Review Article: GLP ‐1 Receptor Agonists and Glucagon/ GIP / GLP ‐1 Receptor Dual or Triple Agonists—Mechanism of Action and Emerging Therapeutic Landscape in MASLD
Open accessAbstract
Background: Metabolic dysfunction‐associated steatotic liver disease (MASLD) is primarily managed through diet and lifestyle modifications. However, these behavioural interventions alone may not achieve disease regression or remission, and maintaining long‐term adherence is challenging. Incretin mimetics and other gastrointestinal hormones targeting the pleiotropic pathophysiological pathways underlying MASLD have now emerged as promising disease‐modifying therapies. Aims: This is a comprehensive review summarising the role of glucagon‐like peptide‐1 (GLP‐1) receptor agonists and glucagon/glucose‐dependent insulinotropic polypeptide (GIP)/GLP‐1 receptor dual or triple agonists in the treatment of metabolic dysfunction‐associated steatohepatitis (MASH). Methods: Only clinical trials with endpoints assessed by liver histology were included for a robust evaluation of therapeutic efficacy. Results: Recent evidence from phase 2 clinical trials for MASH demonstrated that pharmacological agents based on GLP‐1 receptor agonism are effective in improving disease activity. Additionally, tirzepatide and survodutide showed potential clinical benefits in reducing fibrosis. Other cardiometabolic benefits observed include weight loss and improvements in glycaemic control and lipid profile. Adherence to treatment may be limited by gastrointestinal side effects, though they were found to be generally mild to moderate in severity. An interim analysis of the semaglutide phase 3 trial confirmed its efficacy in improving steatohepatitis and demonstrated its potential to improve fibrosis. Conclusions: GLP‐1 receptor agonists, alone or in combination with GIP and/or glucagon receptor agonists, represent promising, effective pharmacotherapies for the treatment of MASLD/MASH. Larger and longer‐duration clinical trials are needed to further evaluate the efficacy and safety of GIP receptor and glucagon receptor agonism.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Liraglutide and Cardiovascular Outcomes in Type 2 Diabetes
Marso, S. P., Daniels, G. H., Brown-Frandsen, K., Kristensen, P., Mann, J. F. E., Nauck, M. A., Nissen, S. E., Pocock, S., Poulter, N. R., Ravn, L. S., et al. (2016) · New England Journal of Medicine · doi:10.1056/nejmoa1603827 · Cited by 7,629 · see citing works
Semaglutide and Cardiovascular Outcomes in Patients with Type 2 Diabetes
Marso, S. P., Bain, S. C., Consoli, A., Eliaschewitz, F. G., Jódar, E., Leiter, L. A., Lingvay, I., Rosenstock, J., Seufert, J., Warren, M. L., et al. (2016) · New England Journal of Medicine · doi:10.1056/nejmoa1607141 · Cited by 6,900 · see citing works
Once-Weekly Semaglutide in Adults with Overweight or Obesity
Wilding, J. P. H., Batterham, R. L., Calanna, S., Davies, M., Van Gaal, L. F., Lingvay, I., McGowan, B. M., Rosenstock, J., Tran, M. T. D., Wadden, T. A., et al. (2021) · New England Journal of Medicine · doi:10.1056/nejmoa2032183 · Cited by 5,205 · see citing works
Tirzepatide Once Weekly for the Treatment of Obesity
Jastreboff, A. M., Aronne, L. J., Ahmad, N. N., Wharton, S., Connery, L., Alves, B., Kiyosue, A., Zhang, S., Liu, B., Bunck, M. C., et al. (2022) · New England Journal of Medicine · doi:10.1056/nejmoa2206038 · Cited by 3,838 · see citing works
Biology of Incretins: GLP-1 and GIP
Baggio, L. L., & Drucker, D. J. (2007) · Gastroenterology · doi:10.1053/j.gastro.2007.03.054 · Cited by 3,639 · see citing works
Semaglutide and Cardiovascular Outcomes in Obesity without Diabetes
Lincoff, A. M., Brown-Frandsen, K., Colhoun, H. M., Deanfield, J., Emerson, S. S., Esbjerg, S., Hardt-Lindberg, S., Hovingh, G. K., Kahn, S. E., Kushner, R. F., et al. (2023) · New England Journal of Medicine · doi:10.1056/nejmoa2307563 · Cited by 3,236 · see citing works
Gerstein, H. C., Colhoun, H. M., Dagenais, G. R., Diaz, R., Lakshmanan, M., Pais, P., Probstfield, J., Riesmeyer, J. S., Riddle, M. C., Rydén, L., et al. (2019) · The Lancet · doi:10.1016/s0140-6736(19)31149-3 · Cited by 3,163 · see citing works
A Randomized, Controlled Trial of 3.0 mg of Liraglutide in Weight Management
Pi-Sunyer, X., Astrup, A., Fujioka, K., Greenway, F., Halpern, A., Krempf, M., Lau, D. C. W., le Roux, C. W., Violante Ortiz, R., Jensen, C. B., et al. (2015) · New England Journal of Medicine · doi:10.1056/nejmoa1411892 · Cited by 2,724 · see citing works
The biology of incretin hormones
Drucker, D. J. (2006) · Cell Metabolism · doi:10.1016/j.cmet.2006.01.004 · Cited by 2,210 · see citing works
Armstrong, M. J., Gaunt, P., Aithal, G. P., Barton, D., Hull, D., Parker, R., Hazlehurst, J. M., Guo, K., Abouda, G., Aldersley, M. A., et al. (2016) · The Lancet · doi:10.1016/s0140-6736(15)00803-x · Cited by 2,203 · see citing works
Mechanisms of Action and Therapeutic Application of Glucagon-like Peptide-1
Drucker, D. J. (2018) · Cell Metabolism · doi:10.1016/j.cmet.2018.03.001 · Cited by 2,170 · see citing works
A phase 3, randomized, controlled trial of resmetirom in NASH with liver fibrosis
Harrison, S. A., Bedossa, P., Guy, C. D., Schattenberg, J. M., Loomba, R., Taub, R., Labriola, D., Moussa, S. E., Neff, G. W., Rinella, M. E., et al. (2024) · New England Journal of Medicine · doi:10.1056/nejmoa2309000 · Cited by 2,084 · see citing works
Self-citationA Placebo-controlled trial of subcutaneous semaglutide in nonalcoholic steatohepatitis
Newsome, P. N., Buchholtz, K., Cusi, K., Linder, M., Okanoue, T., Ratziu, V., Sanyal, A. J., Sejling, A.-S., & Harrison, S. A. (2021) · New England Journal of Medicine · doi:10.1056/nejmoa2028395 · Cited by 2,039 · see citing works
Dulai, P. S., Singh, S., Patel, J., Soni, M., Prokop, L. J., Younossi, Z., Sebastiani, G., Ekstedt, M., Hagstrom, H., Nasr, P., et al. (2017) · Hepatology · doi:10.1002/hep.29085 · Cited by 1,965 · see citing works
Self-citationEffects of Semaglutide on Chronic Kidney Disease in Patients with Type 2 Diabetes.
