{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T03:14:29Z","timestamp":1793330069274,"version":"4.5.0"},"reference-count":75,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,9,19]],"date-time":"2025-09-19T00:00:00Z","timestamp":1758240000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>This study aims to evaluate and compare the gastrointestinal adverse effects associated with different GLP-1 receptor agonists (GLP-1RAs) and multi-target analogs in patients with type 2 diabetes mellitus (T2DM) using a Bayesian network meta-analysis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      A systematic search of PubMed, Embase, Cochrane Library, and\n                      <jats:ext-link>ClinicalTrials.gov<\/jats:ext-link>\n                      was conducted to identify randomized controlled trials (RCTs) assessing the gastrointestinal adverse events of GLP-1RAs in T2DM patients. Inclusion criteria included adult patients with confirmed T2DM receiving any GLP-1RA, with the outcomes focused on gastrointestinal adverse events such as nausea, vomiting, diarrhea, constipation, dyspepsia, and reduced appetite. Bayesian network meta-analysis was used to calculate the odds ratios (ORs) and 95% confidence intervals (CIs) for the comparison of gastrointestinal side effects among different GLP-1RAs.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>A total of 48 RCTs involving 27,729 participants were included in the analysis. The overall incidence of gastrointestinal adverse events was 11.66%, with nausea being the most frequent (21.49%) and reduced appetite the least frequent (5.49%). Tirzepatide had the highest risk of inducing nausea and diarrhea, while dulaglutide and lixisenatide had the lowest risks. Exenatide exhibited the highest incidence of vomiting, while dulaglutide showed a lower risk. Semaglutide demonstrated a significantly higher risk of diarrhea compared to other GLP-1RAs.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>This study highlights significant differences in the gastrointestinal adverse event profiles of various GLP-1RAs. Tirzepatide exhibited the highest risk of gastrointestinal side effects, whereas dulaglutide and exenatide showed relatively better tolerability. These findings provide valuable insights for clinicians to make informed treatment decisions, emphasizing the importance of individualized therapy based on patient tolerance.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Systematic Review Registration<\/jats:title>\n                    <jats:p>CRD42024592308.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fphar.2025.1613610","type":"journal-article","created":{"date-parts":[[2025,9,19]],"date-time":"2025-09-19T08:28:24Z","timestamp":1758270504000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":53,"title":["Comparative gastrointestinal adverse effects of GLP-1 receptor agonists and multi-target analogs in type 2 diabetes: a Bayesian network meta-analysis"],"prefix":"10.3389","volume":"16","author":[{"given":"Xingmiao","family":"Xie","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuiyuan","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuzhen","family":"Deng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuying","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhibin","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Binghong","family":"He","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,9,19]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1803","DOI":"10.1016\/s0140-6736(22)01655-5","article-title":"Type 2 diabetes","volume":"400","author":"Ahmad","year":"2022","journal-title":"Lancet London, England"},{"key":"B2","doi-asserted-by":"publisher","first-page":"1056","DOI":"10.1111\/dom.12539","article-title":"Efficacy