{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T22:37:53Z","timestamp":1792449473507,"version":"4.5.0"},"reference-count":328,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2025,12,10]],"date-time":"2025-12-10T00:00:00Z","timestamp":1765324800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>Obesity is a multifaceted disease that significantly increases the risk of various chronic conditions. GLP-1R (co)-agonists first emerged as therapeutics for treatment of type 2 diabetes mellitus and have since become an established drug class for improving glycemic control. The interest in GLP-1 for obesity treatment has surged in 2015 after the approval of Saxenda\u00ae (liraglutide). To date, GLP-1 analogs are primarily administered by s.c. injection, which poses a significant burden on patient compliance. To address this challenge, research has focused on oral delivery. This review provides a concise overview of the techniques explored to enhance the oral delivery of GLP-1 analogs for the treatment of obesity. Relevant strategies include the following: (1) the use of permeation enhancers to increase gastrointestinal absorption of peptides; (2) micro- and nanocarriers loaded with GLP-1, including targeted delivery systems and general techniques for active drug targeting; (3) GLP-1 gene delivery; and (4) advanced microbiome systems for GLP-1 delivery. The potential for misuse and side-effects of GLP-1 analogs are also discussed.<\/jats:p>","DOI":"10.3390\/pharmaceutics17121596","type":"journal-article","created":{"date-parts":[[2025,12,11]],"date-time":"2025-12-11T08:39:18Z","timestamp":1765442358000},"page":"1596","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Oral Treatment of Obesity by GLP-1 and Its Analogs"],"prefix":"10.3390","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-1775-9434","authenticated-orcid":false,"given":"Natasa","family":"Holler","sequence":"first","affiliation":[{"name":"Institute of Pharmaceutical Sciences, Pharmaceutical Technology & Biopharmacy, University of Graz, 8010 Graz, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8836-0398","authenticated-orcid":false,"given":"Ivana","family":"Ruseska","sequence":"additional","affiliation":[{"name":"Institute of Pharmaceutical Sciences, Pharmaceutical Technology & Biopharmacy, University of Graz, 8010 Graz, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna-Laurence","family":"Schachner-Nedherer","sequence":"additional","affiliation":[{"name":"Institute of Pharmaceutical Sciences, Pharmaceutical Technology & Biopharmacy, University of Graz, 8010 Graz, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3127-287X","authenticated-orcid":false,"given":"Andreas","family":"Zimmer","sequence":"additional","affiliation":[{"name":"Institute of Pharmaceutical Sciences, Pharmaceutical Technology & Biopharmacy, University of Graz, 8010 Graz, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-6983-9864","authenticated-orcid":false,"given":"Christina","family":"Petschacher","sequence":"additional","affiliation":[{"name":"Institute of Pharmaceutical Sciences, Pharmaceutical Technology & Biopharmacy, University of Graz, 8010 Graz, Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,12,10]]},"reference":[{"key":"ref_1","unstructured":"WHO (2025, November 20). New WHO\/Europe Fact Sheet Highlights Worrying Post-COVID Trends in Childhood Obesity. Available online: https:\/\/www.who.int\/europe\/news\/item\/29-11-2024-new-who-europe-fact-sheet-highlights-worrying-post-covid-trends-in-childhood-obesity."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1016\/j.semcancer.2023.03.008","article-title":"Excess body weight: Novel insights into its roles in obesity comorbidities","volume":"92","author":"Zhang","year":"2023","journal-title":"Semin. Cancer Biol."},{"key":"ref_3","unstructured":"WHO (2025, November 20). One in Eight People Are Now Living with Obesity. Volume 45. Available online: https:\/\/www.who.int\/news\/item\/01-03-2024-one-in-eight-people-are-now-living-with-obesity."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Novelli, G., Cassadonte, C., Sbraccia, P., and Biancolella, M. (2023). Genetics: A Starting Point for the Prevention and the Treatment of Obesity. Nutrients, 15.","DOI":"10.3390\/nu15122782"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"100653","DOI":"10.1016\/j.tvir.2020.100653","article-title":"Obesity: Scope, Lifestyle Interventions, and Medical Management","volume":"23","author":"McCafferty","year":"2020","journal-title":"Tech. Vasc. Interv. Radiol."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Lin, X., and Li, H. (2021). Obesity: Epidemiology, Pathophysiology, and Therapeutics. Front. Endocrinol., 12.","DOI":"10.3389\/fendo.2021.706978"},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Chandrasekaran, P., and Weiskirchen, R. (2024). The Role of Obesity in Type 2 Diabetes Mellitus\u2014An Overview. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25031882"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1080\/21623945.2020.1870060","article-title":"Brown and beige adipose tissue: A novel therapeutic strategy for obesity and type 2 diabetes mellitus","volume":"10","author":"Cheng","year":"2021","journal-title":"Adipocyte"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1038\/nrd.2016.31","article-title":"Convertible visceral fat as a therapeutic target to curb obesity","volume":"15","author":"Giordano","year":"2016","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Schachner-Nedherer, A.L., Fuchs, J., Vidakovic, I., H\u00f6ller, O., Schratter, G., Almer, G., Fr\u00f6hlich, E., Zimmer, A., Wabitsch, M., and Kornmueller, K. (2023). Lipid Nanoparticles as a Shuttle for Anti-Adipogenic miRNAs to Human Adipocytes. Pharmaceutics, 15.","DOI":"10.3390\/pharmaceutics15071983"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1093\/toxsci\/kfaa042","article-title":"Obesity as a source of endogenous compounds associated with chronic disease: A review","volume":"175","author":"Smith","year":"2020","journal-title":"Toxicol. Sci."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"639","DOI":"10.1038\/nrd.2016.75","article-title":"Targeting adipose tissue in the treatment of obesity-associated diabetes","volume":"15","author":"Kusminski","year":"2016","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"433","DOI":"10.1038\/s41366-024-01473-y","article-title":"What is the pipeline for future medications for obesity?","volume":"49","author":"Melson","year":"2024","journal-title":"Int. J. Obes."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Pipek, L.Z., Moraes, W.A.F., Nobetani, R.M., Cortez, V.S., Condi, A.S., Taba, J.V., Nascimento, R.F.V., Suzuki, M.O., do Nascimento, F.S., and de Mattos, V.C. (2024). Surgery is associated with better long-term outcomes than pharmacological treatment for obesity: A systematic review and meta-analysis. Sci. Rep., 14.","DOI":"10.1038\/s41598-024-57724-5"},{"key":"ref_15","unstructured":"WHO (2025, January 30). Obesity and Overweight. Available online: https:\/\/www.who.int\/news-room\/fact-sheets\/detail\/obesity-and-overweight."},{"key":"ref_16","unstructured":"Brown -Chair, W., Kow, L., Mehran Anvari, A., Amir Ghaferi, C., John Morton, U., Scott Shikora, U., Ronald Liem, U., Himpens, J., Mario Musella, B., and Francois Pattou, I. (2025, January 30). 8-th Global Registry Report of the IFSO Global Registry Committee. Available online: https:\/\/www.ifso.com\/pdf\/8th-ifso-registry-report-2024-latest-new.pdf."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"111651","DOI":"10.1016\/j.diabres.2024.111651","article-title":"Bariatrics and endoscopic therapies for the treatment of metabolic disease: Past, present, and future","volume":"211","author":"Mingrone","year":"2024","journal-title":"Diabetes Res. Clin. Pract."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"114","DOI":"10.1016\/j.peptides.2017.12.010","article-title":"Intestinal peptide changes after bariatric and minimally invasive surgery: Relation to diabetes remission","volume":"100","author":"Mingrone","year":"2018","journal-title":"Peptides"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"437","DOI":"10.1055\/a-2292-2494","article-title":"American Society for Gastrointestinal Endoscopy-European Society of Gastrointestinal Endoscopy guideline on primary endoscopic bariatric and metabolic therapies for adults with obesity","volume":"56","author":"Jirapinyo","year":"2024","journal-title":"Endoscopy"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"614","DOI":"10.1002\/oby.23338","article-title":"Roux-en-Y gastric bypass, sleeve gastrectomy, or one-anastomosis gastric bypass? A systematic review and meta-analysis of randomized-controlled trials","volume":"30","author":"Uhe","year":"2022","journal-title":"Obesity"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"e1474","DOI":"10.1590\/0102-672020190001e1474","article-title":"Weight loss comparison after sleeve and roux-en-y gastric bypass: Systematic review","volume":"32","year":"2019","journal-title":"Abcd-Arquivos Bras. Cir. Dig. Arch. Dig. Surg."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1503","DOI":"10.2337\/dc21-2498","article-title":"Effect of Banded Roux-en-Y Gastric Bypass Versus Sleeve Gastrectomy on Diabetes Remission at 5 Years Among Patients With Obesity and Type 2 Diabetes: A Blinded Randomized Clinical Trial","volume":"45","author":"Murphy","year":"2022","journal-title":"Diabetes Care"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1409","DOI":"10.1016\/j.soard.2021.04.010","article-title":"Sleeve gastrectomy versus Roux-en-Y gastric bypass in patients Aged \u2265 65 years: A comparison of short-term outcomes","volume":"17","author":"Frieder","year":"2021","journal-title":"Surg. Obes. Relat. Dis."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"2715","DOI":"10.1007\/s00268-022-06664-0","article-title":"Comparative Safety of Sleeve Gastrectomy and Roux-en-Y: A Propensity Score Analysis","volume":"46","author":"Alalwan","year":"2022","journal-title":"World J. Surg."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"155741","DOI":"10.1016\/j.metabol.2023.155741","article-title":"Advances in obesity pharmacotherapy; learning from metabolic surgery and beyond","volume":"151","author":"Tsilingiris","year":"2024","journal-title":"Metabolism"},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Sz\u00e9kely, M., So\u00f3s, S., P\u00e9terv\u00e1ri, E., and Balask\u00f3, M. (2016). Nutritional Impact on Anabolic and Catabolic Signaling. Molecular Basis of Nutrition and Aging: A Volume in the Molecular Nutrition Series, Elsevier Inc.","DOI":"10.1016\/B978-0-12-801816-3.00014-5"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1007\/s13679-023-00546-9","article-title":"Phentermine in the Modern Era of Obesity Pharmacotherapy: Does It Still Have a Role in Treatment?","volume":"13","author":"Lewis","year":"2024","journal-title":"Curr. Obes. Rep."},{"key":"ref_28","unstructured":"FDA (2024, September 06). drugs@FDA: FDA-Approved Drugs, Available online: www.fda.gov\/drugsatfda."},{"key":"ref_29","unstructured":"EMA\u2014Pharmacovigilance Risk Assessment Committee (PRAC) (2024, September 05). Withdrawal of Marketing Authorisations for Amfepramone Medicines Within the EU. EMA\/867253\/2022. Available online: https:\/\/www.ema.europa.eu\/en\/medicines\/human\/referrals\/amfepramone-containing-medicinal-products."},{"key":"ref_30","unstructured":"Center for Drug Evaluation and Research (CDER) (2025, June 13). Contrave: FDA Approval\u2014Prescribing Information\u2014SUPPL-22, Available online: https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/label\/2024\/200063s022lbl.pdf."},{"key":"ref_31","unstructured":"EMA: Committee for Medicinal Products for Human Use (CHMP) (2025, November 20). Assessment Report\u2014Qsiva. Available online: https:\/\/www.ema.europa.eu\/en\/documents\/assessment-report\/qsiva-epar-public-assessment-report_en.pdf."},{"key":"ref_32","unstructured":"Center for Drug Evaluation and Research (CDER) (2025, June 13). Qsymia: FDA Approval\u2014Prescribing Information\u2014ORIG-1, Available online: https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/label\/2012\/022580s000lbl.pdf."},{"key":"ref_33","unstructured":"EMA\u2014Human Medicines Evaluation Division (2024, September 06). Phentermine\/topiramate: PSUSA\/00010956\/202307\u2014Periodic Safety Update Report Single Assessment. Available online: https:\/\/www.ema.europa.eu\/en\/medicines\/psusa\/psusa-00010956-202307."