Perkovic, V., Tuttle, K. R., Rossing, P., Mahaffey, K. W., Mann, J. F. E., Bakris, G., Baeres, F. M. M., Idorn, T., Bosch-Traberg, H., Lausvig, N. L., et al. (2024) · New England Journal of Medicine · doi:10.1056/nejmoa2403347 · Cited by 1,849 · see citing works
Semaglutide in Patients with Heart Failure with Preserved Ejection Fraction and Obesity
Kosiborod, M. N., Abildstrøm, S. Z., Borlaug, B. A., Butler, J., Rasmussen, S., Davies, M., Hovingh, G. K., Kitzman, D. W., Lindegaard, M. L., Møller, D. V., et al. (2023) · New England Journal of Medicine · doi:10.1056/nejmoa2306963 · Cited by 1,669 · see citing works
Davies, M., Færch, L., Jeppesen, O. K., Pakseresht, A., Pedersen, S. D., Perreault, L., Rosenstock, J., Shimomura, I., Viljoen, A., Wadden, T. A., et al. (2021) · The Lancet · doi:10.1016/s0140-6736(21)00213-0 · Cited by 1,419 · see citing works
Adipogenesis and metabolic health
Ghaben, A. L., & Scherer, P. E. (2019) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-018-0093-z · Cited by 1,395 · see citing works
Triple-Hormone-Receptor Agonist Retatrutide for Obesity — A Phase 2 Trial
Jastreboff, A. M., Kaplan, L. M., Frías, J. P., Wu, Q., Du, Y., Gurbuz, S., Coskun, T., Haupt, A., Milicevic, Z., & Hartman, M. L. (2023) · New England Journal of Medicine · doi:10.1056/nejmoa2301972 · Cited by 1,174 · see citing works
Regulation of hepatic glucose metabolism in health and disease
Petersen, M. C., Vatner, D. F., & Shulman, G. I. (2017) · Nature Reviews Endocrinology · doi:10.1038/nrendo.2017.80 · Cited by 1,131 · see citing works
Phase 3 Trial of Semaglutide in Metabolic Dysfunction–Associated Steatohepatitis
Sanyal, A. J., Newsome, P. N., Kliers, I., Østergaard, L. H., Long, M. T., Kjær, M. S., Cali, A. M. G., Bugianesi, E., Rinella, M. E., Roden, M., et al. (2025) · New England Journal of Medicine · doi:10.1056/nejmoa2413258 · Cited by 1,115 · see citing works
Wadden, T. A., Bailey, T. S., Billings, L. K., Davies, M., Frias, J. P., Koroleva, A., Lingvay, I., O’Neil, P. M., Rubino, D. M., Skovgaard, D., et al. (2021) · JAMA · doi:10.1001/jama.2021.1831 · Cited by 1,114 · see citing works
Tirzepatide for metabolic dysfunction-associated steatohepatitis with liver fibrosis
Loomba, R., Hartman, M. L., Lawitz, E. J., Vuppalanchi, R., Boursier, J., Bugianesi, E., Yoneda, M., Behling, C., Cummings, O. W., Tang, Y., et al. (2024) · New England Journal of Medicine · doi:10.1056/nejmoa2401943 · Cited by 1,005 · see citing works
Self-citationIncretin hormones: Their role in health and disease
Nauck, M. A., & Meier, J. J. (2018) · Diabetes, Obesity and Metabolism · doi:10.1111/dom.13129 · Cited by 950 · see citing works
The Role of Insulin Resistance in Nonalcoholic Fatty Liver Disease
Utzschneider, K. M., & Kahn, S. E. (2006) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2006-0587 · Cited by 858 · see citing works
Semaglutide in Patients with Obesity-Related Heart Failure and Type 2 Diabetes
Kosiborod, M. N., Petrie, M. C., Borlaug, B. A., Butler, J., Davies, M. J., Hovingh, G. K., Kitzman, D. W., Møller, D. V., Treppendahl, M. B., Verma, S., et al. (2024) · New England Journal of Medicine · doi:10.1056/nejmoa2313917 · Cited by 758 · see citing works
GIP and GLP-1, the two incretin hormones: Similarities and differences
Seino, Y., Fukushima, M., & Yabe, D. (2010) · Journal of Diabetes Investigation · doi:10.1111/j.2040-1124.2010.00022.x · Cited by 746 · see citing works
Margulies, K. B., Hernandez, A. F., Redfield, M. M., Givertz, M. M., Oliveira, G. H., Cole, R., Mann, D. L., Whellan, D. J., Kiernan, M. S., Felker, G. M., et al. (2016) · JAMA · doi:10.1001/jama.2016.10260 · Cited by 706 · see citing works
