---
title: "Renal outcomes with polyethylene glycol-loxenatide in T2DM: multicenter ambispective cohort"
id: "pubmed-42897130"
canonical_url: "https://medichelpline.com/clinical-feed/pubmed-42897130"
content_type: "clinical_feed_article"
specialty: "Pharmacology"
source_name: "PubMed / NCBI"
source_url: "https://pubmed.ncbi.nlm.nih.gov/42897130/"
doi: "10.1038/s41392-026-02945-5"
published_at: "2026-10-20T00:00:00.000Z"
evidence_level: "Journal Article"
license: "CC-BY-NC-4.0 / Informational Use"
---
# Renal outcomes with polyethylene glycol-loxenatide in T2DM: multicenter ambispective cohort
## Provenance & Clinical Metadata
- **Canonical URL:** https://medichelpline.com/clinical-feed/pubmed-42897130
- **Specialty:** [Pharmacology](https://medichelpline.com/clinical-feed/pharmacology.md)
- **Primary Source:** PubMed / NCBI
- **Source URL:** [Original Journal Publication](https://pubmed.ncbi.nlm.nih.gov/42897130/)
- **DOI:** [10.1038/s41392-026-02945-5](https://doi.org/10.1038%2Fs41392-026-02945-5)
- **Published At:** 2026-10-20T00:00:00.000Z
- **Evidence Rating:** Journal Article
## Executive GIST (TL;DR)
- The study enrolled 3,305 patients with **type 2 diabetes mellitus** plus renal impairment and elevated cardiovascular risk across six Chinese tertiary centers; median follow-up was 36.4 months. - Investigators used an ambispective cohort design and extracted clinical data through an artificial intelligence–enhanced pipeline; the trial is registered as ChiCTR2300073001. - Co-primary statistical approaches included multivariable-adjusted Cox regression across the full cohort and a 1:1 propensity score-matched analysis (332 patients per group). - Landmark analyses at 6 and 12 months were prespecified to address potential immortal time bias; both landmarks showed progressive signal. - In the original cohort, treatment with **polyethylene glycol-loxenatide** correlated with a lower risk of the primary **kidney composite outcome** (HR 0.49; 95% CI, 0.25–0.95; P = 0.035). - The propensity score–matched cohort corroborated the renal finding (HR 0.44; 95% CI, 0.20–0.97; P = 0.043). - Landmark results indicated continued risk reduction at 6 months (HR 0.40; 95% CI, 0.19–0.84) and at 12 months (HR 0.33; 95% CI, 0.14–0.75). - A lower rate of **3-point major adverse cardiovascular events** (MACE) appeared in the unmatched analysis (HR 0.60; 95% CI, 0.43–0.85; P = 0.004), but this association did not persist after propensity score matching (HR 0.92; 95% CI, 0.57–1.48; P = 0.735). - The abstract truncates before a final study conclusion; the source did not report the complete concluding text within the provided abstract.
## Clinical Analysis & Structured Key Points
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Real-world renoprotective effects of polyethylene glycol-loxenatide in type 2 diabetes: a multicenter, ambispective cohort study [Junjun Ye](https://pubmed.ncbi.nlm.nih.gov/?term=Ye+J&cauthor_id=42897130)[#](https://pubmed.ncbi.nlm.nih.gov/42897130/#full-view-equal-contrib-explanation "Contributed equally")[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42897130/#full-view-affiliation-1 "Department of Cardiology, Second Affiliated Hospital of Shantou University Medical College, Shantou, China.")[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42897130/#full-view-affiliation-2 "Shantou University Medical College, Shantou, China."), [Jilin Li](https://pubmed.ncbi.nlm.nih.gov/?term=Li+J&cauthor_id=42897130)[#](https://pubmed.ncbi.nlm.nih.gov/42897130/#full-view-equal-contrib-explanation "Contributed equally")[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42897130/#full-view-affiliation-1 "Department of Cardiology, Second Affiliated Hospital of Shantou University Medical College, Shantou, China."), [Yongsong Chen](https://pubmed.ncbi.nlm.nih.gov/?term=Chen+Y&cauthor_id=42897130)[#](https://pubmed.ncbi.nlm.nih.gov/42897130/#full-view-equal-contrib-explanation "Contributed equally")[ 3 ](https://pubmed.ncbi.nlm.nih.gov/42897130/#full-view-affiliation-3 "Department of Endocrinology and Metabolism, The first Affiliated Hospital of Shantou University Medical College, Shantou, China."), [Fengwu Chen](https://pubmed.ncbi.nlm.nih.gov/?term=Chen+F&cauthor_id=42897130)[ 3 ](https://pubmed.ncbi.nlm.nih.gov/42897130/#full-view-affiliation-3 "Department of Endocrinology and Metabolism, The first Affiliated Hospital of Shantou University Medical College, Shantou, China."), [Dan Zhu](https://pubmed.ncbi.nlm.nih.gov/?term=Zhu+D&cauthor_id=42897130)[ 4 ](https://pubmed.ncbi.nlm.nih.gov/42897130/#full-view-affiliation-4 "Department of Endocrinology and Metabolism, Longhu People's Hospital, Shantou, China."), [Chuangyan Zhang](https://pubmed.ncbi.nlm.nih.gov/?term=Zhang+C&cauthor_id=42897130)[ 4 ](https://pubmed.ncbi.nlm.nih.gov/42897130/#full-view-affiliation-4 "Department of Endocrinology and Metabolism, Longhu People's Hospital, Shantou, China."), [Qianyi Chen](https://pubmed.ncbi.nlm.nih.gov/?term=Chen+Q&cauthor_id=42897130)[ 4 ](https://pubmed.ncbi.nlm.nih.gov/42897130/#full-view-affiliation-4 "Department of Endocrinology and Metabolism, Longhu People's Hospital, Shantou, China.")[ 5 ](https://pubmed.ncbi.nlm.nih.gov/42897130/#full-view-affiliation-5 "School of Public Health, Shantou University, Shantou, China."), [Yu Tian](https://pubmed.ncbi.nlm.nih.gov/?term=Tian+Y&cauthor_id=42897130)[ 6 ](https://pubmed.ncbi.nlm.nih.gov/42897130/#full-view-affiliation-6 "Research Center, Huizhou Central People's Hospital, Guangdong Medical University, Huizhou, China."), [Shuhui Yang](https://pubmed.ncbi.nlm.nih.gov/?term=Yang+S&cauthor_id=42897130)[ 7 ](https://pubmed.ncbi.nlm.nih.gov/42897130/#full-view-affiliation-7 "Department of Endocrinology and Metabolism, Shantou Central Hospital, Shantou, China."), [Wencan Xu](https://pubmed.ncbi.nlm.nih.gov/?term=Xu+W&cauthor_id=42897130)[ 3 ](https://pubmed.ncbi.nlm.nih.gov/42897130/#full-view-affiliation-3 "Department of Endocrinology and Metabolism, The first Affiliated Hospital of Shantou University Medical College, Shantou, China."), [Bin Xie](https://pubmed.ncbi.nlm.nih.gov/?term=Xie+B&cauthor_id=42897130)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42897130/#full-view-affiliation-1 "Department of Cardiology, Second Affiliated Hospital of Shantou University Medical College, Shantou, China."), [Zhe-Sheng Chen](https://pubmed.ncbi.nlm.nih.gov/?term=Chen+ZS&cauthor_id=42897130)[ 8 ](https://pubmed.ncbi.nlm.nih.gov/42897130/#full-view-affiliation-8 "Department of Pharmaceutical Sciences, College of Pharmacy and Health Sciences, St. John's University, New York, NY, USA. chenz@stjohns.edu."), [Kaijian Hou](https://pubmed.ncbi.nlm.nih.gov/?term=Hou+K&cauthor_id=42897130)[ 9 ](https://pubmed.ncbi.nlm.nih.gov/42897130/#full-view-affiliation-9 "Department of Endocrinology and Metabolism, The first Affiliated Hospital of Shantou University Medical College, Shantou, China. kaijianhou@126.com.")[ 10 ](https://pubmed.ncbi.nlm.nih.gov/42897130/#full-view-affiliation-10 "Department of Endocrinology and Metabolism, Longhu People's Hospital, Shantou, China. kaijianhou@126.com.") Affiliations Expand ### Affiliations * 1 Department of Cardiology, Second Affiliated Hospital of Shantou University Medical College, Shantou, China. * 2 Shantou University Medical College, Shantou, China. * 3 Department of Endocrinology and Metabolism, The first Affiliated Hospital of Shantou University Medical College, Shantou, China. * 4 Department of Endocrinology and Metabolism, Longhu People's Hospital, Shantou, China. * 5 School of Public Health, Shantou University, Shantou, China. * 6 Research Center, Huizhou Central People's Hospital, Guangdong Medical University, Huizhou, China. * 7 Department of Endocrinology and Metabolism, Shantou Central Hospital, Shantou, China. * 8 Department of Pharmaceutical Sciences, College