},{"key":"ref_34","unstructured":"EMA: Committee for Medicinal Products for Human Use (CHMP) (2024, September 06). EMA Starts Review of Weight Management Medicine Mysimba. Available online: https:\/\/www.ema.europa.eu\/en\/documents\/referral\/mysimba-article-20-procedure-ema-starts-review-weight-management-medicine-mysimba_en.pdf."},{"key":"ref_35","unstructured":"EMA: Committee for Medicinal Products for Human Use (CHMP) (2025, June 13). Assessment Report\u2014Mysimba. Available online: https:\/\/www.ema.europa.eu\/en\/documents\/variation-report\/mysimba-h-20-1530-c-3687-0065-epar-assessment-report_en.pdf."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"105649","DOI":"10.1016\/j.phrs.2021.105649","article-title":"Pharmacotherapy of obesity: An update","volume":"169","author":"Cignarella","year":"2021","journal-title":"Pharmacol. Res."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1631","DOI":"10.1038\/s41366-021-00839-w","article-title":"Efficacy of dietary supplements containing isolated organic compounds for weight loss: A systematic review and meta-analysis of randomised placebo-controlled trials","volume":"45","author":"Bessell","year":"2021","journal-title":"Int. J. Obes."},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Al Musaimi, O. (2024). Exploring FDA-Approved Frontiers: Insights into Natural and Engineered Peptide Analogues in the GLP-1, GIP, GHRH, CCK, ACTH, and \u03b1-MSH Realms. Biomolecules, 14.","DOI":"10.3390\/biom14030264"},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"van Santen, H.M., Denzer, C., and M\u00fcller, H.L. (2024). Could setmelanotide be the game-changer for acquired hypothalamic obesity?. Front. Endocrinol., 14.","DOI":"10.3389\/fendo.2023.1307889"},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Jimenez-Munoz, C.M., L\u00f3pez, M., Albericio, F., and Makowski, K. (2021). Targeting energy expenditure\u2014Drugs for obesity treatment. Pharmaceuticals, 14.","DOI":"10.3390\/ph14050435"},{"key":"ref_41","unstructured":"EMA: Committee for Medicinal Products for Human Use (CHMP) (2025, June 13). Assessment Report\u2014Imcivree. Available online: https:\/\/www.ema.europa.eu\/en\/documents\/assessment-report\/imcivree-epar-public-assessment-report_en.pdf."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1007\/s11892-015-0702-6","article-title":"Wolfram Syndrome: Diagnosis, Management, and Treatment","volume":"16","author":"Urano","year":"2016","journal-title":"Curr. Diabetes Rep."},{"key":"ref_43","unstructured":"Center for Drug Evaluation and Research (CDER) (2025, June 13). Saxenda: FDA Approval\u2014Prescribing Information\u2014SUPPL-19, Available online: https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/label\/2024\/206321s019lbl.pdf."},{"key":"ref_44","unstructured":"(2025, October 30). Center for Drug Evaluation and Research (CDER) Victoza: FDA Approval\u2014Prescribing Information\u2014SUPPL-46, Available online: https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/label\/2025\/022341s046lbl.pdf."},{"key":"ref_45","unstructured":"Center for Drug Evaluation and Research (CDER) (2025, June 13). Wegovy: FDA Approval\u2014Prescribing Information\u2014SUPPL-15, Available online: https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/label\/2024\/215256s015lbl.pdf."},{"key":"ref_46","unstructured":"Center for Drug Evaluation and Research (CDER) (2025, June 13). Ozempic: FDA Approval\u2014Prescribing Information\u2014SUPPL-32, Available online: https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/label\/2024\/209637s032lbl.pdf."},{"key":"ref_47","unstructured":"Center for Drug Evaluation and Research (CDER) (2025, June 13). Rybelsus: FDA approval\u2014Prescribing Information\u2014SUPPL-23, Available online: https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/label\/2024\/213051s023lbl.pdf."},{"key":"ref_48","unstructured":"Center for Drug Evaluation and Research (CDER) (2025, June 13). Rybelsus: FDA approval\u2014Prescribing Information\u2014SUPPL-21, Available online: https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/label\/2025\/213051Orig1s020,213051Orig1s021lbl.pdf."},{"key":"ref_49","unstructured":"EMA: Committee for Medicinal Products for Human Use (CHMP) (2025, June 13). Rybelsus\u2014Product Information. 2024 Nov. Available online: https:\/\/www.ema.europa.eu\/en\/documents\/product-information\/rybelsus-epar-product-information_en.pdf."},{"key":"ref_50","unstructured":"European Commission (2025, January 15). Union Register of Medicinal Products\u2014Public Health\u2014European Commission. Available online: https:\/\/ec.europa.eu\/health\/documents\/community-register\/html\/h1430.htm."},{"key":"ref_51","unstructured":"EMA: Committee for Medicinal Products for Human Use (CHMP) (2025, June 13). Mounjaro\u2014Product Information. Available online: https:\/\/www.ema.europa.eu\/en\/documents\/product-information\/mounjaro-epar-product-information_en.pdf."},{"key":"ref_52","unstructured":"EMA: Committee for Medicinal Products for Human Use (CHMP) (2025, January 15). Meeting Highlights from the Committee for Medicinal Products for Human Use. Available online: https:\/\/www.ema.europa.eu\/en\/news\/meeting-highlights-committee-medicinal-products-human-use-chmp-9-12-december-2024."},{"key":"ref_53","unstructured":"Center for Drug Evaluation and Research (CDER) (2025, June 13). Zepbound: FDA Approval\u2014Prescribing Information\u2014SUPPL-13, Available online: https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/label\/2024\/217806s013lbl.pdf."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1409","DOI":"10.1152\/physrev.00034.2006","article-title":"The physiology of glucagon-like peptide 1","volume":"87","author":"Holst","year":"2007","journal-title":"Physiol. Rev."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1016\/j.addr.2018.07.009","article-title":"Battle of GLP-1 delivery technologies","volume":"130","author":"Yu","year":"2018","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1016\/j.molmet.2019.09.010","article-title":"Glucagon-like peptide 1 (GLP-1)","volume":"30","author":"Finan","year":"2019","journal-title":"Mol. Metab."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"954","DOI":"10.1124\/pr.115.011395","article-title":"Glucagon-like peptide-1 and its class B G protein-coupled receptors: A long march to therapeutic successes","volume":"68","author":"Donnelly","year":"2016","journal-title":"Pharmacol. Rev."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"S73","DOI":"10.1016\/S1262-3636(08)73398-6","article-title":"GLP-1 receptor signaling: Effects on pancreatic \u03b2-cell proliferation and survival","volume":"34","author":"Buteau","year":"2008","journal-title":"Diabetes Metab."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"728","DOI":"10.1038\/nrendo.2012.140","article-title":"GLP-1 receptor agonists for individualized treatment of type 2 diabetes mellitus","volume":"8","author":"Meier","year":"2012","journal-title":"Nat. Rev. Endocrinol."},{"key":"ref_60","doi-asserted-by":"crossref","unstructured":"Fusco, J., Xiao, X., Prasadan, K., Sheng, Q., Chen, C., Ming, Y.C., and Gittes, G. (2017). GLP-1\/Exendin-4 induces \u03b2-cell proliferation via the epidermal growth factor receptor. Sci. Rep., 7.","DOI":"10.1038\/s41598-017-09898-4"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1816","DOI":"10.2337\/db09-0063","article-title":"Glucagon-like peptide-1 protects \u03b2-cells against apoptosis by increasing the activity of an Igf-2\/Igf-1 receptor autocrine loop","volume":"58","author":"Cornu","year":"2009","journal-title":"Diabetes"},{"key":"ref_62","doi-asserted-by":"crossref","unstructured":"Costes, S., Bertrand, G., and Ravier, M.A. (2021). Mechanisms of beta-cell apoptosis in type 2 diabetes-prone situations and potential protection by glp-1-based therapies. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22105303"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"871","DOI":"10.1016\/j.cmet.2013.10.014","article-title":"Role of KATP channels in glucose-regulated glucagon secretion and impaired counterregulation in type 2 diabetes","volume":"18","author":"Zhang","year":"2013","journal-title":"Cell Metab."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"1731","DOI":"10.1007\/s00125-017-4315-2","article-title":"The role of somatostatin in GLP-1-induced inhibition of glucagon secretion in mice","volume":"60","author":"Holst","year":"2017","journal-title":"Diabetologia"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"e13852","DOI":"10.14814\/phy2.13852","article-title":"GLP-1 suppresses glucagon secretion in human pancreatic alpha-cells by inhibition of P\/Q-type Ca2+ channels","volume":"6","author":"Ramracheya","year":"2018","journal-title":"Physiol. Rep."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1007\/s11154-014-9289-5","article-title":"Effects of GLP-1 on appetite and weight","volume":"15","author":"Shah","year":"2014","journal-title":"Rev. Endocr. Metab. Disord."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"727","DOI":"10.1002\/ueg2.12097","article-title":"The gastrointestinal tract in hunger and satiety signalling","volume":"9","author":"Tack","year":"2021","journal-title":"United Eur. Gastroenterol. J."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"665","DOI":"10.1210\/en.2017-00812","article-title":"Characterization of the glucagonlike peptide-1 receptor in male mouse brain using a novel antibody and in situ hybridization","volume":"159","author":"Jensen","year":"2018","journal-title":"Endocrinology"},{"key":"ref_69","doi-asserted-by":"crossref","unstructured":"Svegliati-Baroni, G., Patr\u00edcio, B., Lioci, G., Macedo, M.P., and Gastaldelli, A. (2020). Gut-pancreas-liver axis as a target for treatment of nafld\/nash. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21165820"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"e235","DOI":"10.1038\/nutd.2016.44","article-title":"Effects of Exendin-4 on human adipose tissue inflammation and ECM remodelling","volume":"6","author":"Pastel","year":"2016","journal-title":"Nutr. Diabetes"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"1165","DOI":"10.1159\/000478872","article-title":"GLP-1\/GLP-1R Signaling in Regulation of Adipocyte Differentiation and Lipogenesis","volume":"42","author":"Chen","year":"2017","journal-title":"Cell. Physiol. Biochem."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"1429","DOI":"10.3892\/ijmm.2013.1350","article-title":"Glucagon-like peptide 1 regulates adipogenesis in 3T3-L1 preadipocytes","volume":"31","author":"Yang","year":"2013","journal-title":"Int. J. Mol. Med."},{"key":"ref_73","doi-asserted-by":"crossref","unstructured":"Green, C.J., Henriksen, T.I., Pedersen, B.K., and Solomon, T.P.J. (2012). Glucagon Like Peptide-1-Induced Glucose Metabolism in Differentiated Human Muscle Satellite Cells Is Attenuated by Hyperglycemia. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0044284"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1042\/CS20130708","article-title":"GLP-1 at physiological concentrations recruits skeletal and cardiac muscle microvasculature in healthy humans","volume":"127","author":"Subaran","year":"2014","journal-title":"Clin. Sci."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"e13073","DOI":"10.14814\/phy2.13073","article-title":"Glucagon-like peptide-1 elicits vasodilation in adipose tissue and skeletal muscle in healthy men","volume":"5","author":"Asmar","year":"2017","journal-title":"Physiol. Rep."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1042\/BJ20050113","article-title":"The signal peptide of the rat corticotropin-releasing factor receptor 1 promotes receptor expression but is not essential for establishing a functional receptor","volume":"390","author":"Alken","year":"2005","journal-title":"Biochem. J."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"513","DOI":"10.1152\/physrev.00013.2014","article-title":"Physiology of Proglucagon Peptides: Role of Glucagon and GLP-1 in Health and Disease","volume":"95","author":"Sandoval","year":"2015","journal-title":"Physiol. Rev."},{"key":"ref_78","doi-asserted-by":"crossref","unstructured":"Lafferty, R.A., O\u2019Harte, F.P.M., Irwin, N., Gault, V.A., and Flatt, P.R. (2021). Proglucagon-Derived Peptides as Therapeutics. Front. Endocrinol., 12.","DOI":"10.3389\/fendo.2021.689678"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"12826","DOI":"10.1016\/S0021-9258(18)51561-1","article-title":"Complete Sequences of Glucagon-like Peptide-1 from Human and Pig Small Intestine","volume":"264","author":"Bersani","year":"1989","journal-title":"J. Biol. Chem."