and safety of liraglutide versus placebo added to basal insulin analogues (with or without metformin) in patients with type 2 diabetes: a randomized, placebo-controlled trial","volume":"17","author":"Ahmann","year":"2015","journal-title":"Diabetes, Obes. and metabolism"},{"key":"B3","doi-asserted-by":"publisher","first-page":"258","DOI":"10.2337\/dc17-0417","article-title":"Efficacy and safety of once-weekly semaglutide versus exenatide Er in Subjects with type 2 diabetes (Sustain 3): a 56-Week, Open-Label, randomized clinical trial","volume":"41","author":"Ahmann","year":"2018","journal-title":"Diabetes care"},{"key":"B4","doi-asserted-by":"publisher","first-page":"2543","DOI":"10.2337\/dc12-2006","article-title":"Efficacy and safety of lixisenatide once-daily Morning or evening Injections in type 2 diabetes Inadequately controlled on Metformin (Getgoal-M)","volume":"36","author":"Ahr\u00e9n","year":"2013","journal-title":"Diabetes care"},{"key":"B5","doi-asserted-by":"publisher","first-page":"341","DOI":"10.1016\/s2213-8587(17)30092-x","article-title":"Efficacy and safety of once-weekly semaglutide versus once-daily Sitagliptin as an add-on to metformin, thiazolidinediones, or both, in patients with type 2 diabetes (sustain 2): a 56-week, double-blind, phase 3a, randomised trial","volume":"5","author":"Ahr\u00e9n","year":"2017","journal-title":"lancet Diabetes and Endocrinol."},{"key":"B6","doi-asserted-by":"publisher","first-page":"468.e9","DOI":"10.1016\/j.amjmed.2009.11.019","article-title":"Effects of exenatide combined with lifestyle modification in patients with type 2 diabetes","volume":"123","author":"Apovian","year":"2010","journal-title":"Am. J. Med."},{"key":"B7","doi-asserted-by":"publisher","first-page":"R1011","DOI":"10.1152\/ajpregu.00424.2010","article-title":"Brain activation following peripheral administration of the glp-1 receptor agonist Exendin-4","volume":"301","author":"Baraboi","year":"2011","journal-title":"Am. J. physiology Regul. Integr. Comp. physiology"},{"key":"B8","doi-asserted-by":"publisher","first-page":"1242","DOI":"10.1111\/dom.12932","article-title":"Effects of once-weekly semaglutide on appetite, Energy intake, control of eating, food preference and body weight in subjects with obesity","volume":"19","author":"Blundell","year":"2017","journal-title":"Diabetes, Obes. and metabolism"},{"key":"B9","doi-asserted-by":"publisher","first-page":"176","DOI":"10.1111\/dme.12328","article-title":"Efficacy and safety of lixisenatide once daily vs. Placebo in People with type 2 diabetes insufficiently controlled on metformin (getgoal-F1)","volume":"31","author":"Bolli","year":"2014","journal-title":"Diabet. Med. a J. Br. Diabet. Assoc."},{"key":"B10","doi-asserted-by":"publisher","first-page":"2545","DOI":"10.2337\/db21-0459","article-title":"Gip receptor agonism attenuates glp-1 receptor agonist-induced nausea and emesis in preclinical models","volume":"70","author":"Borner","year":"2021","journal-title":"Diabetes"},{"key":"B11","doi-asserted-by":"publisher","first-page":"434","DOI":"10.1080\/10618600.1998.10474787","article-title":"General methods for monitoring convergence of iterative simulations","volume":"7","author":"Brooks","year":"1998","journal-title":"J. Comput. Graph. statistics"},{"key":"B12","doi-asserted-by":"publisher","first-page":"2628","DOI":"10.2337\/diacare.27.11.2628","article-title":"Effects of exenatide (Exendin-4) on glycemic control over 30 Weeks in sulfonylurea-treated patients with type 2 diabetes","volume":"27","author":"Buse","year":"2004","journal-title":"Diabetes care"},{"key":"B13","doi-asserted-by":"publisher","first-page":"39","DOI":"10.1016\/s0140-6736(09)60659-0","article-title":"Liraglutide once a day versus exenatide twice a day for type 2 diabetes: a 26-week randomised, parallel-group, multinational, open-label trial (Lead-6)","volume":"374","author":"Buse","year":"2009","journal-title":"Lancet London, England"},{"key":"B14","doi-asserted-by":"publisher","first-page":"103","DOI":"10.7326\/0003-4819-154-2-201101180-00300","article-title":"Use of twice-daily exenatide in basal insulin-treated patients with type 2 diabetes: a randomized, controlled trial","volume":"154","author":"Buse","year":"2011","journal-title":"Ann. Intern. Med."