{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,14]],"date-time":"2026-07-14T23:24:35Z","timestamp":1784071475536,"version":"3.55.0"},"reference-count":38,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2026,3,24]],"date-time":"2026-03-24T00:00:00Z","timestamp":1774310400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100015763","name":"Open Access Fund of the University of Szeged","doi-asserted-by":"publisher","award":["8396"],"award-info":[{"award-number":["8396"]}],"id":[{"id":"10.13039\/501100015763","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Medical Sciences"],"abstract":"<jats:p>Background: Hyperuricemia frequently coexists with type 2 diabetes mellitus (T2DM), contributing to a heterogeneous patient population. While previous analyses compared the overall longitudinal effects of allopurinol and SGLT2 inhibitors in this cohort, it remains unclear whether baseline metabolic heterogeneity modifies treatment response. This study aimed to determine whether data-driven metabolic clustering identifies phenotypic subgroups with prognostic or predictive relevance in hyperuricemic T2DM. Methods: In a retrospective cohort of 224 patients with T2DM and hyperuricemia, model-based clustering was applied to age, diabetes duration, body mass index (BMI), serum uric acid (sUA), HbA1c, eGFR, and sex. A sensitivity analysis excluded outliers, yielding 207 patients. Longitudinal trajectories of eGFR and sUA were assessed using linear mixed-effects models and individual slopes. Effect modification by cluster was tested via three-way interactions and analysis of covariance. Results: Clustering identified two groups with weak separation: an adipose\u2013metabolic cluster (n = 116; exclusively male, BMI 33.1 \u00b1 5.7 kg\/m2, sUA 478 \u00b1 62 \u00b5mol\/L) and a lean\u2013metabolic cluster (n = 91; exclusively female, BMI 31.3 \u00b1 6.0 kg\/m2, sUA 426 \u00b1 67 \u00b5mol\/L). Treatment-agnostic analyses showed no differences in eGFR and sUA slopes or in all-cause mortality across clusters. In both clusters, SGLT2 inhibitors yielded significantly more favourable eGFR slopes than allopurinol, while sUA reductions were comparable across treatments. No significant three-way interactions were detected. Conclusions: In this cohort, although baseline metabolic characteristics differ among patients, using the selected baseline variables, no clinically actionable treatment-relevant phenotypes were identified.<\/jats:p>","DOI":"10.3390\/medsci14020162","type":"journal-article","created":{"date-parts":[[2026,3,25]],"date-time":"2026-03-25T09:11:14Z","timestamp":1774429874000},"page":"162","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Cluster-Defined Metabolic Heterogeneity and Longitudinal Effects of Allopurinol and SGLT2 Inhibitors in Hyperuricemic Type 2 Diabetes"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-2508-6014","authenticated-orcid":false,"given":"Roland","family":"Fejes","sequence":"first","affiliation":[{"name":"Institute of Surgical Research, Albert Szent-Gy\u00f6rgyi Medical School, University of Szeged, 6720 Szeged, Hungary"},{"name":"Department of Internal Medicine, H\u00f3dmez\u0151v\u00e1s\u00e1rhely-Mak\u00f3 Healthcare Center, H-6900 K\u00f3rh\u00e1z Street 2, 6900 Mak\u00f3, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tam\u00e1s","family":"J\u00e1mbor","sequence":"additional","affiliation":[{"name":"Institute of Surgical Research, Albert Szent-Gy\u00f6rgyi Medical School, University of Szeged, 6720 Szeged, Hungary"},{"name":"Department of Internal Medicine, H\u00f3dmez\u0151v\u00e1s\u00e1rhely-Mak\u00f3 Healthcare Center, H-6900 K\u00f3rh\u00e1z Street 2, 6900 Mak\u00f3, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3139-0235","authenticated-orcid":false,"given":"Andrea","family":"Szab\u00f3","sequence":"additional","affiliation":[{"name":"Institute of Surgical Research, Albert Szent-Gy\u00f6rgyi Medical School, University of Szeged, 6720 Szeged, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Szabolcs P\u00e9ter","family":"Tall\u00f3sy","sequence":"additional","affiliation":[{"name":"Institute of Surgical Research, Albert Szent-Gy\u00f6rgyi Medical School, University of Szeged, 6720 Szeged, Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,3,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"529","DOI":"10.7150\/ijbs.33007","article-title":"Empagliflozin attenuates hyperuricemia by upregulation of ABCG2 via AMPK\/AKT\/CREB signaling pathway in type 2 diabetic mice","volume":"16","author":"Lu","year":"2020","journal-title":"Int. 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