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"1300","DOI":"10.1016\/S0140-6736(87)91194-9","article-title":"Glucagon-like Peptide-1 7-36: A Physiological Incretin in Man","volume":"330","author":"Kreymann","year":"1987","journal-title":"Lancet"},{"key":"ref_81","doi-asserted-by":"crossref","unstructured":"Cheng, L., Xia, F., Li, Z., Shen, C., Yang, Z., Hou, H., Sun, S., Feng, Y., Yong, X., and Tian, X. (2023). Structure, function and drug discovery of GPCR signaling. Mol. Biomed., 4.","DOI":"10.1186\/s43556-023-00156-w"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"103","DOI":"10.2174\/138945012798868434","article-title":"The Family B1 GPCR: Structural Aspects and Interaction with Accessory Proteins","volume":"13","author":"Couvineau","year":"2012","journal-title":"Curr. Drug Targets"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1016\/S1359-6446(05)03370-2","article-title":"Mechanisms of peptide and nonpeptide ligand binding to Class B G-protein-coupled receptors","volume":"10","author":"Hoare","year":"2005","journal-title":"Drug Discov. Today"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"5356","DOI":"10.1210\/endo.140.11.7143","article-title":"Glucagon-Like Peptide-1-(7-36)Amide Is Transformed to Glucagon-Like Peptide-1-(9-36)Amide by Dipeptidyl Peptidase IV in the Capillaries Supplying the L Cells of the Porcine Intestine","volume":"140","author":"Hansen","year":"1999","journal-title":"Endocrinology"},{"key":"ref_85","first-page":"952","article-title":"Degradation of Glucagon-Like Peptide-l by Human Plasma in Vitro Yields an N-Terminally Truncated Peptide That Is a Major Endogenous Metabolite in Vivo","volume":"80","author":"Deacon","year":"1995","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_86","doi-asserted-by":"crossref","unstructured":"Kim, N.H., Yu, T., and Lee, D.H. (2014). The nonglycemic actions of dipeptidyl peptidase-4 inhibitors. BioMed Res. Int., 2014.","DOI":"10.1155\/2014\/368703"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"429","DOI":"10.1016\/S0014-2999(96)00795-9","article-title":"Glucagon-like peptide-1-(9-36) amide is a major metabolite of glucagon-like peptide-1-(7-36) amide after in vivo administration to dogs, and it acts as an antagonist on the pancreatic receptor","volume":"318","author":"Knudsen","year":"1996","journal-title":"Eur. J. Pharmacol."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"927","DOI":"10.1016\/j.cmet.2017.02.008","article-title":"The Role of Pancreatic Preproglucagon in Glucose Homeostasis in Mice","volume":"25","author":"Chambers","year":"2017","journal-title":"Cell Metab."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"252","DOI":"10.1038\/nrendo.2017.35","article-title":"Pancreatic GLP1 is involved in glucose regulation","volume":"13","author":"Morris","year":"2017","journal-title":"Nat. Rev. Endocrinol."},{"key":"ref_90","first-page":"786","article-title":"Rapid Oscillations in Plasma Glucagon-Like Peptide-1 (GLP-1) in Humans: Cholinergic Control of GLP-1 Secretion via Muscarinic Receptors","volume":"82","author":"Balks","year":"1997","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"2131","DOI":"10.1053\/j.gastro.2007.03.054","article-title":"Biology of Incretins: GLP-1 and GIP","volume":"132","author":"Baggio","year":"2007","journal-title":"Gastroenterology"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1159\/000201231","article-title":"BGlucagon-Like Peptide-1 and Glucose-Dependent Insulin-Releasing Polypeptide Plasma Levels in Response to Nutrients","volume":"56","author":"Herrmann","year":"1994","journal-title":"Digestion"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1111\/dom.13129","article-title":"Incretin hormones: Their role in health and disease. Vol. 20, Diabetes, Obesity and Metabolism","volume":"20","author":"Nauck","year":"2018","journal-title":"Diabetes Obes. Metab."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1016\/S0167-0115(03)00111-3","article-title":"Both GLP-1 and GIP are insulinotropic at basal and postprandial glucose levels and contribute nearly equally to the incretin effect of a meal in healthy subjects","volume":"114","author":"Krarup","year":"2003","journal-title":"Regul. Pept."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"1640","DOI":"10.2337\/diacare.24.9.1640","article-title":"Impaired Incretin Response After a Mixed Meal Is Associated With Insulin Resistance in Nondiabetic Men","volume":"24","author":"Rask","year":"2001","journal-title":"Diabetes Care"},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1038\/s41574-022-00783-3","article-title":"Beyond the pancreas: Contrasting cardiometabolic actions of GIP and GLP1","volume":"19","author":"Hammoud","year":"2022","journal-title":"Nat. Rev. Endocrinol."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"3353","DOI":"10.1111\/bph.16478","article-title":"Altered desensitization and internalization patterns of rodent versus human glucose-dependent insulinotropic polypeptide (GIP) receptors. An important drug discovery challenge","volume":"182","author":"Gasbjerg","year":"2024","journal-title":"Br. J. Pharmacol."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"113326","DOI":"10.1016\/j.celrep.2023.113326","article-title":"GLP-1 and GIP receptors signal through distinct \u03b2-arrestin 2-dependent pathways to regulate pancreatic \u03b2 cell function","volume":"42","author":"Obeid","year":"2023","journal-title":"Cell Rep."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1152\/physiol.00032.2023","article-title":"Pharmacological Advances in Incretin-Based Polyagonism: What We Know and What We Don\u2019t","volume":"39","author":"Novikoff","year":"2024","journal-title":"Physiology"},{"key":"ref_100","unstructured":"Center for Drug Evaluation and Research (CDER) (2025, June 13). Tanzeum: FDA approval\u2014Prescribing Information\u2014SUPPL-20, Available online: https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/label\/2017\/125431s020lbl.pdf."},{"key":"ref_101","unstructured":"EMA: Committee for Medicinal Products for Human Use (CHMP) (2025, June 13). Eperzan\u2014Product Information. Available online: https:\/\/www.ema.europa.eu\/en\/documents\/product-information\/eperzan-epar-product-information_en.pdf."},{"key":"ref_102","unstructured":"GlaxoSmithKline (2025, April 10). Physician Notification Letter UK-Eperzan\u25bc(Albiglutide): Global Discontinuation of Medicine, Available online: https:\/\/assets.publishing.service.gov.uk\/media\/59f081c6e5274a18bc07411b\/Eperzan_Letter_-_090917.pdf."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"7402","DOI":"10.1016\/S0021-9258(18)42531-8","article-title":"Isolation and characterization of exendin-4, an exendin-3 analogue, from Heloderma suspectum venom. Further evidence for an exendin receptor on dispersed acini from guinea pig pancreas","volume":"267","author":"Engsbli","year":"1992","journal-title":"J. Biol. Chem."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"5830","DOI":"10.1021\/bi062309m","article-title":"Differential structural properties of GLP-1 and exendin-4 determine their relative affinity for the GLP-1 receptor N-terminal extracellular domain","volume":"46","author":"Runge","year":"2007","journal-title":"Biochemistry"},{"key":"ref_105","unstructured":"Center for Drug Evaluation and Research (CDER) (2025, June 13). Byetta: FDA Approval\u2014Prescribing Information\u2014SUPPL-49, Available online: https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/label\/2024\/021773s049lbl.pdf."},{"key":"ref_106","unstructured":"Center for Drug Evaluation and Research (CDER) (2025, June 13). Bydureon BCise: FDA Approval\u2014Prescribing Information\u2014SUPPL-24, Available online: https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/label\/2024\/209210s024lbl.pdf."},{"key":"ref_107","unstructured":"Center for Drug Evaluation and Research (CDER) (2025, June 13). Bydureon: FDA approval\u2014Prescribing Information\u2014SUPPL-35, Available online: https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/label\/2024\/022200s035lbl.pdf."},{"key":"ref_108","unstructured":"Astra Zeneca (2025, November 20). Report: Patent Expiries of Key Marketed Products 2023. Available online: https:\/\/www.astrazeneca.com\/content\/dam\/az\/Investor_Relations\/annual-report-2023\/pdf\/AstraZeneca_Patent_Expiries_of_Key_Marketed_Products_2023.pdf."},{"key":"ref_109","unstructured":"Amneal Pharmaceuticals Inc (2025, April 11). Press Release: Amneal Resubmits DHE Autoinjector New Drug Application and Receives U.S. FDA Approval of Exenatide, its First Generic Injectable GLP-1 Agonist. Available online: https:\/\/investors.amneal.com\/news\/press-releases\/press-release-details\/2024\/Amneal-Resubmits-DHE-Autoinjector-New-Drug-Application-and-Receives-U.S.-FDA-Approval-of-Exenatide-its-First-Generic-Injectable-GLP-1-Agonist\/default.aspx."},{"key":"ref_110","unstructured":"EMA: Committee for Medicinal Products for Human Use (CHMP) (2025, June 13). Lyximia\u2014Product Information. Available online: https:\/\/www.ema.europa.eu\/en\/documents\/product-information\/lyxumia-epar-product-information_en.pdf."},{"key":"ref_111","unstructured":"Center for Drug Evaluation and Research (CDER) (2025, June 13). Adlyxin: FDA Approval\u2014Prescribing Information\u2014SUPPL-9, Available online: https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/label\/2024\/208471s009lbl.pdf."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"1223","DOI":"10.1517\/17460441.2014.942638","article-title":"The design and discovery of lixisenatide for the treatment of type 2 diabetes mellitus","volume":"9","author":"Christensen","year":"2014","journal-title":"Expert Opin. Drug Discov."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"113778","DOI":"10.1016\/j.addr.2021.04.016","article-title":"Prevention of diabetes-associated fibrosis: Strategies in FcRn-targeted nanosystems for oral drug delivery","volume":"175","author":"Azevedo","year":"2021","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"343","DOI":"10.2147\/DMSO.S421527","article-title":"Research Advances in Fusion Protein-Based Drugs for Diabetes Treatment. Diabetes, Metabolic Syndrome and Obesity","volume":"17","author":"Deng","year":"2024","journal-title":"Diabetes Metab. Syndr. Obes. Targets Ther."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"783","DOI":"10.1080\/17425255.2020.1801633","article-title":"Albumin-based drug designs for pharmacokinetic modulation","volume":"16","author":"Pilati","year":"2020","journal-title":"Expert Opin. Drug Metab. Toxicol."},{"key":"ref_116","doi-asserted-by":"crossref","unstructured":"Knudsen, L.B., and Lau, J. (2019). The discovery and development of liraglutide and semaglutide. Front. Endocrinol., 10.","DOI":"10.3389\/fendo.2019.00155"},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"173650","DOI":"10.1016\/j.ejphar.2020.173650","article-title":"Albumin-binding domain extends half-life of glucagon-like peptide-1","volume":"890","author":"Tan","year":"2021","journal-title":"Eur. J. Pharmacol."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1002\/dmrr.1080","article-title":"Engineering and characterization of the long-acting glucagon-like peptide-1 analogue LY2189265, an Fc fusion protein","volume":"26","author":"Glaesner","year":"2010","journal-title":"Diabetes Metab. Res. Rev."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1007\/s40259-015-0133-6","article-title":"Fusion Proteins for Half-Life Extension of Biologics as a Strategy to Make Biobetters","volume":"29","author":"Strohl","year":"2015","journal-title":"BioDrugs"},{"key":"ref_120","unstructured":"Center for Drug Evaluation and Research (CDER) (2025, June 13). Trulicity: FDA Approval\u2014Prescribing Information\u2014SUPPL-62, Available online: https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/label\/2024\/125469s061s062lbl.pdf."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1016\/S1388-1981(99)00148-1","article-title":"Fatty Acid Binding to Human Serum Albumin: New Insights from Crystallographic Studies","volume":"1441","author":"Curry","year":"1999","journal-title":"Biochim Biophys Acta"},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"7370","DOI":"10.1021\/acs.jmedchem.5b00726","article-title":"Discovery of the Once-Weekly Glucagon-Like Peptide-1 (GLP-1) Analogue Semaglutide","volume":"58","author":"Lau","year":"2015","journal-title":"J. Med. Chem."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"498","DOI":"10.1111\/j.1463-1326.2008.00992.x","article-title":"Safety, tolerability, pharmacodynamics and pharmacokinetics of albiglutide, a long-acting glucagon-like peptide-1 mimetic, in healthy subjects","volume":"11","author":"Bush","year":"2009","journal-title":"Diabetes Obes. Metab."