{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T20:54:45Z","timestamp":1790456085373,"version":"4.1.0"},"reference-count":57,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2024,4,1]],"date-time":"2024-04-01T00:00:00Z","timestamp":1711929600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["dom-pubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Diabetes Obesity Metabolism"],"published-print":{"date-parts":[[2024,7]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>To evaluate the efficacy and cardiovascular outcomes of combination pioglitazone with either a glucagon\u2010like peptide\u20101 receptor agonist (GLP\u20101RA) or a sodium\u2010glucose cotransporter\u20102 (SGLT2) inhibitor in individuals with type 2 diabetes (T2D) by conducting a systematic review, meta\u2010analysis, and analysis of a large international real\u2010world database.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We searched MEDLINE, SCOPUS and Web of Science to identify relevant articles for inclusion (PROSPERO [CRD: 42023483126]). Nineteen studies assessing pioglitazone\u2009+\u2009SGLT2 inhibitors or GLP\u20101RAs versus controls were identified, 16 of which were randomized controlled trials. Risk of bias was assessed using Cochrane\u2010endorsed tools and quality of evidence was assessed using GRADE. We additionally performed a retrospective cohort study of all individuals aged 18\u2009years or over with T2D, using the TriNetX platform. We included propensity\u2010score\u2010matched individuals who were treated for at least 1\u2009year with pioglitazone and a GLP\u20101RA or pioglitazone and an SGLT2 inhibitor, compared against GLP\u20101RA and SGLT2 inhibitor monotherapy. Outcomes were all\u2010cause mortality, heart failure, chronic kidney disease and composite stroke and transient ischaemic attack.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The average follow\u2010up in the included studies ranged from 24 to 52\u2009weeks. Combination of pioglitazone with a GLP\u20101RA reduced glycated haemoglobin (HbA1c) and weight greater than in controls: mean differences \u22121% (95% confidence interval [CI] \u22121.27, \u22120.74) and \u22121.19\u2009kg (95% CI \u22121.80, \u22120.58), respectively. There was no statistically significant difference in systolic blood pressure (SBP) or mortality between groups: mean difference\u2009\u2212\u20091.56\u2009mmHg (95% CI \u22124.48, 1.35;\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.30) and relative risk (RR) 0.29 (95% CI 0.07\u20131.15;\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.08), respectively. Combination of pioglitazone with SGLT2 inhibitors reduced HbA1c, weight and SBP to a greater extent than control treatment: mean differences \u22120.48% (95% CI \u22120.67, \u22120.28), \u22122.3\u2009kg (95% CI \u22122.72, \u22121.88) and \u22122.4\u2009mmHg (95% CI \u22124.1, \u22120.7;\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.01), respectively. There was no statistically significant difference in mortality between groups (RR 1.81, 95% CI 0.30\u201310.97;\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.52). The included trials demonstrated a reduction in risk of heart failure with combination treatment. Similarly, from the real\u2010world database (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u200925\u2009230 identified), pioglitazone and SGLT2 inhibitor combination therapy was associated with reduced risk of heart failure compared to monotherapy alone (hazard ratio 0.50, 95% CI 0.38\u20130.65;\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Both our systematic review\/meta\u2010analysis and the real\u2010world dataset show that combination of pioglitazone with either GLP\u20101RAs or SGLT2 inhibitors is associated with increased weight loss and reduced risk of heart failure compared with monotherapy.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/dom.15576","type":"journal-article","created":{"date-parts":[[2024,4,1]],"date-time":"2024-04-01T06:19:35Z","timestamp":1711952375000},"page":"2606-2623","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Effect of combination pioglitazone with sodium\u2010glucose cotransporter\u20102 inhibitors or\n                    <scp>glucagon\u2010like peptide<\/scp>\n                    \u20101\n                    <scp>receptor agonists<\/scp>\n                    on outcomes in type 2 diabetes: A systematic review, meta\u2010analysis, and real\u2010world study from an international federated database"],"prefix":"10.1111","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9991-7369","authenticated-orcid":false,"given":"Matthew","family":"Anson","sequence":"first","affiliation":[{"name":"Diabetes &amp; Endocrinology Research and Pain Research Institute, Institute of Life Course and Medical Sciences University of Liverpool and Liverpool University Hospital NHS Foundation Trust  Liverpool UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alex E.","family":"Henney","sequence":"additional","affiliation":[{"name":"Diabetes &amp; Endocrinology Research and Pain Research Institute, Institute of Life Course and Medical Sciences University of Liverpool and Liverpool University Hospital NHS Foundation Trust  Liverpool UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sizheng S.","family":"Zhao","sequence":"additional","affiliation":[{"name":"Centre for Musculoskeletal Research, Division of Musculoskeletal and Dermatological Science, School of Biological Sciences, Faculty of Biological Medicine and Health, The University of Manchester Manchester Academic Health Science Centre  Manchester UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gema H.","family":"Ibarburu","sequence":"additional","affiliation":[{"name":"TriNetX LLC  Cambridge Massachusetts USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7566-1626","authenticated-orcid":false,"given":"Gregory Y. 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