Unimolecular Dual Incretins Maximize Metabolic Benefits in Rodents, Monkeys, and Humans
Finan, B., Ma, T., Ottaway, N., Müller, T. D., Habegger, K. M., Heppner, K. M., Kirchner, H., Holland, J., Hembree, J., Raver, C., et al. (2013) · Science Translational Medicine · doi:10.1126/scitranslmed.3007218 · Cited by 696 · see citing works
A rationally designed monomeric peptide triagonist corrects obesity and diabetes in rodents
Finan, B., Yang, B., Ottaway, N., Smiley, D. L., Ma, T., Clemmensen, C., Chabenne, J., Zhang, L., Habegger, K. M., Fischer, K., et al. (2015) · Nature Medicine · doi:10.1038/nm.3761 · Cited by 645 · see citing works
Sensory neurons that detect stretch and nutrients in the digestive system
Williams, E. K., Chang, R. B., Strochlic, D. E., Umans, B. D., Lowell, B. B., & Liberles, S. D. (2016) · Cell · doi:10.1016/j.cell.2016.05.011 · Cited by 645 · see citing works
Jorsal, A., Kistorp, C., Holmager, P., Tougaard, R. S., Nielsen, R., Hänselmann, A., Nilsson, B., Møller, J. E., Hjort, J., Rasmussen, J., et al. (2017) · European Journal of Heart Failure · doi:10.1002/ejhf.657 · Cited by 592 · see citing works
The Multiple Actions of GLP-1 on the Process of Glucose-Stimulated Insulin Secretion
MacDonald, P. E., El-kholy, W., Riedel, M. J., Salapatek, A. M. F., Light, P. E., & Wheeler, M. B. (2002) · Diabetes · doi:10.2337/diabetes.51.2007.s434 · Cited by 590 · see citing works
on behalf of the SCALE study group, Blackman, A., Foster, G. D., Zammit, G., Rosenberg, R., Aronne, L., Wadden, T., Claudius, B., Jensen, C. B., & Mignot, E. (2016) · International Journal of Obesity · doi:10.1038/ijo.2016.52 · Cited by 583 · see citing works
Loomba, R., Abdelmalek, M. F., Armstrong, M. J., Jara, M., Kjær, M. S., Krarup, N., Lawitz, E., Ratziu, V., Sanyal, A. J., Schattenberg, J. M., et al. (2023) · The Lancet Gastroenterology & Hepatology · doi:10.1016/s2468-1253(23)00068-7 · Cited by 533 · see citing works
Self-citationA Phase 2 Randomized Trial of Survodutide in MASH and Fibrosis
Sanyal, A. J., Bedossa, P., Fraessdorf, M., Neff, G. W., Lawitz, E., Bugianesi, E., Anstee, Q. M., Hussain, S. A., Newsome, P. N., Ratziu, V., et al. (2024) · New England Journal of Medicine · doi:10.1056/nejmoa2401755 · Cited by 528 · see citing works
Alhadeff, A. L., Rupprecht, L. E., & Hayes, M. R. (2012) · Endocrinology · doi:10.1210/en.2011-1443 · Cited by 515 · see citing works
Gastaldelli, A., Cusi, K., Fernández Landó, L., Bray, R., Brouwers, B., & Rodríguez, Á. (2022) · The Lancet Diabetes & Endocrinology · doi:10.1016/s2213-8587(22)00070-5 · Cited by 513 · see citing works
Anti-Inflammatory Effects of GLP-1-Based Therapies beyond Glucose Control
Lee, Y.-S., & Jun, H.-S. (2016) · Mediators of Inflammation · doi:10.1155/2016/3094642 · Cited by 503 · see citing works
GLP-1 Receptor Agonists: Beyond Their Pancreatic Effects
Zhao, X., Wang, M., Wen, Z., Lu, Z., Cui, L., Fu, C., Xue, H., Liu, Y., & Zhang, Y. (2021) · Frontiers in Endocrinology · doi:10.3389/fendo.2021.721135 · Cited by 463 · see citing works
Glucagon-like peptide 1 decreases lipotoxicity in non-alcoholic steatohepatitis
Armstrong, M. J., Hull, D., Guo, K., Barton, D., Hazlehurst, J. M., Gathercole, L. L., Nasiri, M., Yu, J., Gough, S. C., Newsome, P. N., et al. (2016) · Journal of Hepatology · doi:10.1016/j.jhep.2015.08.038 · Cited by 456 · see citing works
Ileal brake: a sensible food target for appetite control. A review
Maljaars, P. W. J., Peters, H. P. F., Mela, D. J., & Masclee, A. A. M. (2008) · Physiology & Behavior · doi:10.1016/j.physbeh.2008.07.018 · Cited by 451 · see citing works
How May GIP Enhance the Therapeutic Efficacy of GLP-1?