},{"key":"ref_124","unstructured":"Center for Drug Evaluation and Research (CDER) (2025, June 13). Mounjaro: FDA Approval\u2014Prescribing Information\u2014ORIG-1, Available online: https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/label\/2022\/215866s000lbl.pdf?1fba97f6_page=3."},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/j.molmet.2018.09.009","article-title":"LY3298176, a novel dual GIP and GLP-1 receptor agonist for the treatment of type 2 diabetes mellitus: From discovery to clinical proof of concept","volume":"18","author":"Coskun","year":"2018","journal-title":"Mol. Metab."},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"e2116506119","DOI":"10.1073\/pnas.2116506119","article-title":"Structural Determinants of Dual Incretin Receptor Agonism by Tirzepatide","volume":"119","author":"Sun","year":"2022","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_127","unstructured":"PubChem (2025, October 29). GLP-1, Available online: https:\/\/pubchem.ncbi.nlm.nih.gov\/compound\/Glucagon-Like-Peptide-1."},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"186","DOI":"10.1016\/j.ejpb.2020.07.003","article-title":"Nasal absorption enhancement of protein drugs independent to their chemical properties in the presence of hyaluronic acid modified with tetraglycine-L-octaarginine","volume":"154","author":"Tomono","year":"2020","journal-title":"Eur. J. Pharm. Biopharm."},{"key":"ref_129","unstructured":"PubChem (2025, October 29). Liraglutide, Available online: https:\/\/pubchem.ncbi.nlm.nih.gov\/compound\/16134956."},{"key":"ref_130","unstructured":"Center for Drug Evaluation and Research (CDER) (2025, October 29). Rybelsus: Product Quality Review(s), Available online: https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/nda\/2019\/213051Orig1s000ChemR.pdf."},{"key":"ref_131","unstructured":"Pubchem (2025, October 29). Semaglutide, Available online: https:\/\/pubchem.ncbi.nlm.nih.gov\/compound\/56843331."},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"e13663","DOI":"10.1111\/obr.13663","article-title":"Management of type 2 diabetes, obesity, or nonalcoholic steatohepatitis with high-dose GLP-1 receptor agonists and GLP-1 receptor-based co-agonists","volume":"25","author":"Goldenberg","year":"2024","journal-title":"Obes. Rev."},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"290","DOI":"10.1038\/s42255-023-00966-w","article-title":"A GIPR antagonist conjugated to GLP-1 analogues promotes weight loss with improved metabolic parameters in preclinical and phase 1 settings","volume":"6","author":"Lu","year":"2024","journal-title":"Nat. Metab."},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"843","DOI":"10.1056\/NEJMoa2504214","article-title":"Once-Monthly Maridebart Cafraglutide for the Treatment of Obesity\u2014A Phase 2 Trial","volume":"393","author":"Jastreboff","year":"2025","journal-title":"N. Engl. J. Med."},{"key":"ref_135","first-page":"566","article-title":"Antagonizing GIPR adds fire to the GLP-1R flame. Trends in Endocrinology and Metabolism","volume":"35","author":"Novikoff","year":"2024","journal-title":"Endocrinol. Metab."},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"4981","DOI":"10.1038\/s41467-020-18751-8","article-title":"Chronic glucose-dependent insulinotropic polypeptide receptor (GIPR) agonism desensitizes adipocyte GIPR activity mimicking functional GIPR antagonism","volume":"11","author":"Killion","year":"2020","journal-title":"Nat. Commun."},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"171212","DOI":"10.1016\/j.peptides.2024.171212","article-title":"GIP-derived GIP receptor antagonists\u2014A review of their role in GIP receptor pharmacology","volume":"177","author":"Rosenkilde","year":"2024","journal-title":"Peptides"},{"key":"ref_138","doi-asserted-by":"crossref","unstructured":"Kleinert, M., Sachs, S., Habegger, K.M., Hofmann, S.M., and M\u00fcller, T.D. (2019). Glucagon regulation of energy expenditure. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20215407"},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1007\/s40265-023-01982-6","article-title":"Poly-Agonist Pharmacotherapies for Metabolic Diseases: Hopes and New Challenges","volume":"84","author":"Allard","year":"2023","journal-title":"Drugs"},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"1736","DOI":"10.1016\/S0140-6736(21)00845-X","article-title":"Safety, tolerability, pharmacokinetics, and pharmacodynamics of concomitant administration of multiple doses of cagrilintide with semaglutide 2\u00b74 mg for weight management: A randomised, controlled, phase 1b trial","volume":"397","author":"Enebo","year":"2021","journal-title":"Lancet"},{"key":"ref_141","doi-asserted-by":"crossref","first-page":"1471","DOI":"10.1111\/dom.14358","article-title":"Safety and efficacy of an extended-release peptide YY analogue for obesity: A randomized, placebo-controlled, phase 1 trial","volume":"23","author":"Tan","year":"2021","journal-title":"Diabetes Obes. Metab."},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"1699","DOI":"10.1038\/ijo.2016.121","article-title":"Peptide YY and glucagon-like peptide-1 contribute to decreased food intake after Roux-en-Y gastric bypass surgery","volume":"40","author":"Svane","year":"2016","journal-title":"Int. J. Obes."},{"key":"ref_143","unstructured":"Novo Nordisk A\/S (2025, January 30). Financial Report for the Period 1 January 2023 to June 2023. Available online: https:\/\/ml-eu.globenewswire.com\/Resource\/Download\/b4ae7c0b-df06-49cd-a1b9-50d5d566e6bc."},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1007\/s40520-024-02825-4","article-title":"Effect of Bimagrumab on body composition: A systematic review and meta-analysis","volume":"36","author":"Kanbay","year":"2024","journal-title":"Aging Clin. Exp. Res."},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"2871","DOI":"10.1128\/MCB.06575-11","article-title":"Blockade of the Activin Receptor IIB Activates Functional Brown Adipogenesis and Thermogenesis by Inducing Mitochondrial Oxidative Metabolism","volume":"32","author":"Fournier","year":"2012","journal-title":"Mol. Cell Biol."},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"e2033457","DOI":"10.1001\/jamanetworkopen.2020.33457","article-title":"Effect of Bimagrumab vs Placebo on Body Fat Mass among Adults with Type 2 Diabetes and Obesity: A Phase 2 Randomized Clinical Trial","volume":"4","author":"Heymsfield","year":"2021","journal-title":"JAMA Netw. Open"},{"key":"ref_147","doi-asserted-by":"crossref","unstructured":"Li, Q., and Kang, C. (2020). Mechanisms of action for small molecules revealed by structural biology in drug discovery. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21155262"},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"911","DOI":"10.1080\/20415990.2024.2414732","article-title":"Industry Update: The latest Developments in the Field of Therapeutic Delivery, July 2024","volume":"15","author":"Timmins","year":"2024","journal-title":"Ther. Deliv."},{"key":"ref_149","unstructured":"Genentech: Press Releases (2025, February 04). Genentech Announces Positive Phase I Results of Its Oral GLP-1 Receptor Agonist CT-996 for the Treatment of People with Obesity. Available online: https:\/\/www.gene.com\/media\/press-releases\/15032\/2024-07-16\/genentech-announces-positive-phase-i-res."},{"key":"ref_150","unstructured":"Carmot Therapeutics Inc (2025, January 30). Carmot Therapeutics Announces Completion of Acquisition by Roche. Available online: https:\/\/carmot.us\/carmot-therapeutics-announces-completion-of-acquisition-by-roche\/."},{"key":"ref_151","doi-asserted-by":"crossref","first-page":"234","DOI":"10.1038\/s41392-024-01931-z","article-title":"Glucagon-like peptide-1 receptor: Mechanisms and advances in therapy","volume":"9","author":"Zheng","year":"2024","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_152","doi-asserted-by":"crossref","first-page":"e140532","DOI":"10.1172\/jci.insight.140532","article-title":"Tirzepatide is an imbalanced and biased dual GIP and GLP-1 receptor agonist","volume":"5","author":"Willard","year":"2020","journal-title":"JCI Insight"},{"key":"ref_153","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1038\/s41392-022-00904-4","article-title":"Therapeutic peptides: Current applications and future directions","volume":"7","author":"Wang","year":"2022","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_154","first-page":"42","article-title":"A Review of Glucagon-like Peptide-1 in Dermatology","volume":"18","author":"Willmar","year":"2025","journal-title":"J. Clin. Aesthet. Dermatol."},{"key":"ref_155","doi-asserted-by":"crossref","unstructured":"Pechenov, S., Revell, J., Will, S., Naylor, J., Tyagi, P., Patel, C., Liang, L., Tseng, L., Huang, Y., and Rosenbaum, A.I. (2021). Development of an orally delivered GLP-1 receptor agonist through peptide engineering and drug delivery to treat chronic disease. Sci. Rep., 11.","DOI":"10.1038\/s41598-021-01750-0"},{"key":"ref_156","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1038\/s41392-024-02107-5","article-title":"Advance in peptide-based drug development: Delivery platforms, therapeutics and vaccines","volume":"10","author":"Xiao","year":"2025","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_157","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1016\/j.addr.2020.05.007","article-title":"Systemic delivery of peptides by the oral route: Formulation and medicinal chemistry approaches","volume":"157","author":"Brayden","year":"2020","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_158","doi-asserted-by":"crossref","first-page":"113675","DOI":"10.1016\/j.jconrel.2025.113675","article-title":"Enzymatic absorption promoters for non-invasive peptide delivery","volume":"382","author":"Steiger","year":"2025","journal-title":"J. Control. Release"},{"key":"ref_159","unstructured":"Lexaria Bioscience Corp (2025, November 06). Lexaria\u2019s DehydraTECH Technology Has the Potential to Unlock Accelerated Revenue Growth in the GLP-1-Industry. Available online: https:\/\/lexariabioscience.com\/2025\/07\/23\/lexarias-dehydratech-technology-has-the-potential-to-unlock-accelerated-revenue-growth-in-the-glp-1-industry."},{"key":"ref_160","unstructured":"Lexaria Bioscience Corp (2025, November 06). ALL Study Groups Using DehydraTECH Processing Outperform Rybelsus\u00ae in Body Weight Control in Lexaria\u2019s 12-Week GLP-1, Diabetes Animal Study. Available online: https:\/\/lexariabioscience.com\/2024\/11\/20\/all-study-groups-using-dehydratech-processing-outperform-rybelsus-in-body-weight-control-in-lexarias-12-week-glp-1-diabetes-animal-study."},{"key":"ref_161","unstructured":"Lexaria Bioscience Corp (2025, November 06). Lexaria\u2019s DehydraTECH-Liraglutide Human GLP-1 Clinical Study Supports Pathway to Potential FDA Registration as an Orally-Delivered Capsule. Available online: https:\/\/lexariabioscience.com\/2025\/06\/11\/lexarias-dehydratech-liraglutide-human-glp-1-clinical-study-supports-pathway-to-potential-fda-registration-as-an-orally-delivered-capsule."},{"key":"ref_162","unstructured":"Lexaria Bioscience Corp (2025, November 06). Lexaria\u2019s Technology Supports Higher Levels of the GLP-1 Drug Semaglutide in Brain. Available online: https:\/\/lexariabioscience.com\/2025\/09\/19\/lexarias-technology-supports-higher-levels-of-the-glp-1-drug-semaglutide-in-brain."},{"key":"ref_163","doi-asserted-by":"crossref","unstructured":"Ke, Z., Ma, Q., Ye, X., Wang, Y., Jin, Y., Zhao, X., and Su, Z. (2024). Peptide GLP-1 receptor agonists: From injection to oral delivery strategies. Biochem. Pharmacol., 229.","DOI":"10.1016\/j.bcp.2024.116471"},{"key":"ref_164","doi-asserted-by":"crossref","unstructured":"Kim, J.C., Park, E.J., and Na, D.H. (2022). Gastrointestinal Permeation Enhancers for the Development of Oral Peptide Pharmaceuticals. Pharmaceuticals, 15.","DOI":"10.3390\/ph15121585"},{"key":"ref_165","doi-asserted-by":"crossref","first-page":"2006","DOI":"10.1016\/j.apsb.2024.02.019","article-title":"Oral peptide therapeutics for diabetes treatment: State-of-the-art and future perspectives","volume":"14","author":"Ding","year":"2024","journal-title":"Acta Pharm. Sin. B"},{"key":"ref_166","doi-asserted-by":"crossref","first-page":"e2400843","DOI":"10.1002\/advs.202400843","article-title":"Gastrointestinal Permeation Enhancers Beyond Sodium Caprate and SNAC\u2014What is Coming Next?","volume":"11","author":"Bohley","year":"2024","journal-title":"Adv. Sci."