ArticleSignal transduction and targeted therapy2026
Real-world renoprotective effects of polyethylene glycol-loxenatide in type 2 diabetes: a multicenter, ambispective cohort study.
Article in Signal transduction and targeted therapy, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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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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