Samms, R. J., Coghlan, M. P., & Sloop, K. W. (2020) · Trends in Endocrinology & Metabolism · doi:10.1016/j.tem.2020.02.006 · Cited by 419 · see citing works
Nauck, M. A., Quast, D. R., Wefers, J., & Pfeiffer, A. F. H. (2021) · Diabetes, Obesity and Metabolism · doi:10.1111/dom.14496 · Cited by 388 · see citing works
Downregulation of GLP-1 and GIP Receptor Expression by Hyperglycemia
Xu, G., Kaneto, H., Laybutt, D. R., Duvivier-Kali, V. F., Trivedi, N., Suzuma, K., King, G. L., Weir, G. C., & Bonner‐Weir, S. (2007) · Diabetes · doi:10.2337/db06-1033 · Cited by 379 · see citing works
Neurobiology of Feeding and Energy Expenditure
Gao, Q., & Horvath, T. L. (2007) · Annual Review of Neuroscience · doi:10.1146/annurev.neuro.30.051606.094324 · Cited by 346 · see citing works
Metabolic dysfunction-associated steatotic liver disease in adults
Huang, D. Q., Wong, V. W., Rinella, M. E., Boursier, J., Lazarus, J. V., Yki‐Järvinen, H., & Loomba, R. S. (2025) · Nature Reviews Disease Primers · doi:10.1038/s41572-025-00599-1 · Cited by 336 · see citing works
Self-citationWhat is the pipeline for future medications for obesity?
Melson, E., Ashraf, U., Papamargaritis, D., & Davies, M. J. (2025) · International Journal of Obesity · doi:10.1038/s41366-024-01473-y · Cited by 332 · cited 1× · see citing works
“Tirzepatide (Zepbound) has received recent FDA approval for chronic weight management alongside GLP-1 receptor agonist liraglutide (Saxenda) and semaglutide (Wegovy), following the demonstration of over 20% mean weight loss achieved in non-diabetic patients with obesity [105–110].”
Simon, T. G., Roelstraete, B., Hagström, H., Sundström, J., & Ludvigsson, J. F. (2021) · Gut · doi:10.1136/gutjnl-2021-325724 · Cited by 324 · see citing works
Kosiborod, M., Deanfield, J. E., Pratley, R. E., Borlaug, B. A., Butler, J., Davies, M. J., Emerson, S. S., Kahn, S. E., Kitzman, D. W., Lingvay, I., et al. (2024) · The Lancet · doi:10.1016/s0140-6736(24)01643-x · Cited by 323 · see citing works
Zhang, Q., Delessa, C. T., Augustin, R., Bakhti, M., Colldén, G., Drucker, D. J., Feuchtinger, A., Caceres, C. G., Grandl, G., Harger, A., et al. (2021) · Cell Metabolism · doi:10.1016/j.cmet.2021.01.015 · Cited by 322 · see citing works
Sanyal, A. J., Kaplan, L. M., Frias, J. P., Brouwers, B., Wu, Q., Thomas, M. K., Harris, C., Schloot, N. C., Du, Y., Mather, K. J., et al. (2024) · Nature Medicine · doi:10.1038/s41591-024-03018-2 · Cited by 315 · see citing works
Deanfield, J. E., Verma, S., Scirica, B. M., Kahn, S. E., Emerson, S. S., Ryan, D. H., Lingvay, I., Colhoun, H. M., Plutzky, J., Kosiborod, M., et al. (2024) · The Lancet · doi:10.1016/s0140-6736(24)01498-3 · Cited by 302 · see citing works
GLP-1 and weight loss: unraveling the diverse neural circuitry
Kanoski, S. E., Hayes, M. R., & Skibicka, K. P. (2016) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.00520.2015 · Cited by 290 · see citing works
Contribution of adipose tissue and de novo lipogenesis to nonalcoholic fatty liver disease
Tamura, S., & Shimomura, I. (2005) · Journal of Clinical Investigation · doi:10.1172/jci24930 · Cited by 288 · see citing works
Regulation of Glucose Homeostasis by GLP-1
Nadkarni, P., Chepurny, O. G., & Holz, G. G. (2014) · Progress in Molecular Biology and Translational Science · doi:10.1016/b978-0-12-800101-1.00002-8 · Cited by 287 · see citing works
Pancreatic signals controlling food intake; insulin, glucagon and amylin
Woods, S. C., Lutz, T. A., Geary, N., & Langhans, W. (2006) · Philosophical Transactions of the Royal Society B Biological Sciences · doi:10.1098/rstb.2006.1858 · Cited by 286 · see citing works
Nevola, R., Epifani, R., Imbriani, S., Tortorella, G., Aprea, C., Galiero, R., Rinaldi, L., Marfella, R., & Sasso, F. C. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24021703 · Cited by 286 · see citing works
Mechanisms of the free fatty acid-induced increase in hepatic glucose production
Lam, T. K. T., Carpentier, A. C., Lewis, G. F., van de Werve, G., Fantus, I. G., & Giacca, A. (2003) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00033.2003 · Cited by 285 · see citing works