},{"key":"ref_167","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1016\/j.jconrel.2024.11.078","article-title":"Combining SNAC and C10 in oral tablet formulations for gastric peptide delivery: A preclinical and clinical study","volume":"378","author":"Niu","year":"2025","journal-title":"J. Control. Release"},{"key":"ref_168","doi-asserted-by":"crossref","first-page":"621","DOI":"10.1016\/j.apsb.2021.08.003","article-title":"Fighting type 2 diabetes: Formulation strategies for peptide-based therapeutics","volume":"12","year":"2022","journal-title":"Acta Pharm. Sin. B"},{"key":"ref_169","unstructured":"Emisphere Technologies INC (2025, January 30). Emisphere Reports: First Quarter 2015\u2014Financial Results, Available online: https:\/\/www.sec.gov\/Archives\/edgar\/data\/805326\/000119312515190200\/d925281dex991.htm."},{"key":"ref_170","unstructured":"Novo Nordisk (2025, January 17). Press Release: Novo Nordisk to Acquire Emisphere Technologies and Obtain Ownership of the Eligen\u00ae SNAC Oral Delivery Technology. Available online: https:\/\/www.novonordisk.com\/news-and-media\/news-and-ir-materials\/news-details.html?id=33374."},{"key":"ref_171","doi-asserted-by":"crossref","unstructured":"Twarog, C., Fattah, S., Heade, J., Maher, S., Fattal, E., and Brayden, D.J. (2019). Intestinal permeation enhancers for oral delivery of macromolecules: A comparison between salcaprozate sodium (SNAC) and sodium caprate (c10). Pharmaceutics, 11.","DOI":"10.3390\/pharmaceutics11020078"},{"key":"ref_172","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s13346-021-01000-w","article-title":"Development and approval of rybelsus (oral semaglutide): Ushering in a new era in peptide delivery","volume":"12","author":"Lewis","year":"2022","journal-title":"Drug Deliv. Transl. Res."},{"key":"ref_173","doi-asserted-by":"crossref","first-page":"eabk1792","DOI":"10.1126\/sciadv.abk1792","article-title":"Dynamic omnidirectional adhesive microneedle system for oral macromolecular drug delivery","volume":"8","author":"Chen","year":"2022","journal-title":"Sci. Adv."},{"key":"ref_174","doi-asserted-by":"crossref","first-page":"eaar7047","DOI":"10.1126\/scitranslmed.aar7047","article-title":"Transcellular stomach absorption of a derivatized glucagon-like peptide-1 receptor agonist","volume":"10","author":"Buckley","year":"2018","journal-title":"Sci. Transl. Med."},{"key":"ref_175","doi-asserted-by":"crossref","first-page":"S91","DOI":"10.1016\/S0169-409X(01)00180-6","article-title":"Chitosan and its derivatives as intestinal absorption enhancers","volume":"50","author":"Thanou","year":"2001","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_176","doi-asserted-by":"crossref","first-page":"551","DOI":"10.1080\/1061186X.2017.1400552","article-title":"The role of chitosan on oral delivery of peptide-loaded nanoparticle formulation","volume":"26","author":"Wong","year":"2018","journal-title":"J. Drug Target."},{"key":"ref_177","doi-asserted-by":"crossref","first-page":"843","DOI":"10.1517\/17425247.2.5.843","article-title":"The potential of chitosan for the oral administration of peptides","volume":"2","author":"Prego","year":"2005","journal-title":"Expert Opin. Drug Deliv."},{"key":"ref_178","doi-asserted-by":"crossref","first-page":"15627","DOI":"10.1021\/acsnano.2c05317","article-title":"How Nanoparticles Open the Paracellular Route of Biological Barriers: Mechanisms, Applications, and Prospects","volume":"16","author":"Wu","year":"2022","journal-title":"ACS Nano"},{"key":"ref_179","doi-asserted-by":"crossref","first-page":"6254","DOI":"10.1016\/j.biomaterials.2012.05.013","article-title":"Elucidating the signaling mechanism of an epithelial tight-junction opening induced by chitosan","volume":"33","author":"Hsu","year":"2012","journal-title":"Biomaterials"},{"key":"ref_180","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1016\/j.biomaterials.2015.07.045","article-title":"Multistage pH-responsive mucoadhesive nanocarriers prepared by aerosol flow reactor technology: A controlled dual protein-drug delivery system","volume":"68","author":"Shrestha","year":"2015","journal-title":"Biomaterials"},{"key":"ref_181","doi-asserted-by":"crossref","first-page":"807","DOI":"10.1038\/gt.2011.25","article-title":"Effective and Safe Gene-Based Delivery of GLP-1 Using Chitosan\/Plasmid-DNA Therapeutic Nanocomplexes in an Animal Model of Type 2 Diabetes","volume":"18","author":"Jean","year":"2011","journal-title":"Gene Ther."},{"key":"ref_182","doi-asserted-by":"crossref","unstructured":"Ziebarth, J., da Silva, L.M., Lorenzett, A.K.P., Figueiredo, I.D., Carlstrom, P.F., Cardoso, F.N., de Freitas, A.L.F., Baviera, A.M., and Mainardes, R.M. (2024). Oral Delivery of Liraglutide-Loaded Zein\/Eudragit-Chitosan Nanoparticles Provides Pharmacokinetic and Glycemic Outcomes Comparable to Its Subcutaneous Injection in Rats. Pharmaceutics, 16.","DOI":"10.3390\/pharmaceutics16050634"},{"key":"ref_183","doi-asserted-by":"crossref","unstructured":"Asano, D., Takakusa, H., and Nakai, D. (2023). Oral Absorption of Middle-to-Large Molecules and Its Improvement, with a Focus on New Modality Drugs. Pharmaceutics, 16.","DOI":"10.3390\/pharmaceutics16010047"},{"key":"ref_184","doi-asserted-by":"crossref","unstructured":"Azman, M., Sabri, A.H., Anjani, Q.K., Mustaffa, M.F., and Hamid, K.A. (2022). Intestinal Absorption Study: Challenges and Absorption Enhancement Strategies in Improving Oral Drug Delivery. Pharmaceuticals, 15.","DOI":"10.3390\/ph15080975"},{"key":"ref_185","doi-asserted-by":"crossref","first-page":"2555","DOI":"10.1007\/s11095-022-03372-1","article-title":"Identification of a Multi-Component Formulation for Intestinal Delivery of a GLP-1\/Glucagon Co-agonist Peptide","volume":"39","author":"Tran","year":"2022","journal-title":"Pharm. Res."},{"key":"ref_186","doi-asserted-by":"crossref","first-page":"929","DOI":"10.1021\/acs.molpharmaceut.2c00443","article-title":"In Vivo Mechanism of Action of Sodium Caprate for Improving the Intestinal Absorption of a GLP1\/GIP Coagonist Peptide","volume":"20","author":"Tran","year":"2023","journal-title":"Mol. Pharm."},{"key":"ref_187","doi-asserted-by":"crossref","first-page":"123680","DOI":"10.1016\/j.ijpharm.2023.123680","article-title":"Development and evaluation of C10 and SNAC erodible tablets for gastric delivery of a GIP\/GLP1 peptide in monkeys","volume":"650","author":"Tran","year":"2023","journal-title":"Int. J. Pharm."},{"key":"ref_188","doi-asserted-by":"crossref","first-page":"1021","DOI":"10.1007\/s11095-025-03881-9","article-title":"Controlling Gastric Delivery of a GIP\/GLP1 Peptide in Monkeys by Mucoadhesive SNAC Tablets","volume":"42","author":"Tran","year":"2025","journal-title":"Pharm. Res."},{"key":"ref_189","doi-asserted-by":"crossref","first-page":"4030","DOI":"10.1039\/c2cs15362a","article-title":"Ether- and alcohol-functionalized task-specific ionic liquids: Attractive properties and applications","volume":"41","author":"Tang","year":"2012","journal-title":"Chem. Soc. Rev."},{"key":"ref_190","doi-asserted-by":"crossref","unstructured":"Zhang, X., Pang, G., Sun, T., Liu, X., Pan, H., Zhang, Y., Liu, J., Chang, J., Wang, H., and Liu, D. (2023). A red light-controlled probiotic bio-system for in-situ gut-brain axis regulation. Biomaterials, 294.","DOI":"10.1016\/j.biomaterials.2023.122005"},{"key":"ref_191","doi-asserted-by":"crossref","first-page":"1881","DOI":"10.1039\/C6MD00358C","article-title":"Ionic liquids as a potential tool for drug delivery systems","volume":"7","author":"Adawiyah","year":"2016","journal-title":"Med. Chem. Commun."},{"key":"ref_192","doi-asserted-by":"crossref","first-page":"115157","DOI":"10.1016\/j.addr.2023.115157","article-title":"Potentials of ionic liquids to overcome physical and biological barriers","volume":"204","author":"Beaven","year":"2023","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_193","doi-asserted-by":"crossref","first-page":"2353","DOI":"10.1007\/s11095-022-03260-8","article-title":"Ionic Liquids: Promising Approach for Oral Drug Delivery","volume":"39","author":"Jiang","year":"2022","journal-title":"Pharm. Res."},{"key":"ref_194","doi-asserted-by":"crossref","first-page":"593","DOI":"10.1016\/j.jconrel.2024.10.034","article-title":"Choline geranate (CAGE): A multifaceted ionic liquid for drug delivery","volume":"376","author":"Mitragotri","year":"2024","journal-title":"J. Control. Release"},{"key":"ref_195","doi-asserted-by":"crossref","first-page":"7296","DOI":"10.1073\/pnas.1722338115","article-title":"Ionic liquids for oral insulin delivery","volume":"115","author":"Banerjee","year":"2018","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_196","doi-asserted-by":"crossref","first-page":"2000180","DOI":"10.1002\/adtp.202000180","article-title":"Choline-Geranate Deep Eutectic Solvent Improves Stability and Half-Life of Glucagon-Like Peptide-1","volume":"4","author":"Agatemor","year":"2021","journal-title":"Adv. Ther."},{"key":"ref_197","doi-asserted-by":"crossref","first-page":"391","DOI":"10.4236\/jbnb.2012.33038","article-title":"Preparation of Ionic Liquid Functionalized Silica Nanoparticles for Oral Drug Delivery","volume":"3","author":"Mahkam","year":"2012","journal-title":"J. Biomater. Nanobiotechnol."},{"key":"ref_198","doi-asserted-by":"crossref","first-page":"25042","DOI":"10.1073\/pnas.1914426116","article-title":"Oral ionic liquid for the treatment of diet-induced obesity","volume":"116","author":"Nurunnabi","year":"2019","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_199","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1016\/j.jconrel.2024.11.036","article-title":"Salcaprozate-based ionic liquids for GLP-1 gastric delivery: A mechanistic understanding of in vivo performance","volume":"377","author":"Rebollo","year":"2025","journal-title":"J. Control. Release"},{"key":"ref_200","doi-asserted-by":"crossref","first-page":"214","DOI":"10.1016\/j.ejpb.2018.10.013","article-title":"Pharmacodynamical effects of orally administered exenatide nanoparticles embedded in gastro-resistant microparticles","volume":"133","author":"Naraykin","year":"2018","journal-title":"Eur. J. Pharm. Biopharm."},{"key":"ref_201","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1016\/j.ijpharm.2008.01.015","article-title":"Pharmacokinetics and pharmacodynamics of exenatide following alternate routes of administration","volume":"356","author":"Gedulin","year":"2008","journal-title":"Int. J. Pharm."},{"key":"ref_202","doi-asserted-by":"crossref","first-page":"2973","DOI":"10.2147\/IJN.S442617","article-title":"Coordinated ASBT and EGFR Mechanisms for Optimized Liraglutide Nanoformulation Absorption in the GI Tract","volume":"19","author":"Kweon","year":"2024","journal-title":"Int. J. Nanomed."},{"key":"ref_203","doi-asserted-by":"crossref","first-page":"2673","DOI":"10.1016\/j.biomaterials.2010.12.044","article-title":"The glucose-lowering potential of exendin-4 orally delivered via a pH-sensitive nanoparticle vehicle and effects on subsequent insulin secretion in vivo","volume":"32","author":"Nguyen","year":"2011","journal-title":"Biomaterials"},{"key":"ref_204","doi-asserted-by":"crossref","first-page":"202","DOI":"10.1016\/j.jconrel.2015.09.012","article-title":"Improved oral absorption of exenatide using an original nanoencapsulation and microencapsulation approach","volume":"217","author":"Naraykin","year":"2015","journal-title":"J. Control. Release"},{"key":"ref_205","doi-asserted-by":"crossref","first-page":"226","DOI":"10.1016\/j.jconrel.2013.05.031","article-title":"Oral delivery of an anti-diabetic peptide drug via conjugation and complexation with low molecular weight chitosan","volume":"170","author":"Ahn","year":"2013","journal-title":"J. Control. Release"},{"key":"ref_206","doi-asserted-by":"crossref","first-page":"9199","DOI":"10.1016\/j.biomaterials.2014.07.026","article-title":"The impact of nanoparticles on the mucosal translocation and transport of GLP-1 across the intestinal epithelium","volume":"35","author":"Shrestha","year":"2014","journal-title":"Biomaterials"},{"key":"ref_207","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1016\/j.actbio.2024.12.039","article-title":"Impact of nanoparticle properties on immune cell interactions in the lymph node","volume":"193","author":"Farooq","year":"2025","journal-title":"Acta Biomater."},{"key":"ref_208","doi-asserted-by":"crossref","unstructured":"Pinto, S.F.T., Santos, H.A., and Sarmento, B.F.C.C. (2024). New insights into nanomedicines for oral delivery of glucagon-like peptide-1 analogs. Nanobiotechnology, 16.","DOI":"10.1002\/wnan.1952"},{"key":"ref_209","doi-asserted-by":"crossref","first-page":"213ra167","DOI":"10.1126\/scitranslmed.3007049","article-title":"Transepithelial transport of Fc-targeted nanoparticles by the neonatal Fc receptor for oral delivery","volume":"5","author":"Pridgen","year":"2013","journal-title":"Sci. Transl. Med."