{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,3]],"date-time":"2026-11-03T09:08:29Z","timestamp":1793696909101,"version":"4.5.1"},"reference-count":62,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2025,9,3]],"date-time":"2025-09-03T00:00:00Z","timestamp":1756857600000},"content-version":"vor","delay-in-days":2,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100008091","name":"Golestan University of Medical Sciences","doi-asserted-by":"publisher","award":["112852"],"award-info":[{"award-number":["112852"]}],"id":[{"id":"10.13039\/501100008091","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Endocrino Diabet &amp;amp; Metabol"],"published-print":{"date-parts":[[2025,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Chronic inflammation is a critical factor contributing to diabetes complications. Baricitinib inhibits JAK\u2013STAT signalling, which can contribute to an anti\u2010inflammatory effect. Similarly, metformin demonstrates anti\u2010inflammatory properties by activating the AMPK\u2013SIRT pathway and suppressing the NF\u2010\u1d0bB signalling pathway. Here, we explored the effects of the coadministration of metformin and baricitinib in diabetic rats.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Streptozotocin (40\u2009mg\/kg body weight) was administered to rats to develop diabetes after 2\u2009weeks of 10% fructose solution consumption. The rats were treated with baricitinib (0.5, 2.5 and 5\u2009mg\/kg) and 150\u2009mg\/kg metformin for 1 month. A dose of 0.5\u2009mg\/kg baricitinib was chosen for combination therapy with metformin.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Key Findings<\/jats:title>\n                    <jats:p>\n                      Baricitinib induced significant weight loss at all three doses (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009\u2264\u20090.05) and significantly increased lipid profile parameters in comparison to the diabetic control group (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009\u2264\u20090.05). Pancreatic NF\u2010\u1d0bB levels and HOMA\u2010IR were meaningfully reduced in all treatment groups (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009\u2264\u20090.01). Metformin and combination therapy significantly reduced serum TNF\u2010\u03b1 levels (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009\u2264\u20090.05). Furthermore, baricitinib at different doses and combination therapy significantly elevated serum IL\u201010 levels (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009\u2264\u20090.05). Additionally, combination therapy significantly upregulated the liver expression of NF\u2010\u1d0bB, SOCS1, SOCS3, AMPK and SIRT\u20101 (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009\u2264\u20090.01).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Our results suggest that the coadministration of metformin with baricitinib reduces insulin resistance, improves histopathological alterations in the liver and pancreatic islet cells and counteracts the adverse effects of baricitinib on the lipid profile in diabetic rats. These findings hold particular significance for patients undergoing baricitinib treatment.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/edm2.70101","type":"journal-article","created":{"date-parts":[[2025,9,4]],"date-time":"2025-09-04T05:34:32Z","timestamp":1756964072000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Combined Metformin and Baricitinib Therapy Attenuates Inflammation in\n                    <scp>STZ<\/scp>\n                    \u2010Induced Diabetic Rats via\n                    <scp>AMPK<\/scp>\n                    \/\n                    <scp>JAK<\/scp>\n                    \u2013\n                    <scp>STAT<\/scp>\n                    Pathway Crosstalk"],"prefix":"10.1002","volume":"8","author":[{"given":"Mostafa","family":"Allahyari","sequence":"first","affiliation":[{"name":"Metabolic Disorders Research Center Golestan University of Medical Sciences  Gorgan 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