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Peer-reviewedCC BY-NC-NDSignal transduction and targeted therapy

Real-world renoprotective effects of polyethylene glycol-loxenatide in type 2 diabetes: a multicenter, ambispective cohort study.

  • Junjun Ye1,2
  • Jilin Li1
  • Yongsong Chen3
  • Fengwu Chen3
  • Dan Zhu4
  • Chuangyan Zhang4
  • Qianyi Chen4,5
  • Yu Tian6
  • Shuhui Yang7
  • Wencan Xu3
  • Bin Xie1
  • Zhe-Sheng Chen8
1 more authors
  • Kaijian Hou9,10
10 affiliations
  1. 1Department of Cardiology, Second Affiliated Hospital of Shantou University Medical College, Shantou, China.
  2. 2Shantou University Medical College, Shantou, China.
  3. 3Department of Endocrinology and Metabolism, The first Affiliated Hospital of Shantou University Medical College, Shantou, China.
  4. 4Department of Endocrinology and Metabolism, Longhu People's Hospital, Shantou, China.
  5. 5School of Public Health, Shantou University, Shantou, China.
  6. 6Research Center, Huizhou Central People's Hospital, Guangdong Medical University, Huizhou, China.
  7. 7Department of Endocrinology and Metabolism, Shantou Central Hospital, Shantou, China.
  8. 8Department of Pharmaceutical Sciences, College of Pharmacy and Health Sciences, St. John's University, New York, NY, USA. [email protected].
  9. 9Department of Endocrinology and Metabolism, The first Affiliated Hospital of Shantou University Medical College, Shantou, China. [email protected].
  10. 10Department of Endocrinology and Metabolism, Longhu People's Hospital, Shantou, China. [email protected].
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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 therapy was associated with an attenuated risk of major renal events. Given the null findings in the matched cohort, the cardiovascular observations are exploratory and require randomized confirmation.

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Cite

BibTeXRIS
BibTeX
@article{ye2026realworld,
  title = {{Real-world renoprotective effects of polyethylene glycol-loxenatide in type 2 diabetes: a multicenter, ambispective cohort study.}},
  author = {Junjun Ye and Jilin Li and Yongsong Chen and Fengwu Chen and Dan Zhu and Chuangyan Zhang and Qianyi Chen and Yu Tian and Shuhui Yang and Wencan Xu and Bin Xie and Zhe-Sheng Chen and Kaijian Hou},
  journal = {Signal transduction and targeted therapy},
  year = {2026},
  month = oct,
  doi = {10.1038/s41392-026-02945-5},
  url = {https://europepmc.org/article/MED/42897130},
  note = {CC BY-NC-ND},
}
RIS
TY  - JOUR
TI  - Real-world renoprotective effects of polyethylene glycol-loxenatide in type 2 diabetes: a multicenter, ambispective cohort study.
AU  - Junjun Ye
AU  - Jilin Li
AU  - Yongsong Chen
AU  - Fengwu Chen
AU  - Dan Zhu
AU  - Chuangyan Zhang
AU  - Qianyi Chen
AU  - Yu Tian
AU  - Shuhui Yang
AU  - Wencan Xu
AU  - Bin Xie
AU  - Zhe-Sheng Chen
AU  - Kaijian Hou
PY  - 2026
DA  - 2026/10/20
JO  - Signal transduction and targeted therapy
DO  - 10.1038/s41392-026-02945-5
UR  - https://europepmc.org/article/MED/42897130
AB  - 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 therapy was associated with an attenuated risk of major renal events. Given the null findings in the matched cohort, the cardiovascular observations are exploratory and require randomized confirmation.
SN  - 2095-9907
SN  - 2059-3635
ER  -