},{"key":"ref_210","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1016\/S1359-6446(04)03333-1","article-title":"Transferrin: Structure, function and potential therapeutic actions","volume":"10","year":"2005","journal-title":"Drug. Discov. Today"},{"key":"ref_211","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1111\/pbi.12149","article-title":"A fusion protein derived from plants holds promising potential as a new oral therapy for type 2 diabetes","volume":"12","author":"Choi","year":"2014","journal-title":"Plant Biotechnol. J."},{"key":"ref_212","doi-asserted-by":"crossref","first-page":"210","DOI":"10.1016\/j.jbiotec.2008.01.021","article-title":"Identification of a peptide sequence that improves transport of macromolecules across the intestinal mucosal barrier targeting goblet cells","volume":"135","author":"Kang","year":"2008","journal-title":"J. Biotechnol."},{"key":"ref_213","doi-asserted-by":"crossref","first-page":"518","DOI":"10.1021\/acs.molpharmaceut.8b00809","article-title":"Synthesis of CSK-DEX-PLGA Nanoparticles for the Oral Delivery of Exenatide to Improve Its Mucus Penetration and Intestinal Absorption","volume":"16","author":"Song","year":"2019","journal-title":"Mol. Pharm."},{"key":"ref_214","doi-asserted-by":"crossref","first-page":"1573","DOI":"10.1016\/j.biomaterials.2011.10.075","article-title":"Goblet cell-targeting nanoparticles for oral insulin delivery and the influence of mucus on insulin transport","volume":"33","author":"Jin","year":"2012","journal-title":"Biomaterials"},{"key":"ref_215","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1016\/j.ejpb.2023.09.003","article-title":"Double layer spherical nanoparticles with hyaluronic acid coating to enhance oral delivery of exenatide in T2DM rats","volume":"191","author":"Lu","year":"2023","journal-title":"Eur. J. Pharm. Biopharm."},{"key":"ref_216","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1016\/j.mam.2012.12.009","article-title":"The ABCs of membrane transporters in health and disease (SLC series): Introduction","volume":"34","author":"Hediger","year":"2013","journal-title":"Mol. Asp. Med."},{"key":"ref_217","doi-asserted-by":"crossref","first-page":"2181744","DOI":"10.1080\/10717544.2023.2181744","article-title":"Folic acid-modified reverse micelle-lipid nanocapsules overcome intestinal barriers and improve the oral delivery of peptides","volume":"30","author":"He","year":"2023","journal-title":"Drug Deliv."},{"key":"ref_218","doi-asserted-by":"crossref","first-page":"1460","DOI":"10.1016\/j.apsb.2021.07.024","article-title":"The upregulated intestinal folate transporters direct the uptake of ligand-modified nanoparticles for enhanced oral insulin delivery","volume":"12","author":"Li","year":"2022","journal-title":"Acta Pharm. Sin. B"},{"key":"ref_219","doi-asserted-by":"crossref","first-page":"334","DOI":"10.1021\/bc700292v","article-title":"Preparation, characterization, and application of biotinylated and biotin-PEGylated glucagon-like peptide-1 analogues for enhanced oral delivery","volume":"19","author":"Su","year":"2008","journal-title":"Bioconjug Chem."},{"key":"ref_220","doi-asserted-by":"crossref","first-page":"667","DOI":"10.1016\/j.ejpb.2007.07.009","article-title":"Improved peroral delivery of glucagon-like peptide-1 by site-specific biotin modification: Design, preparation, and biological evaluation","volume":"68","author":"Youn","year":"2008","journal-title":"Eur. J. Pharm. Biopharm."},{"key":"ref_221","doi-asserted-by":"crossref","first-page":"1319","DOI":"10.1007\/s001250051529","article-title":"Oral delivery of glucagon-like peptide-1 in a modified polymer preparation normalizes basal glycaemia in diabetic db\/db mice","volume":"43","author":"Joseph","year":"2000","journal-title":"Diabetologia"},{"key":"ref_222","doi-asserted-by":"crossref","unstructured":"Zhang, B., He, D., Fan, Y., Liu, N., and Chen, Y. (2014). Oral Delivery of Exenatide via Microspheres Prepared by Cross-Linking of Alginate and Hyaluronate. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0086064"},{"key":"ref_223","doi-asserted-by":"crossref","first-page":"120583","DOI":"10.1016\/j.ijpharm.2021.120583","article-title":"Utilization of PLGA nanoparticles in yeast cell wall particle system for oral targeted delivery of exenatide to improve its hypoglycemic efficacy","volume":"601","author":"Ren","year":"2021","journal-title":"Int. J. Pharm."},{"key":"ref_224","first-page":"1141","article-title":"Preparation, characterization, and in vitro and in vivo investigation of chitosan-coated poly (d,l-lactide-co-glycolide) nanoparticles for intestinal delivery of exendin-4","volume":"8","author":"Wang","year":"2013","journal-title":"Int. J. Nanomed."},{"key":"ref_225","doi-asserted-by":"crossref","first-page":"8291","DOI":"10.1021\/acsnano.5b02762","article-title":"Microfluidic Assembly of a Multifunctional Tailorable Composite System Designed for Site Specific Combined Oral Delivery of Peptide Drugs","volume":"9","author":"Shrestha","year":"2015","journal-title":"ACS Nano"},{"key":"ref_226","doi-asserted-by":"crossref","first-page":"10706","DOI":"10.1039\/C6NR00294C","article-title":"In vivo dual-delivery of glucagon like peptide-1 (GLP-1) and dipeptidyl peptidase-4 (DPP4) inhibitor through composites prepared by microfluidics for diabetes therapy","volume":"8","author":"Shrestha","year":"2016","journal-title":"Nanoscale"},{"key":"ref_227","doi-asserted-by":"crossref","unstructured":"Shi, Y., Sun, X., Zhang, L., Sun, K., Li, K., Li, Y., and Zhang, Q. (2018). Fc-modified exenatide-loaded nanoparticles for oral delivery to improve hypoglycemic effects in mice. Sci. Rep., 8.","DOI":"10.1038\/s41598-018-19170-y"},{"key":"ref_228","doi-asserted-by":"crossref","first-page":"931","DOI":"10.1080\/1061186X.2018.1455839","article-title":"Tf ligand-receptor-mediated exenatide-Zn2+ complex oral-delivery system for penetration enhancement of exenatide","volume":"26","author":"Zhang","year":"2018","journal-title":"J. Drug Target."},{"key":"ref_229","doi-asserted-by":"crossref","first-page":"989","DOI":"10.2217\/nnm-2018-0322","article-title":"Oral delivery system for low molecular weight protamine-dextran-poly(lactic-co-glycolic acid) carrying exenatide to overcome the mucus barrier and improve intestinal targeting efficiency","volume":"14","author":"Song","year":"2019","journal-title":"Nanomedicine"},{"key":"ref_230","doi-asserted-by":"crossref","unstructured":"Ismail, R., Bocsik, A., Katona, G., Gr\u00f3f, I., Deli, M.A., and Cs\u00f3ka, I. (2019). Encapsulation in polymeric nanoparticles enhances the enzymatic stability and the permeability of the glp-1 analog, liraglutide, across a culture model of intestinal permeability. Pharmaceutics, 11.","DOI":"10.3390\/pharmaceutics11110599"},{"key":"ref_231","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1007\/s11095-019-2620-9","article-title":"Synthesis and Statistical Optimization of Poly (Lactic-Co-Glycolic Acid) Nanoparticles Encapsulating GLP1 Analog Designed for Oral Delivery","volume":"36","author":"Ismail","year":"2019","journal-title":"Pharm. Res."},{"key":"ref_232","doi-asserted-by":"crossref","first-page":"101513","DOI":"10.1016\/j.jddst.2020.101513","article-title":"Orally deliverable nanoformulation of liraglutide against type 2 diabetic rat model","volume":"56","author":"Senduran","year":"2020","journal-title":"J. Drug Deliv. Sci. Technol."},{"key":"ref_233","first-page":"653","article-title":"Mimicking natural cholesterol assimilation to elevate the oral delivery of liraglutide for type II diabetes therapy","volume":"17","author":"Wu","year":"2022","journal-title":"Asian J. Pharm. Sci."},{"key":"ref_234","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1080\/10717544.2021.2023704","article-title":"Orally administered intelligent self-ablating nanoparticles: A new approach to improve drug cellular uptake and intestinal absorption","volume":"29","author":"Liang","year":"2022","journal-title":"Drug Deliv."},{"key":"ref_235","doi-asserted-by":"crossref","first-page":"621","DOI":"10.1016\/j.jconrel.2024.01.015","article-title":"Nanoparticles targeting the intestinal Fc receptor enhance intestinal cellular trafficking of semaglutide","volume":"366","author":"Pinto","year":"2024","journal-title":"J. Control. Release"},{"key":"ref_236","doi-asserted-by":"crossref","first-page":"28406","DOI":"10.1021\/acsnano.4c11172","article-title":"Bioengineered Nanomedicines Targeting the Intestinal Fc Receptor Achieve the Improved Glucoregulatory Effect of Semaglutide in a Type 2 Diabetic Mice Model","volume":"18","author":"Pinto","year":"2024","journal-title":"ACS Nano"},{"key":"ref_237","doi-asserted-by":"crossref","first-page":"105437","DOI":"10.1016\/j.jddst.2024.105437","article-title":"Sulfobetaine modification of poly (D, L-lactide-co-glycolic acid) nanoparticles enhances mucus permeability and improves bioavailability of orally delivered liraglutide","volume":"93","author":"Zhao","year":"2024","journal-title":"J. Drug Deliv. Sci. Technol."},{"key":"ref_238","doi-asserted-by":"crossref","unstructured":"Uhl, P., Grundmann, C., Sauter, M., Storck, P., Tursch, A., \u00d6zbek, S., Leotta, K., Roth, R., Witzigmann, D., and Kulkarni, J.A. (2020). Coating of PLA-Nanoparticles with Cyclic, Arginine-Rich Cell Penetrating Peptides Enables Oral Delivery of Liraglutide. Nanomed. Nanotechnol. Biol. Med., 24.","DOI":"10.1016\/j.nano.2019.102132"},{"key":"ref_239","doi-asserted-by":"crossref","first-page":"1017","DOI":"10.1007\/s11095-014-1513-1","article-title":"The Glucose-Lowering Potential of Exenatide Delivered Orally via Goblet Cell- Targeting Nanoparticles","volume":"32","author":"Li","year":"2015","journal-title":"Pharm. Res."},{"key":"ref_240","doi-asserted-by":"crossref","first-page":"1899","DOI":"10.1021\/acs.molpharmaceut.9b01307","article-title":"Intelligent Escape System for the Oral Delivery of Liraglutide: A Perfect Match for Gastrointestinal Barriers","volume":"17","author":"Yin","year":"2020","journal-title":"Mol. Pharm."},{"key":"ref_241","doi-asserted-by":"crossref","first-page":"754","DOI":"10.1177\/0885328220947889","article-title":"Oral delivery of liraglutide-loaded Poly-N-(2-hydroxypropyl) methacrylamide\/chitosan nanoparticles: Preparation, characterization, and pharmacokinetics","volume":"35","author":"Shi","year":"2021","journal-title":"J. Biomater. Appl."},{"key":"ref_242","doi-asserted-by":"crossref","first-page":"122585","DOI":"10.1016\/j.ijpharm.2023.122585","article-title":"Fat fighting liraglutide based nano-formulation to reverse obesity: Design, development and animal trials","volume":"634","author":"Jakhar","year":"2023","journal-title":"Int. J. Pharm."},{"key":"ref_243","first-page":"4983","article-title":"A silica-based pH-sensitive nanomatrix system improves the oral absorption and efficacy of incretin hormone glucagon-like peptide-l","volume":"7","author":"Qu","year":"2012","journal-title":"Int. J. Nanomed."},{"key":"ref_244","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1016\/j.jconrel.2016.04.024","article-title":"Oral hypoglycaemic effect of GLP-1 and DPP4 inhibitor based nanocomposites in a diabetic animal model","volume":"232","author":"Shrestha","year":"2016","journal-title":"J. Control. Release"},{"key":"ref_245","doi-asserted-by":"crossref","first-page":"44354","DOI":"10.1021\/acsami.8b20821","article-title":"Microfluidic Nanoassembly of Bioengineered Chitosan-Modified FcRn-Targeted Porous Silicon Nanoparticles @ Hypromellose Acetate Succinate for Oral Delivery of Antidiabetic Peptides","volume":"10","author":"Martins","year":"2018","journal-title":"ACS Appl. Mater. Interfaces"},{"key":"ref_246","doi-asserted-by":"crossref","unstructured":"Abeer, M.M., Meka, A.K., Pujara, N., Kumeria, T., Strounina, E., Nunes, R., Costa, A., Sarmento, B., Hasnain, S.Z., and Ross, B.P. (2019). Rationally designed dendritic silica nanoparticles for oral delivery of exenatide. Pharmaceutics, 11.","DOI":"10.3390\/pharmaceutics11080418"},{"key":"ref_247","doi-asserted-by":"crossref","first-page":"603","DOI":"10.1039\/C7NR07736J","article-title":"The stimulation of GLP-1 secretion and delivery of GLP-1 agonists: Via nanostructured lipid carriers","volume":"10","author":"Shrestha","year":"2018","journal-title":"Nanoscale"},{"key":"ref_248","doi-asserted-by":"crossref","first-page":"911","DOI":"10.1136\/gutjnl-2019-319146","article-title":"Novel strategy for oral peptide delivery in incretin-based diabetes treatment","volume":"69","author":"Xu","year":"2020","journal-title":"Gut"},{"key":"ref_249","doi-asserted-by":"crossref","unstructured":"Xu, Y., De Keersmaecker, H., Braeckmans, K., De Smedt, S., Cani, P.D., Pr\u00e9at, V., and Beloqui, A. (2020). Targeted nanoparticles towards increased L cell stimulation as a strategy to improve oral peptide delivery in incretin-based diabetes treatment. Biomaterials, 255.","DOI":"10.1016\/j.biomaterials.2020.120209"},{"key":"ref_250","doi-asserted-by":"crossref","first-page":"2917","DOI":"10.1007\/s13346-024-01576-z","article-title":"Effects of semaglutide-loaded lipid nanocapsules on metabolic dysfunction-associated steatotic liver disease","volume":"14","author":"Domingues","year":"2024","journal-title":"Drug Deliv. Transl. Res."