},{"key":"B15","doi-asserted-by":"publisher","first-page":"117","DOI":"10.1016\/s0140-6736(12)61267-7","article-title":"Exenatide once weekly versus liraglutide once daily in patients with type 2 diabetes (Duration-6): a randomised, open-label study","volume":"381","author":"Buse","year":"2013","journal-title":"Lancet London, England"},{"key":"B16","doi-asserted-by":"publisher","first-page":"100","DOI":"10.1016\/j.diabet.2019.101117","article-title":"Efficacy and safety of once-weekly semaglutide 1.0mg vs once-daily liraglutide 1.2mg as add-on to 1-3 oral antidiabetic drugs in subjects with type 2 diabetes (sustain 10)","volume":"46","author":"Capehorn","year":"2020","journal-title":"Diabetes and metabolism"},{"key":"B17","doi-asserted-by":"publisher","first-page":"1460","DOI":"10.1001\/jama.2017.14752","article-title":"Effect of oral semaglutide compared with placebo and subcutaneous semaglutide on glycemic control in patients with type 2 diabetes: a randomized clinical trial","volume":"318","author":"Davies","year":"2017","journal-title":"Jama"},{"key":"B18","doi-asserted-by":"publisher","first-page":"1092","DOI":"10.2337\/diacare.28.5.1092","article-title":"Effects of exenatide (Exendin-4) on glycemic control and weight over 30 Weeks in metformin-treated patients with type 2 diabetes","volume":"28","author":"DeFronzo","year":"2005","journal-title":"Diabetes care"},{"key":"B19","doi-asserted-by":"publisher","first-page":"1349","DOI":"10.1016\/s0140-6736(14)60976-4","article-title":"Once-weekly dulaglutide versus once-daily liraglutide in metformin-treated patients with type 2 diabetes (Award-6): a randomised, open-label, phase 3, non-inferiority trial","volume":"384","author":"Dungan","year":"2014","journal-title":"Lancet London, England"},{"key":"B20","doi-asserted-by":"publisher","first-page":"475","DOI":"10.1111\/dom.12634","article-title":"A 24-week study to evaluate the efficacy and safety of once-weekly dulaglutide added on to glimepiride in type 2 diabetes (Award-8)","volume":"18","author":"Dungan","year":"2016","journal-title":"Diabetes, Obes. and metabolism"},{"key":"B21","doi-asserted-by":"publisher","first-page":"731","DOI":"10.1161\/hypertensionaha.114.03062","article-title":"Effects of the once-weekly glucagon-like peptide-1 receptor agonist dulaglutide on ambulatory blood pressure and heart rate in patients with type 2 diabetes mellitus","volume":"64","author":"Ferdinand","year":"2014","journal-title":"Hypertens. (Dallas, Tex 1979)"},{"key":"B22","doi-asserted-by":"publisher","first-page":"503","DOI":"10.1056\/NEJMoa2107519","article-title":"Tirzepatide versus semaglutide once weekly in patients with type 2 diabetes","volume":"385","author":"Fr\u00edas","year":"2021","journal-title":"N. Engl. J. Med."},{"key":"B23","doi-asserted-by":"publisher","first-page":"2375","DOI":"10.1111\/dom.14163","article-title":"Efficacy and safety of polyethylene glycol loxenatide as add-on to metformin in patients with type 2 diabetes: a multicentre, randomized, double-blind, placebo-controlled, phase 3b trial","volume":"22","author":"Gao","year":"2020","journal-title":"Diabetes, Obes. and metabolism"},{"key":"B24","doi-asserted-by":"publisher","first-page":"339","DOI":"10.1177\/096228029600500402","article-title":"Markov chain Monte Carlo methods in biostatistics","volume":"5","author":"Gelman","year":"1996","journal-title":"Stat. methods Med. Res."