading PI of this study, which is funded by Chengdu Vincentage Pharma Co., Ltd. BL is a full-time employee of and stockholder at Chengdu Vincentage Pharma Co., Ltd. ML is a full-time employee of Chengdu Vincentage. Others have nothing to disclose. ## References 1. 1. Wharton, S. et al. Obesity in adults: a clinical practice guideline. CMAJ. 192, E875–E891 (2020). - [DOI](https://doi.org/10.1503/cmaj.191707) - [PubMed](https://pubmed.ncbi.nlm.nih.gov/32753461/) - [PMC](https://pmc.ncbi.nlm.nih.gov/articles/7828878/) 2. 1. Pan, X.-F., Wang, L. & Pan, A. Epidemiology and determinants of obesity in China. Lancet Diab. Endocrinol. 9, 373–392 (2021). - [DOI](https://doi.org/10.1016/s2213-8587\(21\)00045-0) 3. 1. National Health Commission of the People’s Republic of China Department of Medical Administration. Chinese diagnosis and treatment guideline for obesity (2024 edition) (in Chinese). Peking. Union Med. J. 16, 90–108 (2025). 4. 1. Wong, H. J. et al. Efficacy of GLP-1 receptor agonists on weight loss, BMI, and waist circumference for patients with obesity or overweight: a systematic review, meta-analysis, and meta-regression of 47 randomized controlled trials. Diab. Care 48, 292–300 (2025). - [DOI](https://doi.org/10.2337/dc24-1678) 5. 1. Wang, W. et al. Efficacy and safety of oral semaglutide monotherapy vs placebo in a predominantly chinese population with type 2 diabetes (PIONEER 11): a double-blind, phase IIIa, randomised trial. Diabetologia 67, 1783–1799 (2024). - [DOI](https://doi.org/10.1007/s00125-024-06142-3) - [PubMed](https://pubmed.ncbi.nlm.nih.gov/38985162/) - [PMC](https://pmc.ncbi.nlm.nih.gov/articles/11410837/) Show all 24 references ## Publication types * Randomized Controlled Trial Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Randomized+Controlled+Trial%22%5Bpt%5D&sort=date&sort_order=desc) * [ Search in MeSH ](https://www.ncbi.nlm.nih.gov/mesh?term=Randomized+Controlled+Trial) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42595749/) * Clinical Trial, Phase II Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Clinical+Trial%2C+Phase+II%22%5Bpt%5D&sort=date&sort_order=desc) * [ Search in MeSH ](https://www.ncbi.nlm.nih.gov/mesh?term=Clinical+Trial%2C+Phase+II) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42595749/) * Multicenter Study Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Multicenter+Study%22%5Bpt%5D&sort=date&sort_order=desc) * [ Search in MeSH ](https://www.ncbi.nlm.nih.gov/mesh?term=Multicenter+Study) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42595749/) ## MeSH terms * Administration, Oral Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Administration%2C+Oral%22%5BMeSH%5D&sort=date&sort_order=desc) * [ Search in MeSH ](https://www.ncbi.nlm.nih.gov/mesh?term=Administration%2C+Oral) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42595749/) * Adolescent Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Adolescent%22%5BMeSH%5D&sort=date&sort_order=desc) * [ Search in MeSH ](https://www.ncbi.nlm.nih.gov/mesh?term=Adolescent) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42595749/) * Adult Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Adult%22%5BMeSH%5D&sort=date&sort_order=desc) * [ Search in MeSH ](https://www.ncbi.nlm.nih.gov/mesh?term=Adult) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42595749/) * Aged Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Aged%22%5BMeSH%5D&sort=date&sort_order=desc) * [ Search in MeSH ](https://www.ncbi.nlm.nih.gov/mesh?term=Aged) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42595749/) * Double-Blind Method Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Double-Blind+Method%22%5BMeSH%5D&sort=date&sort_order=desc) * [ Search in MeSH ](https://www.ncbi.nlm.nih.gov/mesh?term=Double-Blind+Method) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42595749/) * Female Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Female%22%5BMeSH%5D&sort=date&sort_order=desc) * [ Search in MeSH ](https://www.ncbi.nlm.nih.gov/mesh?term=Female) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42595749/) * Glucagon-Like Peptide-1 Receptor / genetics Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Glucagon-Like+Peptide-1+Receptor%2Fgenetics%22%5BMeSH%5D&sort=date&sort_order=desc) * [ Search in MeSH ](https://www.ncbi.nlm.nih.gov/mesh?term=Glucagon-Like+Peptide-1+Receptor) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42595749/) * Glucagon-Like Peptide-1 Receptor Agonists* Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Glucagon-Like+Peptide-1+Receptor+Agonists%22%5BMAJR%5D&sort=date&sort_order=desc) * [ Search in MeSH ](https://www.ncbi.nlm.nih.gov/mesh?term=Glucagon-Like+Peptide-1+Receptor+Agonists) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42595749/) * Humans Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Humans%22%5BMeSH%5D&sort=date&sort_order=desc) * [ Search in MeSH ](https://www.ncbi.nlm.nih.gov/mesh?term=Humans) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42595749/) * Male Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Male%22%5BMeSH%5D&sort=date&sort_order=desc) * [ Search in MeSH ](https://www.ncbi.nlm.nih.gov/mesh?term=Male) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42595749/) * Middle Aged Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Middle+Aged%22%5BMeSH%5D&sort=date&sort_order=desc) * [ Search in MeSH ](https://www.ncbi.nlm.nih.gov/mesh?term=Middle+Aged) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42595749/) * Obesity* / drug therapy Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Obesity%2Fdrug+therapy%22%5BMAJR%5D&sort=date&sort_order=desc) * [ Search in MeSH ](https://www.ncbi.nlm.nih.gov/mesh?term=Obesity) * [ Add to Search ](https://pubmed.ncbi.nlm.nih.gov/42595749/) * Obesity* / genetics Actions * [ Search in PubMed ](https://pubmed.ncbi.nlm.nih.gov/?term=%22Obesity%2Fgenetics%22%5BMAJR%5D&sort=date&sort_order=desc) * [ Search in MeSH ](https://www.ncbi.
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