},{"key":"ref_251","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1016\/j.jconrel.2018.12.028","article-title":"Long-Term Oral Administration of Exendin-4 to Control Type 2 Diabetes in a Rat Model","volume":"294","author":"Suzuki","year":"2019","journal-title":"J. Control. Release"},{"key":"ref_252","doi-asserted-by":"crossref","unstructured":"Ding, R., Zhao, Z., He, J., Tao, Y., Zhang, H., Yuan, R., Sun, K., and Shi, Y. (2023). Preparation, Drug Distribution, and In Vivo Evaluation of the Safety of Protein Corona Liposomes for Liraglutide Delivery. Nanomaterials, 13.","DOI":"10.3390\/nano13030540"},{"key":"ref_253","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1208\/s12248-024-00971-1","article-title":"Design of Auto-Adaptive Drug Delivery System for Effective Delivery of Peptide Drugs to Overcoming Mucus and Epithelial Barriers","volume":"26","author":"Ding","year":"2024","journal-title":"AAPS J."},{"key":"ref_254","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1016\/j.jconrel.2018.03.018","article-title":"In vivo evaluation of an oral self-emulsifying drug delivery system (SEDDS) for exenatide","volume":"277","author":"Menzel","year":"2018","journal-title":"J. Control. Release"},{"key":"ref_255","doi-asserted-by":"crossref","first-page":"5032","DOI":"10.1021\/acsbiomaterials.0c00637","article-title":"The Effect of Counterions in Hydrophobic Ion Pairs on Oral Bioavailability of Exenatide","volume":"6","author":"Phan","year":"2020","journal-title":"ACS Biomater. Sci. Eng."},{"key":"ref_256","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1016\/j.ejpb.2020.04.025","article-title":"Hydrophobic ion pairing of a GLP-1 analogue for incorporating into lipid nanocarriers designed for oral delivery","volume":"152","author":"Ismail","year":"2020","journal-title":"Eur. J. Pharm. Biopharm."},{"key":"ref_257","doi-asserted-by":"crossref","first-page":"1809015","DOI":"10.1002\/adfm.201809015","article-title":"Phase-Changeable Nanoemulsions for Oral Delivery of a Therapeutic Peptide: Toward Targeting the Pancreas for Antidiabetic Treatments Using Lymphatic Transport","volume":"29","author":"Lin","year":"2019","journal-title":"Adv. Funct. Mater."},{"key":"ref_258","doi-asserted-by":"crossref","unstructured":"Han, Y., Liu, W., Chen, L., Xin, X., Wang, Q., Zhang, X., Jin, M., Gao, Z., and Huang, W. (2021). Effective oral delivery of Exenatide-Zn2+ complex through distal ileum-targeted double layers nanocarriers modified with deoxycholic acid and glycocholic acid in diabetes therapy. Biomaterials, 275.","DOI":"10.1016\/j.biomaterials.2021.120944"},{"key":"ref_259","doi-asserted-by":"crossref","first-page":"292","DOI":"10.1016\/j.xphs.2020.10.058","article-title":"Pre-Clinical Evaluation of a Modified Cyclodextrin-Based Nanoparticle for Intestinal Delivery of Liraglutide","volume":"110","author":"Presas","year":"2021","journal-title":"J. Pharm. Sci."},{"key":"ref_260","doi-asserted-by":"crossref","first-page":"e2102044","DOI":"10.1002\/adma.202102044","article-title":"A pH-Triggered Self-Unpacking Capsule Containing Zwitterionic Hydrogel-Coated MOF Nanoparticles for Efficient Oral Exendin-4 Delivery","volume":"33","author":"Zhou","year":"2021","journal-title":"Adv. Mater."},{"key":"ref_261","doi-asserted-by":"crossref","unstructured":"Bao, X., Qian, K., and Yao, P. (2020). Oral delivery of exenatide-loaded hybrid zein nanoparticles for stable blood glucose control and \u03b2-cell repair of type 2 diabetes mice. J. Nanobiotechnol., 18.","DOI":"10.1186\/s12951-020-00619-0"},{"key":"ref_262","doi-asserted-by":"crossref","unstructured":"Bao, X., Qian, K., Xu, M., Chen, Y., Wang, H., Pan, T., Wang, Z., Yao, P., and Lin, L. (2023). Intestinal epithelium penetration of liraglutide via cholic acid pre-complexation and zein\/rhamnolipids nanocomposite delivery. J. Nanobiotechnol., 21.","DOI":"10.1186\/s12951-022-01743-9"},{"key":"ref_263","doi-asserted-by":"crossref","first-page":"21091","DOI":"10.1021\/acsnano.4c02560","article-title":"Milk Exosome-Liposome Hybrid Vesicles with Self-Adapting Surface Properties Overcome the Sequential Absorption Barriers for Oral Delivery of Peptides","volume":"18","author":"Xiao","year":"2024","journal-title":"ACS Nano"},{"key":"ref_264","doi-asserted-by":"crossref","first-page":"3937","DOI":"10.2147\/IJN.S413515","article-title":"Fabrication and Evaluation of a pH-Responsive Nanocomposite-Based Colonic Delivery System for Improving the Oral Efficacy of Liraglutide","volume":"18","author":"Song","year":"2023","journal-title":"Int. J. Nanomed."},{"key":"ref_265","doi-asserted-by":"crossref","unstructured":"Kim, G.L., Song, J.G., and Han, H.K. (2024). Enhanced Oral Efficacy of Semaglutide via an Ionic Nanocomplex with Organometallic Phyllosilicate in Type 2 Diabetic Rats. Pharmaceutics, 16.","DOI":"10.3390\/pharmaceutics16070886"},{"key":"ref_266","doi-asserted-by":"crossref","first-page":"637","DOI":"10.1016\/j.jconrel.2024.12.039","article-title":"An oral liraglutide nanomicelle formulation conferring reduced insulin-resistance and long-term hypoglycemic and lipid metabolic benefits","volume":"378","author":"Subedi","year":"2025","journal-title":"J. Control. Release"},{"key":"ref_267","doi-asserted-by":"crossref","first-page":"1377","DOI":"10.3390\/polym3031377","article-title":"Poly Lactic-Co-Glycolic Acid (PLGA) as Biodegradable Controlled Drug Delivery Carrier","volume":"3","author":"Makadia","year":"2011","journal-title":"Polymers"},{"key":"ref_268","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1038\/s41551-019-0465-5","article-title":"Anionic Nanoparticles Enable the Oral Delivery of Proteins by Enhancing Intestinal Permeability","volume":"4","author":"Lamson","year":"2020","journal-title":"Nat. Biomed. Eng."},{"key":"ref_269","doi-asserted-by":"crossref","first-page":"753569","DOI":"10.1155\/2015\/753569","article-title":"Cytotoxicity and Biological Efficacy of Exendin-4-Encapsulated Solid Lipid Nanoparticles in INS-1 Cells","volume":"2015","author":"Jun","year":"2015","journal-title":"J. Nanomater."},{"key":"ref_270","doi-asserted-by":"crossref","first-page":"150","DOI":"10.34172\/apb.2020.021","article-title":"Nanostructured Lipid Carriers: A Groundbreaking Approach for Transdermal Drug Delivery","volume":"10","author":"Chauhan","year":"2020","journal-title":"Adv. Pharm. Bull."},{"key":"ref_271","doi-asserted-by":"crossref","first-page":"4222","DOI":"10.1021\/acs.molpharmaceut.6b00871","article-title":"A Mechanistic Study on Nanoparticle-Mediated Glucagon-Like Peptide-1 (GLP-1) Secretion from Enteroendocrine L Cells","volume":"13","author":"Beloqui","year":"2016","journal-title":"Mol. Pharm."},{"key":"ref_272","doi-asserted-by":"crossref","first-page":"228","DOI":"10.1016\/j.jconrel.2020.05.015","article-title":"Poly(L-Glutamic Acid)-Co-Poly(Ethylene Glycol) Block Copolymers for Protein Conjugation","volume":"324","author":"Maso","year":"2020","journal-title":"J. Control. Release"},{"key":"ref_273","doi-asserted-by":"crossref","first-page":"460","DOI":"10.1016\/j.ijbiomac.2018.08.078","article-title":"Development of Chitosan Coated Calcium-Alginate Nanocapsules for Oral Delivery of Liraglutide to Diabetic Patients","volume":"120","author":"Shamekhi","year":"2018","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_274","doi-asserted-by":"crossref","first-page":"1722","DOI":"10.1021\/la5047047","article-title":"Electrostatic Interaction on Loading of Therapeutic Peptide GLP-1 into Porous Silicon Nanoparticles","volume":"31","author":"Kaasalainen","year":"2015","journal-title":"Langmuir"},{"key":"ref_275","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1021\/acs.molpharmaceut.7b00742","article-title":"Size Effect on Lipid Nanocapsule-Mediated GLP-1 Secretion from Enteroendocrine L Cells","volume":"15","author":"Xu","year":"2018","journal-title":"Mol. Pharm."},{"key":"ref_276","doi-asserted-by":"crossref","first-page":"eadq9909","DOI":"10.1126\/sciadv.adq9909","article-title":"Smart control lipid-based nanocarriers for fine-tuning gut hormone secretion","volume":"10","author":"Xu","year":"2024","journal-title":"Sci. Adv."},{"key":"ref_277","doi-asserted-by":"crossref","first-page":"2146","DOI":"10.1007\/s13346-024-01729-0","article-title":"Design of self-emulsifying oral delivery systems for semaglutide: Reverse micelles versus hydrophobic ion pairs","volume":"15","author":"Sandmeier","year":"2024","journal-title":"Drug Deliv. Transl. Res."},{"key":"ref_278","doi-asserted-by":"crossref","first-page":"e1800202","DOI":"10.1002\/adma.201800202","article-title":"Metal\u2013Organic Framework Nanoparticles","volume":"30","author":"Wang","year":"2018","journal-title":"Adv. Mater."},{"key":"ref_279","doi-asserted-by":"crossref","first-page":"122255","DOI":"10.1016\/j.ijpharm.2022.122255","article-title":"Oral administration of zein-based nanoparticles reduces glycemia and improves glucose tolerance in rats","volume":"628","author":"Reboredo","year":"2022","journal-title":"Int. J. Pharm."},{"key":"ref_280","doi-asserted-by":"crossref","first-page":"1072","DOI":"10.2174\/1389201022666210820114236","article-title":"Construction and Evaluation of Liraglutide Delivery System based on Milk Exosomes: A New Idea for Oral Peptide Delivery","volume":"23","author":"Shi","year":"2022","journal-title":"Curr. Pharm. Biotechnol."},{"key":"ref_281","unstructured":"Golden, J. (2025, July 03). The GLP-1 Boom: Challenges, Trends, and CapEx Strategies for Manufacturers. Available online: https:\/\/www.crbgroup.com\/insights\/glp-1-manufacturing."},{"key":"ref_282","doi-asserted-by":"crossref","first-page":"194","DOI":"10.1021\/acsnanoscienceau.3c00035","article-title":"Enhancing the Therapeutic Efficacy of GLP-1 for Hyperglycemia Treatment: Overcoming Barriers of Oral Gene Therapy with Taurocholic Acid-Conjugated Protamine Sulfate and Calcium Phosphate","volume":"4","author":"Shahriar","year":"2024","journal-title":"ACS Nanosci. Au"},{"key":"ref_283","doi-asserted-by":"crossref","first-page":"802","DOI":"10.1089\/hum.2017.180","article-title":"Therapeutic Potential of Lentivirus-Mediated Glucagon-Like Peptide-1 Gene Therapy for Diabetes","volume":"29","author":"Tasyurek","year":"2018","journal-title":"Hum. Gene Ther."},{"key":"ref_284","doi-asserted-by":"crossref","first-page":"340632","DOI":"10.5402\/2012\/340632","article-title":"Polymer-Based Delivery of Glucagon-Like Peptide-1 for the Treatment of Diabetes","volume":"2012","author":"Kim","year":"2012","journal-title":"ISRN Endocrinol."},{"key":"ref_285","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1038\/s41576-021-00439-4","article-title":"Drug delivery systems for RNA therapeutics","volume":"23","author":"Paunovska","year":"2022","journal-title":"Nat. Rev. Genet."},{"key":"ref_286","doi-asserted-by":"crossref","first-page":"1713","DOI":"10.1056\/NEJMoa1706198","article-title":"Single-Dose Gene-Replacement Therapy for Spinal Muscular Atrophy","volume":"377","author":"Mendell","year":"2017","journal-title":"N. Engl. J. Med."},{"key":"ref_287","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1056\/NEJMoa1908490","article-title":"Multiyear Follow-up of AAV5-hFVIII-SQ Gene Therapy for Hemophilia A","volume":"382","author":"Pasi","year":"2020","journal-title":"N. Engl. J. Med."},{"key":"ref_288","doi-asserted-by":"crossref","first-page":"252","DOI":"10.1056\/NEJMoa2031054","article-title":"CRISPR-Cas9 Gene Editing for Sickle Cell Disease and \u03b2-Thalassemia","volume":"384","author":"Frangoul","year":"2021","journal-title":"N. Engl. J. Med."},{"key":"ref_289","doi-asserted-by":"crossref","first-page":"2002","DOI":"10.1056\/NEJMoa2027675","article-title":"Autologous Ex Vivo Lentiviral Gene Therapy for Adenosine Deaminase Deficiency","volume":"384","author":"Kohn","year":"2021","journal-title":"N. Engl. J. Med."