Boland, M. L., Laker, R. C., Mather, K., Nawrocki, A., Oldham, S., Boland, B. B., Lewis, H., Conway, J., Naylor, J., Guionaud, S., et al. (2020) · Nature Metabolism · doi:10.1038/s42255-020-0209-6 · Cited by 270 · see citing works
Klausen, M. K., Jensen, M. E., Møller, M., Le Dous, N., Jensen, A.-M. Ø., Zeeman, V. A., Johannsen, C.-F., Lee, A., Thomsen, G. K., Macoveanu, J., et al. (2022) · JCI Insight · doi:10.1172/jci.insight.159863 · Cited by 262 · see citing works
Tan, T. M., Field, B. C. T., McCullough, K. A., Troke, R. C., Chambers, E. S., Salem, V., Gonzalez Maffe, J., Baynes, K. C. R., De Silva, A., Viardot, A., et al. (2013) · Diabetes · doi:10.2337/db12-0797 · Cited by 258 · see citing works
GIPR agonism mediates weight-independent insulin sensitization by tirzepatide in obese mice
Samms, R. J., Christe, M. E., Collins, K. A. L., Pirro, V., Droz, B. A., Holland, A. K., Friedrich, J. L., Wojnicki, S., Konkol, D. L., Cosgrove, R., et al. (2021) · Journal of Clinical Investigation · doi:10.1172/jci146353 · Cited by 256 · see citing works
Unimolecular Polypharmacy for Treatment of Diabetes and Obesity
Tschöp, M. H., Finan, B., Clemmensen, C., Gelfanov, V. M., Pérez–Tilve, D., Müller, T. D., & DiMarchi, R. D. (2016) · Cell Metabolism · doi:10.1016/j.cmet.2016.06.021 · Cited by 232 · see citing works
An adipocentric perspective on the development and progression of non-alcoholic fatty liver disease
Lee, E., Korf, H., & Vidal‐Puig, A. (2023) · Journal of Hepatology · doi:10.1016/j.jhep.2023.01.024 · Cited by 228 · see citing works
Glucagon Receptor Signaling and Lipid Metabolism
Galsgaard, K. D., Pedersen, J., Knop, F. K., Holst, J. J., & Wewer Albrechtsen, N. J. (2019) · Frontiers in Physiology · doi:10.3389/fphys.2019.00413 · Cited by 218 · see citing works
Incretins (GLP-1 receptor agonists and dual/triple agonists) and the liver
Newsome, P. N., & Ambery, P. (2023) · Journal of Hepatology · doi:10.1016/j.jhep.2023.07.033 · Cited by 211 · see citing works
Borner, T., Geisler, C. E., Fortin, S. M., Cosgrove, R., Alsina-Fernandez, J., Dogra, M., Doebley, S., Sanchez-Navarro, M. J., Leon, R. M., Gaisinsky, J., et al. (2021) · Diabetes · doi:10.2337/db21-0459 · Cited by 202 · see citing works
Hvidberg, A., Nielsen, M.-B., Hilsted, J., Ørskov, C., & Holst, J. J. (1994) · Metabolism · doi:10.1016/0026-0495(94)90164-3 · Cited by 195 · see citing works
Gasbjerg, L. S., Helsted, M. M., Hartmann, B., Jensen, M. H., Gabe, M. B. N., Sparre-Ulrich, A. H., Veedfald, S., Stensen, S., Lanng, A. R., Bergmann, N. C., et al. (2019) · Diabetes · doi:10.2337/db18-1123 · Cited by 193 · see citing works
An inter-organ neural circuit for appetite suppression
Zhang, T., Perkins, M. H., Chang, H., Han, W., & de Araujo, I. E. (2022) · Cell · doi:10.1016/j.cell.2022.05.007 · Cited by 192 · see citing works
The central GLP-1: implications for food and drug reward
Skibicka, K. P. (2013) · Frontiers in Neuroscience · doi:10.3389/fnins.2013.00181 · Cited by 188 · see citing works
PARACRINE INTERACTIONS WITHIN THE PANCREATIC ISLET DETERMINE THE GLYCEMIC SET POINT
Rodriguez-Diaz, R., Molano, R., Weitz, J., Abdulreda, M., Berman, D., Leibiger, B., Leibiger, I., Kenyon, N., Ricordi, C., Pileggi, A., et al. (2018) · Cell Metabolism · doi:10.1016/j.cmet.2018.01.015 · Cited by 188 · see citing works
Asmar, M., Simonsen, L., Madsbad, S., Stallknecht, B., Holst, J. J., & Bülow, J. (2010) · Diabetes · doi:10.2337/db10-0098 · Cited by 184 · see citing works
Homeostasis of Glucose and Lipid in Non-Alcoholic Fatty Liver Disease
Chao, H., Chao, S.-W., Lin, H., Ku, H., & Cheng, C. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20020298 · Cited by 183 · see citing works
Extracellular Matrix Remodeling in Chronic Liver Disease
Ortiz, C., Schierwagen, R., Schaefer, L., Klein, S., Trepat, X., & Trebicka, J. (2021) · Current Tissue Microenvironment Reports · doi:10.1007/s43152-021-00030-3 · Cited by 183 · see citing works
Glucagon-like Peptide-1 Receptor-based Therapeutics for Metabolic Liver Disease
Yabut, J. M., & Drucker, D. J. (2022) · Endocrine Reviews · doi:10.1210/endrev/bnac018 · Cited by 180 · see citing works