of Pharmacy and Health Sciences, St. John's University, New York, NY, USA. chenz@stjohns.edu. * 9 Department of Endocrinology and Metabolism, The first Affiliated Hospital of Shantou University Medical College, Shantou, China. kaijianhou@126.com. * 10 Department of Endocrinology and Metabolism, Longhu People's Hospital, Shantou, China. kaijianhou@126.com. # Contributed equally. * PMID: **42897130** * DOI: [ 10.1038/s41392-026-02945-5 ](https://doi.org/10.1038/s41392-026-02945-5) Item in Clipboard Multicenter Study # Real-world renoprotective effects of polyethylene glycol-loxenatide in type 2 diabetes: a multicenter, ambispective cohort study Junjun Ye 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/42897130/) . 2026 Oct 20;11(1):456. doi: 10.1038/s41392-026-02945-5. ### Authors [Junjun Ye](https://pubmed.ncbi.nlm.nih.gov/?term=Ye+J&cauthor_id=42897130)[#](https://pubmed.ncbi.nlm.nih.gov/42897130/#short-view-equal-contrib-explanation "Contributed equally")[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42897130/#short-view-affiliation-1 "Department of Cardiology, Second Affiliated Hospital of Shantou University Medical College, Shantou, China.")[ 2 ](https://pubmed.ncbi.nlm.nih.gov/42897130/#short-view-affiliation-2 "Shantou University Medical College, Shantou, China."), [Jilin Li](https://pubmed.ncbi.nlm.nih.gov/?term=Li+J&cauthor_id=42897130)[#](https://pubmed.ncbi.nlm.nih.gov/42897130/#short-view-equal-contrib-explanation "Contributed equally")[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42897130/#short-view-affiliation-1 "Department of Cardiology, Second Affiliated Hospital of Shantou University Medical College, Shantou, China."), [Yongsong Chen](https://pubmed.ncbi.nlm.nih.gov/?term=Chen+Y&cauthor_id=42897130)[#](https://pubmed.ncbi.nlm.nih.gov/42897130/#short-view-equal-contrib-explanation "Contributed equally")[ 3 ](https://pubmed.ncbi.nlm.nih.gov/42897130/#short-view-affiliation-3 "Department of Endocrinology and Metabolism, The first Affiliated Hospital of Shantou University Medical College, Shantou, China."), [Fengwu Chen](https://pubmed.ncbi.nlm.nih.gov/?term=Chen+F&cauthor_id=42897130)[ 3 ](https://pubmed.ncbi.nlm.nih.gov/42897130/#short-view-affiliation-3 "Department of Endocrinology and Metabolism, The first Affiliated Hospital of Shantou University Medical College, Shantou, China."), [Dan Zhu](https://pubmed.ncbi.nlm.nih.gov/?term=Zhu+D&cauthor_id=42897130)[ 4 ](https://pubmed.ncbi.nlm.nih.gov/42897130/#short-view-affiliation-4 "Department of Endocrinology and Metabolism, Longhu People's Hospital, Shantou, China."), [Chuangyan Zhang](https://pubmed.ncbi.nlm.nih.gov/?term=Zhang+C&cauthor_id=42897130)[ 4 ](https://pubmed.ncbi.nlm.nih.gov/42897130/#short-view-affiliation-4 "Department of Endocrinology and Metabolism, Longhu People's Hospital, Shantou, China."), [Qianyi Chen](https://pubmed.ncbi.nlm.nih.gov/?term=Chen+Q&cauthor_id=42897130)[ 4 ](https://pubmed.ncbi.nlm.nih.gov/42897130/#short-view-affiliation-4 "Department of Endocrinology and Metabolism, Longhu People's Hospital, Shantou, China.")[ 5 ](https://pubmed.ncbi.nlm.nih.gov/42897130/#short-view-affiliation-5 "School of Public Health, Shantou University, Shantou, China."), [Yu Tian](https://pubmed.ncbi.nlm.nih.gov/?term=Tian+Y&cauthor_id=42897130)[ 6 ](https://pubmed.ncbi.nlm.nih.gov/42897130/#short-view-affiliation-6 "Research Center, Huizhou Central People's Hospital, Guangdong Medical University, Huizhou, China."), [Shuhui Yang](https://pubmed.ncbi.nlm.nih.gov/?term=Yang+S&cauthor_id=42897130)[ 7 ](https://pubmed.ncbi.nlm.nih.gov/42897130/#short-view-affiliation-7 "Department of Endocrinology and Metabolism, Shantou Central Hospital, Shantou, China."), [Wencan Xu](https://pubmed.ncbi.nlm.nih.gov/?term=Xu+W&cauthor_id=42897130)[ 3 ](https://pubmed.ncbi.nlm.nih.gov/42897130/#short-view-affiliation-3 "Department of Endocrinology and Metabolism, The first Affiliated Hospital