{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,8]],"date-time":"2026-06-08T06:59:10Z","timestamp":1780901950577,"version":"3.54.1"},"reference-count":30,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2026,6,6]],"date-time":"2026-06-06T00:00:00Z","timestamp":1780704000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Objective: Insulin resistance is a key pathophysiological driver linking obesity and type 2 diabetes (T2D) with cardiovascular risk. Composite surrogate indices derived from routine clinical parameters, such as the Metabolic Score for Insulin Resistance (METS-IR) and the Single Point Insulin Sensitivity Estimator (SPISE), may provide a practical means of capturing multidimensional metabolic changes. Given that comparative data are limited, we aimed to evaluate the effects of sodium\u2013glucose cotransporter-2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP-1RA) on these indices in individuals with T2D and overweight or obesity. Methods: In this retrospective observational study, 100 individuals with T2D treated with either GLP-1RA (n = 54) or SGLT2i (n = 46) were evaluated over 6 months. Strict inclusion criteria ensured treatment stability without initiation or modification of concomitant pharmacotherapy. Changes in METS-IR and SPISE were assessed alongside body mass index (BMI) and glycated hemoglobin (HbA1c). Multivariable regression and exploratory analyses, including stratification by BMI and correlation analyses, were performed. Results: Both treatment groups demonstrated significant improvements in METS-IR (GLP-1RA: \u22123.9 \u00b1 5.9; SGLT2i: \u22122.5 \u00b1 2.6; both p &lt; 0.001) and SPISE (GLP-1RA: +0.46 \u00b1 0.52; SGLT2i: +0.44 \u00b1 0.61; both p &lt; 0.001), with no significant between-group differences. In the GLP-1RA group, changes in METS-IR correlated with changes in BMI (r = 0.48, p &lt; 0.001) and HbA1c (r = 0.29, p = 0.030), whereas no significant correlations were observed in the SGLT2i group. Stratified analyses indicated greater reductions in METS-IR among individuals with BMI \u226530 kg\/m2 treated with GLP-1RA. Conclusions: Both SGLT2i and GLP-1RA improve composite surrogate markers of insulin resistance, with distinct associations with weight and glycemic changes. METS-IR and SPISE may serve as practical tools for monitoring multidimensional metabolic responses in clinical practice.<\/jats:p>","DOI":"10.3390\/jcm15124403","type":"journal-article","created":{"date-parts":[[2026,6,8]],"date-time":"2026-06-08T05:43:46Z","timestamp":1780897426000},"page":"4403","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Comparative Effects of SGLT2 Inhibitors and GLP-1 Receptor Agonists on Composite Surrogate Markers of Insulin Resistance: A Real-World Study Using METS-IR and SPISE"],"prefix":"10.3390","volume":"15","author":[{"given":"Dimitra","family":"Voziki","sequence":"first","affiliation":[{"name":"Department of Internal Medicine and Diabetes Clinic, \u201cG. Gennimatas\u201d General Hospital, 54635 Thessaloniki, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ioannis","family":"Stergiou","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine and Diabetes Clinic, \u201cG. Gennimatas\u201d General Hospital, 54635 Thessaloniki, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ioanna","family":"Zografou","sequence":"additional","affiliation":[{"name":"Second Propaedeutic Department of Internal Medicine, Medical School, Hippokration General Hospital, Aristotle University of Thessaloniki, 54642 Thessaloniki, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Mavridou","sequence":"additional","affiliation":[{"name":"Second Propaedeutic Department of Internal Medicine, Medical School, Hippokration General Hospital, Aristotle University of Thessaloniki, 54642 Thessaloniki, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2146-1194","authenticated-orcid":false,"given":"Lefteris","family":"Teperikidis","sequence":"additional","affiliation":[{"name":"Clinical Research Unit, Special Unit for Biomedical Research and Education (SUBRE), School of Medicine, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Doumas","sequence":"additional","affiliation":[{"name":"Second Propaedeutic Department of Internal Medicine, Medical School, Hippokration General Hospital, Aristotle University of Thessaloniki, 54642 Thessaloniki, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7162-3323","authenticated-orcid":false,"given":"Evangelos N.","family":"Liberopoulos","sequence":"additional","affiliation":[{"name":"First Department of Propaedeutic Internal Medicine, Medical School, National and Kapodistrian University of Athens, Laiko General Hospital, 11527 Athens, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2376-740X","authenticated-orcid":false,"given":"Kalliopi","family":"Kotsa","sequence":"additional","affiliation":[{"name":"Division of Endocrinology and Metabolism and Diabetes Center, First Department of Internal Medicine, Medical School, Aristotle University of Thessaloniki, AHEPA University Hospital, 54636 Thessaloniki, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matilda","family":"Florentin","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, School of Health Sciences, University of Ioannina, 45110 Ioannina, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5853-1352","authenticated-orcid":false,"given":"Theocharis","family":"Koufakis","sequence":"additional","affiliation":[{"name":"Second Propaedeutic Department of Internal Medicine, Medical School, Hippokration General Hospital, Aristotle University of Thessaloniki, 54642 Thessaloniki, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,6,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"436","DOI":"10.31083\/j.rcm2512436","article-title":"Diabetes Mellitus and Cardiovascular Disease: Exploring Epidemiology, Pathophysiology, and Treatment Strategies","volume":"25","author":"Siam","year":"2024","journal-title":"Rev. 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