Harrison, S. A., Rolph, T., Knott, M., & Dubourg, J. (2024) · Journal of Hepatology · doi:10.1016/j.jhep.2024.04.034 · Cited by 176 · see citing works
Guzman, C. B., Zhang, X. M., Liu, R., Regev, A., Shankar, S., Garhyan, P., Pillai, S. G., Kazda, C., Chalasani, N., & Hardy, T. A. (2017) · Diabetes, Obesity and Metabolism · doi:10.1111/dom.12958 · Cited by 172 · see citing works
Insulin action in adipocytes, adipose remodeling, and systemic effects
Santoro, A. N., McGraw, T. E., & Kahn, B. B. (2021) · Cell Metabolism · doi:10.1016/j.cmet.2021.03.019 · Cited by 170 · see citing works
The benefits of GLP-1 drugs beyond obesity
Drucker, D. J. (2024) · Science · doi:10.1126/science.adn4128 · Cited by 169 · see citing works
Kanwal, F., Kramer, J. R., Li, L., Yang, Y., Cao, Y., Yu, X., Samuel, R. E., Ali, B., Desiderio, R., Cholankeril, G. T., et al. (2024) · JAMA Internal Medicine · doi:10.1001/jamainternmed.2024.4661 · Cited by 163 · see citing works
Elevated hepatic DPP4 activity promotes insulin resistance and non-alcoholic fatty liver disease
Baumeier, C., Schlüter, L., Saussenthaler, S., Laeger, T., Rödiger, M., Alaze, S. A., Fritsche, L., Häring, H., Stefan, N., Fritsche, A., et al. (2017) · Molecular Metabolism · doi:10.1016/j.molmet.2017.07.016 · Cited by 162 · see citing works
Targeting the Incretin/Glucagon System With Triagonists to Treat Diabetes
Capozzi, M. E., DiMarchi, R. D., Tschöp, M. H., Finan, B., & Campbell, J. E. (2018) · Endocrine Reviews · doi:10.1210/er.2018-00117 · Cited by 153 · see citing works
Semaglutide and Tirzepatide reduce alcohol consumption in individuals with obesity
Quddos, F., Hubshman, Z., Tegge, A. N., Sane, D., Marti, E., Kablinger, A. S., Gatchalian, K. M., Kelly, A. L., DiFeliceantonio, A. G., & Bickel, W. K. (2023) · Scientific Reports · doi:10.1038/s41598-023-48267-2 · Cited by 151 · see citing works
Zimmermann, T., Thomas, L., Baader-Pagler, T., Haebel, P., Simon, E., Reindl, W., Bajrami, B., Rist, W., Uphues, I., Drucker, D. J., et al. (2022) · Molecular Metabolism · doi:10.1016/j.molmet.2022.101633 · Cited by 149 · see citing works
Campbell, J. E., Müller, T. D., Finan, B., DiMarchi, R. D., Tschöp, M. H., & D’Alessio, D. A. (2023) · Cell Metabolism · doi:10.1016/j.cmet.2023.07.010 · Cited by 149 · see citing works
Wang, W. J., Volkow, N. D., Berger, N. A., Davis, P. B., Kaelber, D. C., & Xu, R. (2024) · Nature Communications · doi:10.1038/s41467-024-48780-6 · Cited by 138 · see citing works
Selective hepatic vagotomy blocks pancreatic glucagon's satiety effect
GEARY, N., & SMITH, G. (1983) · Physiology & Behavior · doi:10.1016/0031-9384(83)90207-x · Cited by 134 · see citing works
Day, J. W., Gelfanov, V., Smiley, D., Carrington, P. E., Eiermann, G., Chicchi, G., Erion, M. D., Gidda, J., Thornberry, N. A., Tschöp, M. H., et al. (2012) · Peptide Science · doi:10.1002/bip.22072 · Cited by 133 · see citing works
Targeting the GIPR for obesity: To agonize or antagonize? Potential mechanisms
Campbell, J. E. (2021) · Molecular Metabolism · doi:10.1016/j.molmet.2020.101139 · Cited by 133 · see citing works
Glucagon acts in the liver to control spontaneous meal size in rats
Geary, N., Le Sauter, J., & Noh, U. (1993) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.1993.264.1.r116 · Cited by 128 · see citing works
Wang, Y., Parlevliet, E. T., Geerling, J. J., van der Tuin, S. J. L., Zhang, H., Bieghs, V, Jawad, A. H. M., Shiri‐Sverdlov, R., Bot, I., de Jager, S. C. A., et al. (2014) · British Journal of Pharmacology · doi:10.1111/bph.12490 · Cited by 126 · see citing works
Targher, G., Mantovani, A., & Byrne, C. D. (2023) · The Lancet Gastroenterology & Hepatology · doi:10.1016/s2468-1253(22)00338-7 · Cited by 121 · see citing works
Torre, S. D. (2020) · Frontiers in Endocrinology · doi:10.3389/fendo.2020.572490 · Cited by 118 · see citing works
100 years of glucagon and 100 more
Wewer Albrechtsen, N. J., Holst, J. J., Cherrington, A. D., Finan, B., Gluud, L. L., Dean, E. D., Campbell, J. E., Bloom, S. R., Tan, T. M.-M., Knop, F. K., et al. (2023) · Diabetologia · doi:10.1007/s00125-023-05947-y · Cited by 117 · see citing works
