{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T22:57:00Z","timestamp":1787871420057,"version":"build-2784847793"},"reference-count":64,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2024,12,24]],"date-time":"2024-12-24T00:00:00Z","timestamp":1734998400000},"content-version":"vor","delay-in-days":23,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Obesity Science &amp;amp; Practice"],"published-print":{"date-parts":[[2024,12]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Endogenous glucagon\u2010like peptide\u20101 (GLP\u20101) and glucose\u2010dependent insulinotropic polypeptide (GIP) regulate islet cell function. GLP\u20101 receptor agonists (GLP\u20101RAs) have been associated with an elevated risk of acute pancreatitis. Data on the pancreatic safety of tirzepatide (a dual GLP\u20101 and GIP agonist) and its effects on islet cell function in randomized controlled trials (RCTs) are scarce. Moreover, no meta\u2010analysis has comprehensively examined such effects of tirzepatide.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Electronic databases were searched for RCTs with tirzepatide as the intervention and a placebo or active comparator as the control. The primary outcome was adjudication\u2010confirmed pancreatitis; secondary outcomes were the percent changes from baseline in serum pancreatic amylase, lipase, insulin, C\u2010peptide, glucagon, and homeostasis model assessment of insulin resistance (HOMA2\u2010IR).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Seventeen RCTs with 18 published reports involving 14,645 subjects were analyzed. Over a follow\u2010up duration of 12\u201372\u00a0weeks, tirzepatide had identical risks of pancreatitis to placebo (tirzepatide 5\u00a0mg: RR 2.04, 95% CI [0.27\u201315.69],\n                      <jats:italic>p<\/jats:italic>\n                      \u00a0=\u00a00.49; 10\u00a0mg: RR 0.63, 95% CI [0.08\u20135.12],\n                      <jats:italic>p<\/jats:italic>\n                      \u00a0=\u00a00.67; and 15\u00a0mg: RR 1.26, 95% CI [0.36\u20134.98],\n                      <jats:italic>p<\/jats:italic>\n                      \u00a0=\u00a00.72). Tirzepatide was also associated with comparable risks of pancreatitis to insulin and GLP\u20101RAs. However, tirzepatide (at all doses) caused greater increases in pancreatic amylase and lipase than placebo and insulin. Individuals on tirzepatide 15\u00a0mg and GLP\u20101RAs had similar risks of having increased lipase levels. The percent reductions in fasting insulin were greater with tirzepatide 10 and 15\u00a0mg than with placebo. All doses of tirzepatide caused greater percent reductions in fasting insulin, C\u2010peptide, and glucagon than GLP\u20101RAs. Compared to placebo and GLP\u20101RAs, the percent reductions in HOMA2\u2010IR were greater with all doses of tirzepatide.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>The meta\u2010analysis provides evidence of the safety of tirzepatide regarding pancreatitis and establishes its positive effect on islet cell functions and insulin resistance.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/osp4.70032","type":"journal-article","created":{"date-parts":[[2024,12,24]],"date-time":"2024-12-24T09:23:21Z","timestamp":1735032201000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Pancreatic Safety of Tirzepatide and Its Effects on Islet Cell Function: A Systematic Review and Meta\u2010Analysis"],"prefix":"10.1002","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5681-6522","authenticated-orcid":false,"given":"A. B. M.","family":"Kamrul\u2010Hasan","sequence":"first","affiliation":[{"name":"Department of Endocrinology Mymensingh Medical College  Mymensingh Bangladesh"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3064-466X","authenticated-orcid":false,"given":"Sunetra","family":"Mondal","sequence":"additional","affiliation":[{"name":"Department of Endocrinology NRS Medical College  Kolkata India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4915-8805","authenticated-orcid":false,"given":"Deep","family":"Dutta","sequence":"additional","affiliation":[{"name":"Department of Endocrinology CEDAR Superspeciality Clinics  New Delhi India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6865-5554","authenticated-orcid":false,"given":"Lakshmi","family":"Nagendra","sequence":"additional","affiliation":[{"name":"Department of Endocrinology JSS Medical College JSS Academy of Higher Education &amp; Research  Mysore India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0468-349X","authenticated-orcid":false,"given":"Mohammed Ruhul","family":"Kabir","sequence":"additional","affiliation":[{"name":"Department of Medicine Sylhet MAG Osmani Medical College  Sylhet Bangladesh"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0886-5255","authenticated-orcid":false,"given":"Joseph M.","family":"Pappachan","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Metabolism Lancashire Teaching Hospitals NHS Trust &amp; Manchester Metropolitan University  Preston UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,12,24]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molmet.2018.09.009"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.2040\u20101124.2010.00022.x"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.2337\/db11\u20101109"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpgi.1998.275.5.G984"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.2337\/db09\u20100626"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.21037\/atm.2018.02.24"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2022.1043789"},{"key":"e_1_2_9_9_1","volume-title":"Advancing Health through Innovation","author":"New Drug Therapy Approvals","year":"2022"},{"key":"e_1_2_9_10_1","volume-title":"FDA Approves New Medication for Chronic Weight Management","author":"FDA News Release","year":"2024"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.dsx.2022.102640"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.17925\/EE.2024.20.2.10"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2023.1214334"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1210\/clinem\/dgaa863"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.3803\/EnM.2023.1839"},{"key":"e_1_2_9_16_1","volume-title":"Cochrane Handbook for Systematic Reviews of Interventions Version 6.4 (Updated August 2023)","author":"Higgins J. 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