},{"key":"B25","doi-asserted-by":"publisher","first-page":"e1263","DOI":"10.1097\/cce.0000000000001263","article-title":"Impact of glucagon-like peptide-1 receptor agonist exposure on gastrointestinal outcomes among icu patients: a multicenter matched cohort study","volume":"7","author":"Gmehlin","year":"2025","journal-title":"Crit. care Explor."},{"key":"B26","doi-asserted-by":"publisher","first-page":"E15743624346660","DOI":"10.2174\/0115743624346660250317013032","article-title":"Utilizing semaglutide for addressing type-2 diabetes and obesity","volume":"20","author":"Gupta","year":"2025","journal-title":"Curr. Signal Transduct. Ther."},{"key":"B27","doi-asserted-by":"publisher","first-page":"1509947","DOI":"10.3389\/fmed.2025.1509947","article-title":"Gastrointestinal adverse events associated with glp-1 receptor agonists in metabolic dysfunction-associated steatotic liver disease (masld): a systematic review and meta-analysis","volume":"12","author":"Huang","year":"2025","journal-title":"Front. Med."},{"key":"B28","doi-asserted-by":"publisher","first-page":"e81891","DOI":"10.7759\/cureus.81891","article-title":"Glp-1 receptor agonists in diabetes and obesity: a case report and review of bowel obstruction risks and management","volume":"17","author":"Jones","year":"2025","journal-title":"Cureus"},{"key":"B29","doi-asserted-by":"publisher","first-page":"1602","DOI":"10.1038\/s41467-018-03941-2","article-title":"Targeting glp-1 receptor trafficking to improve agonist efficacy","volume":"9","author":"Jones","year":"2018","journal-title":"Nat. Commun."},{"key":"B30","doi-asserted-by":"publisher","first-page":"591","DOI":"10.1016\/j.giec.2024.06.006","article-title":"Weight loss pharmacotherapy: current and future therapies","volume":"34","author":"Jordan","year":"2024","journal-title":"Gastrointest. Endosc. Clin. N. Am."},{"key":"B31","doi-asserted-by":"publisher","first-page":"210","DOI":"10.1111\/j.2040-1124.2010.00084.x","article-title":"Improved glycemic control and reduced bodyweight with exenatide: a double-blind, randomized, phase 3 study in Japanese patients with suboptimally controlled type 2 diabetes over 24 weeks","volume":"2","author":"Kadowaki","year":"2011","journal-title":"J. diabetes investigation"},{"key":"B32","doi-asserted-by":"publisher","first-page":"3122","DOI":"10.3390\/jcm14093122","article-title":"Glucagon-like peptide-1 receptor agonists in the context of eating disorders: a promising therapeutic option or a double-edged sword?","volume":"14","author":"Ka\u0142as","year":"2025","journal-title":"J. Clin. Med."},{"key":"B33","doi-asserted-by":"publisher","first-page":"1206","DOI":"10.1007\/s00125-024-06144-1","article-title":"Subcutaneously administered tirzepatide vs semaglutide for adults with type 2 diabetes: a systematic review and network meta-analysis of randomised controlled trials","volume":"67","author":"Karagiannis","year":"2024","journal-title":"Diabetologia"},{"key":"B34","doi-asserted-by":"publisher","first-page":"1083","DOI":"10.2337\/diacare.28.5.1083","article-title":"Effects of exenatide (Exendin-4) on glycemic control over 30 Weeks in patients with type 2 diabetes treated with metformin and a sulfonylurea","volume":"28","author":"Kendall","year":"2005","journal-title":"Diabetes care"},{"key":"B35","doi-asserted-by":"publisher","first-page":"3490","DOI":"10.1111\/dom.16376","article-title":"Adverse drug reaction patterns of glp-1 receptor agonists approved for obesity treatment: disproportionality analysis from global pharmacovigilance database","volume":"27","author":"Kim","year":"2025","journal-title":"Diabetes, Obes. and