Bernsmeier, C., Meyer‐Gerspach, A. C., Blaser, L. S., Jeker, L., Steinert, R. E., Heim, M. H., & Beglinger, C. (2014) · PLoS ONE · doi:10.1371/journal.pone.0087488 · Cited by 110 · see citing works
GLP-1 Influences Food and Drug Reward
Hayes, M. R., & Schmidt, H. D. (2016) · Current Opinion in Behavioral Sciences · doi:10.1016/j.cobeha.2016.02.005 · Cited by 108 · see citing works
Jall, S., Sachs, S., Clemmensen, C., Finan, B., Neff, F., DiMarchi, R. D., Tschöp, M. H., Müller, T. D., & Hofmann, S. M. (2017) · Molecular Metabolism · doi:10.1016/j.molmet.2017.02.002 · Cited by 107 · see citing works
Paracrine control of α-cell glucagon exocytosis is compromised in human type-2 diabetes
Omar-Hmeadi, M., Lund, P.-E., Gandasi, N. R., Tengholm, A., & Barg, S. (2020) · Nature Communications · doi:10.1038/s41467-020-15717-8 · Cited by 105 · see citing works
Alpha cell regulation of beta cell function
Moede, T., Leibiger, I., & Berggren, P. (2020) · Diabetologia · doi:10.1007/s00125-020-05196-3 · Cited by 103 · see citing works
Malhotra, A., Bednařík, J., Chakladar, S., Dunn, J. P., Weaver, T. E., Grunstein, R. R., Fietze, I., Redline, S. S., Azarbarzin, A., Sands, S. A., et al. (2024) · Contemporary Clinical Trials · doi:10.1016/j.cct.2024.107516 · Cited by 103 · see citing works
The role of GIP in α-cells and glucagon secretion
EL, K. M., & Campbell, J. E. (2019) · Peptides · doi:10.1016/j.peptides.2019.170213 · Cited by 97 · see citing works
Beaudry, J. L., Kaur, K. D., Varin, E. M., Baggio, L. L., Cao, X., Mulvihill, E. E., Stern, J. H., Campbell, J. E., Scherer, P. E., & Drucker, D. J. (2019) · Molecular Metabolism · doi:10.1016/j.molmet.2019.01.011 · Cited by 88 · see citing works
The molecular pharmacology of glucagon agonists in diabetes and obesity
Novikoff, A., & Müller, T. D. (2023) · Peptides · doi:10.1016/j.peptides.2023.171003 · Cited by 82 · see citing works
Jerlhag, E. (2023) · Frontiers in Pharmacology · doi:10.3389/fphar.2023.1063033 · Cited by 80 · see citing works
Thondam, S. K., Cuthbertson, D. J., & Wilding, J. P. H. (2020) · Peptides · doi:10.1016/j.peptides.2019.170208 · Cited by 77 · see citing works
Elsaid, M. I., Li, N., Firkins, S. A., Rustgi, V. K., Paskett, E. D., Acharya, C., Reddy, K. R., Chiang, C. W., & Mumtaz, K. (2024) · Alimentary Pharmacology & Therapeutics · doi:10.1111/apt.17925 · Cited by 77 · see citing works
Ijuin, T., & Takenawa, T. (2012) · Journal of Biological Chemistry · doi:10.1074/jbc.m111.335539 · Cited by 73 · see citing works
Rizvi, A. A., & Rizzo, M. (2022) · Diabetes Metabolic Syndrome and Obesity · doi:10.2147/dmso.s351982 · Cited by 68 · see citing works
GLP-1 based therapies: clinical implications for gastroenterologists
Smits, M. M., van Raalte, D. H., Tonneijck, L., Muskiet, M. H. A., Kramer, M. H. H., & Cahen, D. L. (2016) · Gut · doi:10.1136/gutjnl-2015-310572 · Cited by 61 · see citing works
Hepatic portal infusion of glucagon antibodies increases spontaneous meal size in rats
Sauter, J. L., Noh, U., & Geary, N. (1991) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.1991.261.1.r162 · Cited by 57 · see citing works
Lipid Transport in Brown Adipocyte Thermogenesis
Wade, G., McGahee, A., Ntambi, J. M., & Simcox, J. (2021) · Frontiers in Physiology · doi:10.3389/fphys.2021.787535 · Cited by 53 · see citing works
FLOW trial stopped early due to evidence of renal protection with semaglutide
Gragnano, F., De Sio, V., & Calabrò, P. (2024) · European Heart Journal - Cardiovascular Pharmacotherapy · doi:10.1093/ehjcvp/pvad080 · Cited by 51 · see citing works
Glucagon, GLP-1 and Thermogenesis
González-García, I., Milbank, E., Diéguez, C., López, M., & Contreras, C. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20143445 · Cited by 49 · see citing works
Samms, R. J., Sloop, K. W., Gribble, F. M., Reimann, F., & Adriaenssens, A. E. (2021) · Diabetes · doi:10.2337/dbi21-0002 · Cited by 49 · see citing works
Physiology of Energy Expenditure in the Weight‐Reduced State
Ravussin, É., Smith, S. R., & Ferrante, A. W. (2021) · Obesity · doi:10.1002/oby.23095 · Cited by 48 · see citing works
Is Glucagon Receptor Activation the Thermogenic Solution for Treating Obesity?
