ArticleJournal of diabetes science and technology2026
Multisystem Outcomes of GLP-1 Receptor Agonists Versus Active Comparators in Type 2 Diabetes: A Multicenter Target Trial Emulation.
Article in Journal of diabetes science and technology, 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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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.
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11 authors.
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Abstract
backgroundMultisystem effects of glucagon-like peptide-1 receptor agonists (GLP-1RAs) beyond cardiometabolic outcomes are incompletely characterized against active comparators in type 2 diabetes (T2D). We compared GLP-1RA with sulfonylureas (SUs), sodium-glucose cotransporter-2 inhibitors (SGLT2is), and dipeptidyl peptidase-4 inhibitors (DPP4is) in adults with T2D.
methodIn a multicenter target trial emulation across 5 University of California academic medical centers (2012-2025) using harmonized electronic health record data, adults with T2D newly initiating GLP-1RA, SU, SGLT2i, or DPP4i were propensity score-matched 1-to-1 within site via least absolute shrinkage and selection operator (>11 000 covariates), with up to 5-year follow-up. We screened 181 prespecified incident outcomes across 15 body systems, pooling hazard ratios by random-effects meta-analysis. Robustness required leave-one-medical-center-out stability,
resultsAmong 70 982 matched adults, 118 robust associations were identified (65 for reduced risk and 53 for increased risk). Risk reductions were most consistent for cardiovascular outcomes, including myocarditis/cardiomyopathy (summary hazard ratio, 0.38 [95% CI, 0.32-0.44] vs SGLT2i), acute myocardial infarction (0.53 [0.42-0.66]), heart failure (0.71 [0.58-0.88] vs DPP4i), and thromboembolism (0.69-0.72), and for nephritis/nephrosis (0.73 [0.67-0.79]), nutritional anemia (0.70-0.81), coagulation disorders (0.73-0.81), and tobacco-related disorders (0.60 [0.49-0.74]). Risk increases were found for musculoskeletal conditions (22 associations); osteoarthritis 1.48 (1.29-1.68), stress fractures 1.68 (1.15-2.47), diverticular disease (1.18-1.33), sleep-wake disorders (1.27-1.54), and menopausal disorders (1.32-1.52).
conclusionsGlucagon-like peptide-1 receptor agonist initiation was associated with reduced cardiovascular, renal, hematologic, and tobacco-related risk, consistent with outcome trials. Increased risks for musculoskeletal, gastrointestinal, and sleep-wake disorders warrant monitoring as the clinical use of GLP-1RAs continues to expand.
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