metabolism"},{"key":"B36","doi-asserted-by":"publisher","first-page":"5474","DOI":"10.1111\/dom.15875","article-title":"A long-acting glucose-dependent insulinotropic polypeptide receptor agonist improves the gastrointestinal tolerability of glucagon-like peptide-1 receptor agonist therapy","volume":"26","author":"Knop","year":"2024","journal-title":"Diabetes, Obes. and metabolism"},{"key":"B37","doi-asserted-by":"publisher","first-page":"577","DOI":"10.1007\/s001250050949","article-title":"The effect of single doses of pramlintide on gastric emptying of two meals in men with iddm","volume":"41","author":"Kong","year":"1998","journal-title":"Diabetologia"},{"key":"B38","doi-asserted-by":"publisher","first-page":"2565","DOI":"10.1111\/dom.13422","article-title":"Effect of once-weekly semaglutide on the counterregulatory response to hypoglycaemia in People with type 2 diabetes: a randomized, placebo-controlled, double-blind, crossover trial","volume":"20","author":"Korsatko","year":"2018","journal-title":"Diabetes, Obes. and metabolism"},{"key":"B39","doi-asserted-by":"publisher","first-page":"123","DOI":"10.2147\/dmso.S130834","article-title":"Glucagon-like peptide-1 receptor agonists: a systematic review of comparative effectiveness research","volume":"10","author":"Levin","year":"2017","journal-title":"Diabetes, metabolic syndrome Obes. targets Ther."},{"key":"B40","doi-asserted-by":"publisher","first-page":"h5364","DOI":"10.1136\/bmj.h5364","article-title":"Liraglutide in People treated for type 2 diabetes with multiple daily insulin injections: randomised clinical trial (mdi liraglutide trial)","volume":"351","author":"Lind","year":"2015","journal-title":"BMJ Clin. Res. ed"},{"key":"B41","doi-asserted-by":"publisher","first-page":"1926","DOI":"10.2337\/dc17-2381","article-title":"A 26-week randomized controlled trial of semaglutide once daily versus liraglutide and placebo in patients with type 2 diabetes suboptimally controlled on diet and exercise with or without metformin","volume":"41","author":"Lingvay","year":"2018","journal-title":"Diabetes care"},{"key":"B42","doi-asserted-by":"publisher","first-page":"668","DOI":"10.3390\/ph18050668","article-title":"The efficacy and safety of tirzepatide in patients with diabetes and\/or obesity: systematic review and meta-analysis of randomized clinical trials","volume":"18","author":"Liu","year":"2025","journal-title":"Pharmaceuticals"},{"key":"B43","doi-asserted-by":"publisher","first-page":"1058","DOI":"10.1111\/j.1463-1326.2010.01251.x","article-title":"A placebo\u2010controlled trial of exenatide twice\u2010daily added to thiazolidinediones alone or in combination with metformin","volume":"12","author":"Liutkus","year":"2010","journal-title":"Diabetes, Obes. metab."},{"key":"B44","doi-asserted-by":"publisher","first-page":"e20","DOI":"10.1192\/j.eurpsy.2024.1803","article-title":"Neuropsychiatric adverse events associated with glucagon-like peptide-1 receptor agonists: a pharmacovigilance analysis of the fda adverse event reporting system database","volume":"68","author":"Lu","year":"2025","journal-title":"Eur. psychiatry J. Assoc. Eur. Psychiatrists"},{"key":"B45","doi-asserted-by":"publisher","first-page":"370","DOI":"10.1016\/s2213-8587(18)30023-8","article-title":"Dulaglutide as add-on therapy to Sglt2 inhibitors in patients with inadequately controlled type 2 diabetes (Award-10): a 24-week, randomised, double-blind, placebo-controlled trial","volume":"6","author":"Ludvik","year":"2018","journal-title":"lancet Diabetes and Endocrinol."},{"key":"B46","doi-asserted-by":"publisher","first-page":"143","DOI":"10.1007\/s13300-020-00981-0","article-title":"The role of tirzepatide, dual gip and glp-1 receptor agonist, in the management of type 2 diabetes: the surpass clinical trials","volume":"12","author":"Min","year":"2021","journal-title":"Diabetes Ther. Res. Treat. Educ. diabetes Relat. Disord."