of Shantou University Medical College, Shantou, China."), [Bin Xie](https://pubmed.ncbi.nlm.nih.gov/?term=Xie+B&cauthor_id=42897130)[ 1 ](https://pubmed.ncbi.nlm.nih.gov/42897130/#short-view-affiliation-1 "Department of Cardiology, Second Affiliated Hospital of Shantou University Medical College, Shantou, China."), [Zhe-Sheng Chen](https://pubmed.ncbi.nlm.nih.gov/?term=Chen+ZS&cauthor_id=42897130)[ 8 ](https://pubmed.ncbi.nlm.nih.gov/42897130/#short-view-affiliation-8 "Department of Pharmaceutical Sciences, College of Pharmacy and Health Sciences, St. John's University, New York, NY, USA. chenz@stjohns.edu."), [Kaijian Hou](https://pubmed.ncbi.nlm.nih.gov/?term=Hou+K&cauthor_id=42897130)[ 9 ](https://pubmed.ncbi.nlm.nih.gov/42897130/#short-view-affiliation-9 "Department of Endocrinology and Metabolism, The first Affiliated Hospital of Shantou University Medical College, Shantou, China. kaijianhou@126.com.")[ 10 ](https://pubmed.ncbi.nlm.nih.gov/42897130/#short-view-affiliation-10 "Department of Endocrinology and Metabolism, Longhu People's Hospital, Shantou, China. kaijianhou@126.com.") ### Affiliations * 1 Department of Cardiology, Second Affiliated Hospital of Shantou University Medical College, Shantou, China. * 2 Shantou University Medical College, Shantou, China. * 3 Department of Endocrinology and Metabolism, The first Affiliated Hospital of Shantou University Medical College, Shantou, China. * 4 Department of Endocrinology and Metabolism, Longhu People's Hospital, Shantou, China. * 5 School of Public Health, Shantou University, Shantou, China. * 6 Research Center, Huizhou Central People's Hospital, Guangdong Medical University, Huizhou, China. * 7 Department of Endocrinology and Metabolism, Shantou Central Hospital, Shantou, China. * 8 Department of Pharmaceutical Sciences, College of Pharmacy and Health Sciences, St. John's University, New York, NY, USA. chenz@stjohns.edu. * 9 Department of Endocrinology and Metabolism, The first Affiliated Hospital of Shantou University Medical College, Shantou, China. kaijianhou@126.com. * 10 Department of Endocrinology and Metabolism, Longhu People's Hospital, Shantou, China. kaijianhou@126.com. # Contributed equally. * PMID: **42897130** * DOI: [ 10.1038/s41392-026-02945-5 ](https://doi.org/10.1038/s41392-026-02945-5) Item in Clipboard Cite Display options Display options Format Abstract PubMed PMID Linked Discoveries ## Abstract Patients with type 2 diabetes mellitus and chronic kidney disease face persistent risks despite standard care. Polyethylene glycol-loxenatide lacks real-world renoprotective evidence in high-risk Chinese populations relative to non-incretin-based standard care. This multicenter, ambispective cohort study enrolled 3305 patients with type 2 diabetes mellitus, renal impairment, and elevated cardiovascular risk at six Chinese tertiary institutions (median follow-up 36.4 months; trial registration: ChiCTR2300073001). Data were extracted via an artificial intelligence-enhanced pipeline. Co-primary analyzes comprised multivariable-adjusted Cox regression and 1:1 propensity score matching (332 per group); pre-specified landmark analyzes at 6 and 12 months addressed immortal time bias. Polyethylene glycol-loxenatide was associated with a reduced risk of the primary kidney composite outcome in the original cohort (hazard ratio [HR], 0.49; 95% CI, 0.25-0.95; P = 0.035), which was corroborated in the propensity score matched cohort (HR, 0.44; 95% CI, 0.20-0.97; P = 0.043) and progressive across 6-month (HR, 0.40; 95% CI, 0.19-0.84) and 12-month (HR, 0.33; 95% CI, 0.14-0.75) landmarks. While a reduction in 3-point major adverse cardiovascular events was observed in the unmatched cohort (HR, 0.60; 95% CI, 0.43-0.85; P = 0.004), this association was not sustained in the matched analysis (HR, 0.92; 95% CI, 0.57-1.48; P = 0.735). In conclusion, long-term therap
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