Conceição-Furber, E., Coskun, T., Sloop, K. W., & Samms, R. J. (2022) · Frontiers in Endocrinology · doi:10.3389/fendo.2022.868037 · Cited by 48 · see citing works
Dragonieri, S., Portacci, A., Quaranta, V. N., Carratù, P., Lázár, Z., Carpagnano, G. E., & Bikov, A. (2024) · Diseases · doi:10.3390/diseases12090224 · Cited by 48 · see citing works
Jakubowska, A., Roux, C. W. L., & Viljoen, A. (2024) · Endocrinology and Metabolism · doi:10.3803/enm.2024.1942 · Cited by 45 · see citing works
Lesion of vagal afferent terminals impairs glucagon-induced suppression of food intake
Weatherford, S. C., & Ritter, S. (1988) · Physiology & Behavior · doi:10.1016/0031-9384(88)90220-x · Cited by 43 · see citing works
Le, K. D. R., Le, K., & Foo, F. (2024) · Pharmacy · doi:10.3390/pharmacy12010011 · Cited by 43 · see citing works
Péterfi, Z., Szilvásy‐Szabó, A., Farkas, E., Ruska, Y., Pyke, C., Knudsen, L. B., & Fekete, C. (2020) · Neuroendocrinology · doi:10.1159/000512806 · Cited by 42 · see citing works
Metabolic responses and benefits of glucagon‐like peptide‐1 (GLP‐1) receptor ligands
Tanday, N., Flatt, P. R., & Irwin, N. (2021) · British Journal of Pharmacology · doi:10.1111/bph.15485 · Cited by 42 · see citing works
Endogenous GLP-1 as a key self-defense molecule against lipotoxicity in pancreatic islets
HUANG, C., YUAN, L., & CAO, S. (2015) · International Journal of Molecular Medicine · doi:10.3892/ijmm.2015.2207 · Cited by 41 · see citing works
Kuo, C., Chuang, M., Li, C., Tsai, Y., Huang, P., Kuo, H., & Lai, C. (2025) · Alimentary Pharmacology & Therapeutics · doi:10.1111/apt.18502 · Cited by 38 · see citing works
Nakatani, M., Kokubo, M., Ohsawa, Y., Sunada, Y., & Tsuchida, K. (2011) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00430.2010 · Cited by 34 · see citing works
Long-term major adverse liver outcomes in 1,260 patients with non-cirrhotic NAFLD
Akbari, C., Dodd, M., Stal, P. I., Nasr, P., Ekstedt, M., Kechagias, S., Vessby, J., Rorsman, F., Zhang, X., Wang, T., et al. (2023) · JHEP Reports · doi:10.1016/j.jhepr.2023.100915 · Cited by 29 · see citing works
Brennan, P., Tavabie, O. D., Li, W., Marjot, T., Corless, L., Fallowfield, J. A., Jarvis, H., Mansour, D., McPherson, S., Rosenberg, W. M., et al. (2024) · The Lancet. Gastroenterology & hepatology · doi:10.1016/s2468-1253(23)00453-3 · Cited by 25 · see citing works
GIP: An Inconsequential Incretin or Not?
Pratley, R. E. (2010) · Diabetes Care · doi:10.2337/dc10-0704 · Cited by 19 · see citing works
Xie, C., Alkhouri, N., & Elfeki, M. A. (2024) · World Journal of Hepatology · doi:10.4254/wjh.v16.i5.731 · Cited by 18 · see citing works
Wang, Y., Lin, Z., Wan, H., Zhang, W., Xia, F., Chen, Y., Chen, X., Wang, C., Chen, C., Wang, N., et al. (2021) · European Journal of Gastroenterology & Hepatology · doi:10.1097/meg.0000000000002269 · Cited by 11 · see citing works
Ciccarelli, G., Giuseppe, G. D., Cinti, F., Moffa, S., Mezza, T., & Giaccari, A. (2023) · Diabetes/Metabolism Research and Reviews · doi:10.1002/dmrr.3668 · Cited by 11 · see citing works
FDA Approves Semaglutide to Reduce Risk of Kidney Disease Progression
Anderer, S. (2025) · JAMA · doi:10.1001/jama.2025.0548 · Cited by 10 · see citing works
Alkhouri, N., Tomah, S., Suschak, J. J., et al. (2024) · Journal of Hepatology · doi:10.1016/s0168-8278(24)01555-1 · Cited by 1 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Ganamurali, N., & Sabarathinam, S. (2026) · Clinical Pharmacology in Drug Development · doi:10.1002/cpdd.70001 · Cited by 8 · see citing works
- Authors
- Zafer, M., Tavaglione, F., Romero‐Gómez, M., & Loomba, R.
- Affiliations
- University of California San Diego (US)
- Instituto de Biomedicina de Sevilla (ES)
- Corresponding author
- Loomba, Rohit
- Venue
- Alimentary Pharmacology & Therapeutics
- Publisher
- Wiley
- Published
- 2025-05-13
- Volume
- 61
- Issue
- 12
- Pages
- 1872-1888
- ISSN
- 0269-2813 (ISSN-L)
- 1365-2036
- PMC
- PMC12323726
- OpenAlex
- W4410379565
- Semantic Scholar
- 6a3a31395451bab73fd325157a78718a180634d5
- Cited by
- 47
- References
- 135
- Citations by year
- 2026: 36 · 2025: 11
- FWCI
- 7.22
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Alimentary Pharmacology & Therapeutics (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- DIGITAL.CSIC (Spanish National Research Council (CSIC)) (acceptedVersion)
- Funders
- National Center for Advancing Translational Sciences (5UL1TR001442)
- National Institute of Diabetes and Digestive and Kidney Diseases (U01DK061734 U01DK130190 R01DK106419 R01DK121378)
- National Heart, Lung, and Blood Institute (P01HL147835)
- National Institute on Alcohol Abuse and Alcoholism (U01AA029019)
- Topics
- Health Sciences › Medicine › Epidemiology › Liver Disease Diagnosis and Treatment
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
- Health Sciences › Medicine › Pharmacology › Pharmacology and Obesity Treatment
- Keywords
- GLP-1 receptor agonists, glucagon receptor agonist, glucose-dependent insulinotropic polypeptide, nonalcoholic steatohepatitis, non-alcoholic fatty liver disease, tirzepatide, survodutide, semaglutide, liver fibrosis, disease-modifying therapy, weight loss, cardiometabolic benefits, gastrointestinal adverse effects
- MeSH terms
- Glucagon-Like Peptide-1 Receptor, Glucagon-Like Peptide-1 Receptor Agonists, Gastric Inhibitory Polypeptide, Humans, Receptors, Gastrointestinal Hormone, Receptors, Glucagon, Non-alcoholic Fatty Liver Disease
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