},{"key":"B47","doi-asserted-by":"publisher","first-page":"549","DOI":"10.1016\/s2213-8587(19)30157-3","article-title":"Adjunctive liraglutide treatment in patients with persistent or recurrent type 2 diabetes after metabolic surgery (gravitas): a randomised, double-blind, placebo-controlled trial","volume":"7","author":"Miras","year":"2019","journal-title":"lancet Diabetes and Endocrinol."},{"key":"B48","doi-asserted-by":"publisher","first-page":"974","DOI":"10.1111\/dom.12534","article-title":"Once\u2010weekly glucagon\u2010like peptide\u20101 receptor agonist dulaglutide is non\u2010inferior to once\u2010daily liraglutide and superior to placebo in J apanese patients with type 2 diabetes: a 26\u2010week randomized phase iii study","volume":"17","author":"Miyagawa","year":"2015","journal-title":"Diabetes, Obes. Metab."},{"key":"B49","doi-asserted-by":"publisher","first-page":"515","DOI":"10.1016\/s2213-8587(19)30192-5","article-title":"Efficacy and safety of oral semaglutide in patients with type 2 diabetes and moderate renal impairment (pioneer 5): a placebo-controlled, randomised, phase 3a trial","volume":"7","author":"Mosenzon","year":"2019","journal-title":"lancet Diabetes and Endocrinol."},{"key":"B50","doi-asserted-by":"publisher","first-page":"e77089","DOI":"10.7759\/cureus.77089","article-title":"Efficacy and safety of efpeglenatide in patients with type 2 diabetes and obesity: a systematic review","volume":"17","author":"Narayan","year":"2025","journal-title":"Cureus"},{"key":"B51","doi-asserted-by":"publisher","first-page":"2149","DOI":"10.2337\/dc13-2761","article-title":"Efficacy and safety of dulaglutide versus sitagliptin after 52 Weeks in type 2 diabetes in a randomized controlled trial (Award-5)","volume":"37","author":"Nauck","year":"2014","journal-title":"Diabetes care"},{"key":"B52","doi-asserted-by":"publisher","first-page":"3780","DOI":"10.1111\/dom.16405","article-title":"Glp\u20101 medication and weight loss: barriers and motivators among 1659 participants managed in a virtual setting","volume":"27","author":"Naveed","year":"2025","journal-title":"Diabetes, Obes. Metab."},{"key":"B53","doi-asserted-by":"publisher","first-page":"1663","DOI":"10.1016\/j.jacc.2024.08.038","article-title":"Six substudies from the semaglutide trials: identifying mechanisms of benefit and whom to treat","volume":"84","author":"Pagidipati","year":"2024","journal-title":"J. Am. Coll. Cardiol."},{"key":"B54","doi-asserted-by":"publisher","first-page":"1000","DOI":"10.1111\/dom.12121","article-title":"Efficacy and safety of lixisenatide once daily versus placebo in type 2 diabetes insufficiently controlled on pioglitazone (getgoal-P)","volume":"15","author":"Pinget","year":"2013","journal-title":"Diabetes, Obes. and metabolism"},{"key":"B55","doi-asserted-by":"publisher","first-page":"1024","DOI":"10.1111\/dom.12937","article-title":"Placebo-controlled, randomized trial of the addition of once-weekly glucagon-like peptide-1 receptor agonist dulaglutide to titrated daily insulin glargine in patients with type 2 diabetes (Award-9)","volume":"19","author":"Pozzilli","year":"2017","journal-title":"Diabetes, Obes. and metabolism"},{"key":"B56","doi-asserted-by":"publisher","first-page":"275","DOI":"10.1016\/s2213-8587(18)30024-x","article-title":"Semaglutide versus dulaglutide once weekly in patients with type 2 diabetes (sustain 7): a randomised, open-label, phase 3b trial","volume":"6","author":"Pratley","year":"2018","journal-title":"lancet Diabetes and Endocrinol."