},{"key":"ref_290","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1089\/hgtb.2017.036","article-title":"Improving miRNA Delivery by Optimizing miRNA Expression Cassettes in Diverse Virus Vectors","volume":"28","author":"Liu","year":"2017","journal-title":"Hum. Gene Ther. Methods"},{"key":"ref_291","doi-asserted-by":"crossref","first-page":"305","DOI":"10.1016\/j.jconrel.2017.08.035","article-title":"Oral delivery of a therapeutic gene encoding glucagon-like peptide 1 to treat high fat diet-induced diabetes","volume":"268","author":"Nurunnabi","year":"2017","journal-title":"J. Control. Release"},{"key":"ref_292","doi-asserted-by":"crossref","first-page":"29593","DOI":"10.1021\/acsami.9b10294","article-title":"Surface Coating Approach to Overcome Mucosal Entrapment of DNA Nanoparticles for Oral Gene Delivery of Glucagon-like Peptide 1","volume":"11","author":"Nie","year":"2019","journal-title":"ACS Appl. Mater. Interfaces"},{"key":"ref_293","doi-asserted-by":"crossref","first-page":"38925","DOI":"10.1021\/acsami.0c09814","article-title":"Oral GLP1 Gene Delivery by an Antibody-Guided Nanomaterial to Treat Type 2 Diabetes Mellitus","volume":"12","author":"Hasan","year":"2020","journal-title":"ACS Appl. Mater. Interfaces"},{"key":"ref_294","doi-asserted-by":"crossref","unstructured":"Zeng, Y., Wu, Y., Zhang, Q., and Xiao, X. (2024). Crosstalk between glucagon-like peptide 1 and gut microbiota in metabolic diseases. mBio, 15.","DOI":"10.1128\/mbio.02032-23"},{"key":"ref_295","doi-asserted-by":"crossref","first-page":"164","DOI":"10.1038\/s41575-023-00867-z","article-title":"Gut microbiota in overweight and obesity: Crosstalk with adipose tissue","volume":"21","author":"Cani","year":"2023","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"ref_296","doi-asserted-by":"crossref","unstructured":"Abdalqadir, N., and Adeli, K. (2022). GLP-1 and GLP-2 Orchestrate Intestine Integrity, Gut Microbiota, and Immune System Crosstalk. Microorganisms, 10.","DOI":"10.3390\/microorganisms10102061"},{"key":"ref_297","doi-asserted-by":"crossref","first-page":"1397","DOI":"10.1038\/s42255-024-01072-1","article-title":"Ketogenic diet-induced bile acids protect against obesity through reduced calorie absorption","volume":"6","author":"Li","year":"2024","journal-title":"Nat. Metab."},{"key":"ref_298","doi-asserted-by":"crossref","first-page":"671","DOI":"10.1038\/s41579-024-01068-4","article-title":"The interplay between diet and the gut microbiome: Implications for health and disease","volume":"22","author":"Ross","year":"2024","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_299","doi-asserted-by":"crossref","first-page":"e436","DOI":"10.1002\/edm2.436","article-title":"Human gut microbiome: Therapeutic opportunities for metabolic syndrome-Hype or hope?","volume":"7","author":"Horvath","year":"2023","journal-title":"Endocrinol. Diabetes Metab."},{"key":"ref_300","first-page":"29","article-title":"Advanced microbiome therapeutics as a novel modality for oral delivery of peptides to manage metabolic diseases","volume":"36","author":"Hedin","year":"2024","journal-title":"Trends Endocrinol. Metab."},{"key":"ref_301","doi-asserted-by":"crossref","first-page":"460","DOI":"10.1016\/S2468-1253(23)00357-6","article-title":"Fine-tuning the gut ecosystem: The current landscape and outlook of artificial microbiome therapeutics","volume":"9","author":"Porcari","year":"2024","journal-title":"Lancet Gastroenterol. Hepatol."},{"key":"ref_302","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1002\/oby.22700","article-title":"Genetically Engineered Escherichia coli Nissle 1917 Secreting GLP-1 Analog Exhibits Potential Antiobesity Effect in High-Fat Diet-Induced Obesity Mice","volume":"28","author":"Ma","year":"2020","journal-title":"Obesity"},{"key":"ref_303","doi-asserted-by":"crossref","first-page":"3433","DOI":"10.1021\/acssynbio.3c00455","article-title":"Cold Exposure and Oral Delivery of GLP-1R Agonists by an Engineered Probiotic Yeast Strain Have Antiobesity Effects in Mice","volume":"12","author":"Hedin","year":"2023","journal-title":"ACS Synth. Biol."},{"key":"ref_304","doi-asserted-by":"crossref","unstructured":"Lou, J., Duan, H., Qin, Q., Teng, Z., Gan, F., Zhou, X., and Zhou, X. (2023). Advances in Oral Drug Delivery Systems: Challenges and Opportunities. Pharmaceutics, 15.","DOI":"10.3390\/pharmaceutics15020484"},{"key":"ref_305","doi-asserted-by":"crossref","first-page":"212","DOI":"10.1111\/nbu.12334","article-title":"Probiotics for human use","volume":"43","author":"Sanders","year":"2018","journal-title":"Nutr. Bull."},{"key":"ref_306","doi-asserted-by":"crossref","first-page":"e0012723","DOI":"10.1128\/jb.00127-23","article-title":"Genetic Engineering of Resident Bacteria in the Gut Microbiome","volume":"205","author":"Arnold","year":"2023","journal-title":"J. Bacteriol."},{"key":"ref_307","doi-asserted-by":"crossref","first-page":"3404","DOI":"10.1007\/s11095-014-1430-3","article-title":"Oral delivery of glucagon like peptide-1 by a recombinant Lactococcus lactis","volume":"31","author":"Agarwal","year":"2014","journal-title":"Pharm. Res."},{"key":"ref_308","doi-asserted-by":"crossref","first-page":"2829","DOI":"10.1007\/s12274-022-4963-5","article-title":"A micro-nano optogenetic system based on probiotics for in situ host metabolism regulation","volume":"16","author":"Zhang","year":"2022","journal-title":"Nano Res."},{"key":"ref_309","doi-asserted-by":"crossref","unstructured":"Zeng, Z., Yu, R., Zuo, F., Zhang, B., Peng, D., Ma, H., and Chen, S. (2016). Heterologous Expression and Delivery of Biologically Active Exendin-4 by Lactobacillus paracasei L14. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0165130"},{"key":"ref_310","doi-asserted-by":"crossref","first-page":"725","DOI":"10.1016\/j.molmet.2016.06.006","article-title":"Microbially produced glucagon-like peptide 1 improves glucose tolerance in mice","volume":"5","author":"Arora","year":"2016","journal-title":"Mol. Metab."},{"key":"ref_311","doi-asserted-by":"crossref","unstructured":"Wang, Q., Guo, H., Mao, W., Qian, X., and Liu, Y. (2023). The Oral Delivery System of Modified GLP-1 by Probiotics for T2DM. Pharmaceutics, 15.","DOI":"10.3390\/pharmaceutics15041202"},{"key":"ref_312","doi-asserted-by":"crossref","first-page":"e2303958","DOI":"10.1002\/adhm.202303958","article-title":"Biochemotaxis-Oriented Engineering Bacteria Expressing GLP-1 Enhance Diabetes Therapy by Regulating the Balance of Immune","volume":"13","author":"Wang","year":"2024","journal-title":"Adv. Healthc. Mater."},{"key":"ref_313","doi-asserted-by":"crossref","first-page":"272","DOI":"10.1016\/j.synbio.2021.09.009","article-title":"Antidiabetic effect of an engineered bacterium Lactobacillus plantarum-pMG36e -GLP-1 in monkey model","volume":"6","author":"Luo","year":"2021","journal-title":"Synth. Syst. Biotechnol."},{"key":"ref_314","doi-asserted-by":"crossref","first-page":"1240","DOI":"10.1007\/s12602-023-10111-4","article-title":"Changes in the Human Gut Microbiome Caused by the Short-Term Impact of Lactic Acid Bacteria Consumption in Healthy People","volume":"16","author":"Gryaznova","year":"2024","journal-title":"Probiotics Antimicrob. Proteins"},{"key":"ref_315","doi-asserted-by":"crossref","first-page":"6049","DOI":"10.1021\/acsnano.1c11536","article-title":"Light-Sensitive Lactococcus lactis for Microbe-Gut-Brain Axis Regulating via Upconversion Optogenetic Micro-Nano System","volume":"16","author":"Pan","year":"2022","journal-title":"ACS Nano"},{"key":"ref_316","doi-asserted-by":"crossref","first-page":"557","DOI":"10.1111\/bph.15638","article-title":"Brain GLP-1 and the regulation of food intake: GLP-1 action in the brain and its implications for GLP-1 receptor agonists in obesity treatment","volume":"179","author":"Trapp","year":"2022","journal-title":"Br. J. Pharmacol."},{"key":"ref_317","doi-asserted-by":"crossref","first-page":"1011","DOI":"10.1038\/d41586-024-01352-6","article-title":"Dual-action obesity drug rewires brain circuits for appetite","volume":"629","author":"Cook","year":"2024","journal-title":"Nature"},{"key":"ref_318","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1007\/s12038-018-9831-9","article-title":"Construction of a dietary-cure Saccharomyces cerevisiae expressing long-acting glucagon-like peptide-1 and investigation of its hypoglycemic activity in type 2 diabetes mellitus mouse model","volume":"44","author":"Jiang","year":"2019","journal-title":"J. Biosci."},{"key":"ref_319","doi-asserted-by":"crossref","first-page":"1077","DOI":"10.1056\/NEJMoa2500969","article-title":"Oral Semaglutide at a Dose of 25 mg in Adults with Overweight or Obesity","volume":"393","author":"Wharton","year":"2025","journal-title":"N. Engl. J. Med."},{"key":"ref_320","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1016\/j.euroneuro.2024.02.003","article-title":"Exploring the association between suicidal thoughts, self-injury, and GLP-1 receptor agonists in weight loss treatments: Insights from pharmacovigilance measures and unmasking analysis","volume":"82","author":"Guirguis","year":"2024","journal-title":"Eur. Neuropsychopharmacol."},{"key":"ref_321","doi-asserted-by":"crossref","first-page":"e99","DOI":"10.1192\/j.eurpsy.2023.2474","article-title":"Postmarket safety profile of suicide\/self-injury for GLP-1 receptor agonist: A real-world pharmacovigilance analysis","volume":"66","author":"Chen","year":"2023","journal-title":"Eur. Psychiatry"},{"key":"ref_322","doi-asserted-by":"crossref","unstructured":"Chiappini, S., Vickers-Smith, R., Harris, D., Papanti Pelletier, G.D., Corkery, J.M., Guirguis, A., Martinotti, G., Sensi, S.L., and Schifano, F. (2023). Is There a Risk for Semaglutide Misuse? Focus on the Food and Drug Administration\u2019s FDA Adverse Events Reporting System (FAERS) Pharmacovigilance Dataset. Pharmaceuticals, 16.","DOI":"10.20944\/preprints202306.0611.v1"},{"key":"ref_323","doi-asserted-by":"crossref","first-page":"e13709","DOI":"10.1111\/obr.13709","article-title":"Highway to the danger zone? A cautionary account that GLP-1 receptor agonists may be too effective for unmonitored weight loss","volume":"25","author":"Richards","year":"2024","journal-title":"Obes. Rev."},{"key":"ref_324","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1093\/asj\/sjad211","article-title":"Public Interest in the Off-Label Use of Glucagon-like Peptide 1 Agonists (Ozempic) for Cosmetic Weight Loss: A Google Trends Analysis","volume":"44","author":"Han","year":"2024","journal-title":"Aesthet. Surg. J."},{"key":"ref_325","doi-asserted-by":"crossref","unstructured":"Arillotta, D., Floresta, G., Guirguis, A., Corkery, J.M., Catalani, V., Martinotti, G., Sensi, S.L., and Schifano, F. (2023). GLP-1 Receptor Agonists and Related Mental Health Issues; Insights from a Range of Social Media Platforms Using a Mixed-Methods Approach. Brain Sci., 13.","DOI":"10.3390\/brainsci13111503"},{"key":"ref_326","doi-asserted-by":"crossref","first-page":"1915","DOI":"10.1080\/14656566.2023.2271389","article-title":"Exploring the nexus of binge eating disorder (BED), New Psychoactive Substances (NPS), and misuse of pharmaceuticals: Charting a path forward","volume":"24","author":"Chiappini","year":"2023","journal-title":"Expert Opin. Pharmacother."},{"key":"ref_327","doi-asserted-by":"crossref","first-page":"286","DOI":"10.1002\/eat.24109","article-title":"Use of glucagon-like peptide-1 receptor agonists in eating disorder populations","volume":"57","author":"Bartel","year":"2024","journal-title":"Int. J. Eat. Disord."},{"key":"ref_328","doi-asserted-by":"crossref","first-page":"536","DOI":"10.1186\/s12967-024-05322-4","article-title":"Current perspectives in obesity management: Unraveling the impact of different therapy approach in real life obesity care","volume":"22","author":"Cammarata","year":"2024","journal-title":"J. Transl. Med."}],"container-title":["Pharmaceutics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4923\/17\/12\/1596\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,12,11]],"date-time":"2025-12-11T08:45:00Z","timestamp":1765442700000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4923\/17\/12\/1596"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,12,10]]},"references-count":328,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2025,12]]}},"alternative-id":["pharmaceutics17121596"],"URL":"https:\/\/doi.org\/10.3390\/pharmaceutics17121596","relation":{},"ISSN":["1999-4923"],"issn-type":[{"value":"1999-4923","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,12,10]]}}}