},{"key":"B57","doi-asserted-by":"publisher","first-page":"39","DOI":"10.1016\/s0140-6736(19)31271-1","article-title":"Oral semaglutide versus subcutaneous liraglutide and placebo in type 2 diabetes (pioneer 4): a randomised, double-blind, phase 3a trial","volume":"394","author":"Pratley","year":"2019","journal-title":"Lancet London, England"},{"key":"B58","doi-asserted-by":"publisher","first-page":"2291","DOI":"10.1210\/jc.2018-00070","article-title":"Semaglutide added to basal insulin in type 2 diabetes (sustain 5): a randomized, controlled trial","volume":"103","author":"Rodbard","year":"2018","journal-title":"J. Clin. Endocrinol. metabolism"},{"key":"B59","doi-asserted-by":"publisher","first-page":"e2457349","DOI":"10.1001\/jamanetworkopen.2024.57349","article-title":"Discontinuation and reinitiation of dual-labeled glp-1 receptor agonists among us adults with overweight or obesity","volume":"8","author":"Rodriguez","year":"2025","journal-title":"JAMA Netw. open"},{"key":"B60","doi-asserted-by":"publisher","first-page":"2945","DOI":"10.2337\/dc12-2709","article-title":"Efficacy and safety of lixisenatide once daily versus exenatide twice daily in type 2 diabetes inadequately controlled on metformin: a 24-week, randomized, open-label, active-controlled study (Getgoal-X)","volume":"36","author":"Rosenstock","year":"2013","journal-title":"Diabetes care"},{"key":"B61","doi-asserted-by":"publisher","first-page":"386","DOI":"10.1016\/j.jdiacomp.2014.01.012","article-title":"Beneficial effects of once-daily lixisenatide on overall and postprandial glycemic levels without significant excess of hypoglycemia in type 2 diabetes inadequately controlled on a sulfonylurea with or without metformin (getgoal-S)","volume":"28","author":"Rosenstock","year":"2014","journal-title":"J. diabetes its Complicat."},{"key":"B62","doi-asserted-by":"publisher","first-page":"2046","DOI":"10.1007\/s00125-009-1472-y","article-title":"Liraglutide vs insulin glargine and placebo in combination with metformin and sulfonylurea therapy in type 2 diabetes mellitus (Lead-5 Met+Su): a randomised controlled trial","volume":"52","author":"Russell-Jones","year":"2009","journal-title":"Diabetologia"},{"key":"B63","doi-asserted-by":"publisher","first-page":"910","DOI":"10.1111\/j.1463-1326.2012.01618.x","article-title":"Randomized, double-blind, placebo-controlled trial of the once-daily glp-1 receptor agonist lixisenatide in asian patients with type 2 diabetes insufficiently controlled on basal insulin with or without a sulfonylurea (Getgoal-L-Asia)","volume":"14","author":"Seino","year":"2012","journal-title":"Diabetes, Obes. and metabolism"},{"key":"B64","doi-asserted-by":"publisher","first-page":"575","DOI":"10.1161\/circulationaha.121.055459","article-title":"Effect of the glucagon-like peptide-1 receptor agonists semaglutide and liraglutide on kidney outcomes in patients with type 2 diabetes: pooled analysis of sustain 6 and leader","volume":"145","author":"Shaman","year":"2022","journal-title":"Circulation"},{"key":"B65","doi-asserted-by":"publisher","first-page":"251","DOI":"10.1016\/s2213-8587(17)30013-x","article-title":"Efficacy and safety of once-weekly semaglutide monotherapy versus placebo in patients with type 2 diabetes (sustain 1): a double-blind, randomised, placebo-controlled, parallel-group, multinational, multicentre phase 3a trial","volume":"5","author":"Sorli","year":"2017","journal-title":"lancet Diabetes and Endocrinol."},{"key":"B66","doi-asserted-by":"publisher","first-page":"109119","DOI":"10.1016\/j.diabres.2021.109119","article-title":"Idf diabetes atlas: global, regional and country-level diabetes prevalence estimates for 2021 and projections for 2045","volume":"183","author":"Sun","year":"2022","journal-title":"Diabetes Res. Clin. Pract."},{"key":"B67","doi-asserted-by":"publisher","first-page":"981","DOI":"10.1007\/s43440-024-00629-x","article-title":"A review of serious adverse events linked with glp-1 agonists in type 2 diabetes mellitus and obesity treatment","volume":"76","author":"Tobaiqy","year":"2024","journal-title":"Pharmacol. Rep. P. R."},{"key":"B68","doi-asserted-by":"publisher","first-page":"2024.06.25.24309477","DOI":"10.1101\/2024.06.25.24309477","article-title":"Exploiting multivariate network meta-analysis: a calibrated bayesian composite likelihood inference","author":"Wang","year":"2024","journal-title":"medRxiv."},{"key":"B69","doi-asserted-by":"publisher","first-page":"2159","DOI":"10.2337\/dc13-2760","article-title":"Efficacy and safety of dulaglutide added onto pioglitazone and metformin versus exenatide in type 2 diabetes in a randomized controlled trial (Award-1)","volume":"37","author":"Wysham","year":"2014","journal-title":"Diabetes care"},{"key":"B70","doi-asserted-by":"publisher","first-page":"392","DOI":"10.1016\/s2213-8587(20)30074-7","article-title":"Safety and efficacy of oral semaglutide versus dulaglutide in Japanese patients with type 2 diabetes (pioneer 10): an open-label, randomised, active-controlled, phase 3a trial","volume":"8","author":"Yabe","year":"2020","journal-title":"lancet Diabetes and Endocrinol."},{"key":"B71","doi-asserted-by":"publisher","first-page":"377","DOI":"10.1016\/s2213-8587(20)30075-9","article-title":"Dose-response, efficacy, and safety of oral semaglutide monotherapy in Japanese patients with type 2 diabetes (pioneer 9): a 52-week, phase 2\/3a, randomised, controlled trial","volume":"8","author":"Yamada","year":"2020","journal-title":"lancet Diabetes and Endocrinol."},{"key":"B72","doi-asserted-by":"publisher","first-page":"335","DOI":"10.1111\/dom.13072","article-title":"Efficacy and safety of lixisenatide in a predominantly asian population with type 2 diabetes insufficiently controlled with basal insulin: the getgoal-L-C randomized trial","volume":"20","author":"Yang","year":"2018","journal-title":"Diabetes, Obes. and metabolism"},{"key":"B73","doi-asserted-by":"publisher","first-page":"726","DOI":"10.1002\/dmrr.2541","article-title":"Lixisenatide treatment improves glycaemic control in asian patients with type 2 diabetes mellitus inadequately controlled on metformin with or without sulfonylurea: a randomized, double-blind, placebo-controlled, 24-week trial (Getgoal-M-Asia)","volume":"30","author":"Yu Pan","year":"2014","journal-title":"Diabetes\/metabolism Res. Rev."},{"key":"B74","doi-asserted-by":"publisher","first-page":"356","DOI":"10.1016\/s2213-8587(19)30066-x","article-title":"Semaglutide once weekly as add-on to sglt-2 inhibitor therapy in type 2 diabetes (sustain 9): a randomised, placebo-controlled trial","volume":"7","author":"Zinman","year":"","journal-title":"lancet Diabetes and Endocrinol."},{"key":"B75","doi-asserted-by":"publisher","first-page":"2262","DOI":"10.2337\/dc19-0898","article-title":"Efficacy, safety, and tolerability of oral semaglutide versus placebo added to insulin with or without metformin in patients with type 2 diabetes: the pioneer 8 trial","volume":"42","author":"Zinman","year":"","journal-title":"Diabetes care"}],"container-title":["Frontiers in Pharmacology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2025.1613610\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,9,19]],"date-time":"2025-09-19T08:28:25Z","timestamp":1758270505000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2025.1613610\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,9,19]]},"references-count":75,"alternative-id":["10.3389\/fphar.2025.1613610"],"URL":"https:\/\/doi.org\/10.3389\/fphar.2025.1613610","relation":{},"ISSN":["1663-9812"],"issn-type":[{"value":"1663-9812","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,9,19]]},"article-number":"1613610"}}