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Adie Viljoen 2 Articles
Diabetes, obesity and metabolism
The Road towards Triple Agonists: Glucagon-Like Peptide 1, Glucose-Dependent Insulinotropic Polypeptide and Glucagon Receptor - An Update
Agnieszka Jakubowska, Carel W. le Roux, Adie Viljoen
Endocrinol Metab. 2024;39(1):12-22.   Published online February 14, 2024
DOI: https://doi.org/10.3803/EnM.2024.1942
  • 22,657 View
  • 786 Download
  • 15 Web of Science
  • 20 Crossref
AbstractAbstract PDFPubReader   ePub   
Obesity is the fifth leading risk factor for global deaths with numbers continuing to increase worldwide. In the last 20 years, the emergence of pharmacological treatments for obesity based on gastrointestinal hormones has transformed the therapeutic landscape. The successful development of glucagon-like peptide-1 (GLP-1) receptor agonists, followed by the synergistic combined effect of glucose-dependent insulinotropic polypeptide (GIP)/GLP-1 receptor agonists achieved remarkable weight loss and glycemic control in those with the diseases of obesity and type 2 diabetes. The multiple cardiometabolic benefits include improving glycemic control, lipid profiles, blood pressure, inflammation, and hepatic steatosis. The 2023 phase 2 double-blind, randomized controlled trial evaluating a GLP-1/GIP/glucagon receptor triagonist (retatrutide) in patients with the disease of obesity reported 24.2% weight loss at 48 weeks with 12 mg retatrutide. This review evaluates the current available evidence for GLP-1 receptor agonists, dual GLP-1/GIP receptor co-agonists with a focus on GLP-1/GIP/glucagon receptor triagonists and discusses the potential future benefits and research directions.

Citations

Citations to this article as recorded by  
  • Gastrointestinal safety of semaglutide and tirzepatide vs. placebo in obese individuals without diabetes: a systematic review and meta analysis
    Moaz Safwan, Mariam Safwan Bourgleh, Shahad Abdullah Alotaibi, Eman Alotaibi, Abdulsalam Al-Ruqi, Fathiya El Raeya
    Annals of Saudi Medicine.2025; 45(2): 129.     CrossRef
  • Glucose-dependent insulinotropic peptide and beyond: co-agonist innovations in the treatment of metabolic diseases
    Chenxu Zhou, Binbin Gong, Xiyu Liu, Guoqiang Hu, Lidan Sun
    European Journal of Pharmacology.2025; 999: 177681.     CrossRef
  • Advancing Cardiovascular, Kidney, and Metabolic Medicine: A Narrative Review of Insights and Innovations for the Future
    Kevin Fernando, Derek Connolly, Eimear Darcy, Marc Evans, William Hinchliffe, Patrick Holmes, W. David Strain
    Diabetes Therapy.2025; 16(6): 1155.     CrossRef
  • 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
    Maryam Zafer, Federica Tavaglione, Manuel Romero‐Gómez, Rohit Loomba
    Alimentary Pharmacology & Therapeutics.2025; 61(12): 1872.     CrossRef
  • Retatrutide—A Game Changer in Obesity Pharmacotherapy
    Vasiliki Katsi, Georgios Koutsopoulos, Christos Fragoulis, Kyriakos Dimitriadis, Konstantinos Tsioufis
    Biomolecules.2025; 15(6): 796.     CrossRef
  • The role of broad bean albumin 1b on GIP and GLP-1 mediated alterations to glucose metabolism in diabetic mice
    Feifei Han, Lu Jin, Lulu Zhou, Qi Liu, MengLu Ding, Weilin Liu, Jianzhong Han
    npj Science of Food.2025;[Epub]     CrossRef
  • Next Generation Dual GLP-1/GIP, GLP-1/Glucagon, and Triple GLP-1/GIP/Glucagon Agonists: A Literature Review
    Jimmy Wen, Denise Nadora, Alina Truong, Ethan Bernstein, Christiane How-Volkman, Adam Razick, Daniel Razick, Muhammad Karabala, Eldo Frezza
    Nutrition, Metabolism and Cardiovascular Diseases.2025; : 104213.     CrossRef
  • Retatrutide: A novel approach in the treatment of obesity, diabetes mellitus, and MASLD (metabolic dysfunction-associated steatotic liver disease)
    Robert Prosecký, Klaudia Hálová Karoliová
    Klinická farmakologie a farmacie.2025; 39(2): 122.     CrossRef
  • New Mechanisms to Prevent Heart Failure with Preserved Ejection Fraction Using Glucagon-like Peptide-1 Receptor Agonism (GLP-1 RA) in Metabolic Syndrome and in Type 2 Diabetes: A Review
    Jorge E. Jalil, Luigi Gabrielli, María Paz Ocaranza, Paul MacNab, Rodrigo Fernández, Bruno Grassi, Paulina Jofré, Hugo Verdejo, Monica Acevedo, Samuel Cordova, Luis Sanhueza, Douglas Greig
    International Journal of Molecular Sciences.2024; 25(8): 4407.     CrossRef
  • New Molecules in Type 2 Diabetes: Advancements, Challenges and Future Directions
    Kyriazoula Chatzianagnostou, Melania Gaggini, Adrian Suman Florentin, Ludovica Simonini, Cristina Vassalle
    International Journal of Molecular Sciences.2024; 25(11): 6218.     CrossRef
  • Glucagon-like peptide-1 receptor agonists and sodium-glucose cotransporter 2 inhibitors, anti-diabetic drugs in heart failure and cognitive impairment: potential mechanisms of the protective effects
    Maria Antonietta Riemma, Elena Mele, Maria Donniacuo, Marialucia Telesca, Gabriella Bellocchio, Giuseppe Castaldo, Francesco Rossi, Antonella De Angelis, Donato Cappetta, Konrad Urbanek, Liberato Berrino
    Frontiers in Pharmacology.2024;[Epub]     CrossRef
  • Mechanisms of Glucagon Receptor Agonism and GLP-1/Glucagon/GIP Receptor Triple Agonism for Treatment of Diabetes and Obesity
    Se Hee Min
    The Journal of Korean Diabetes.2024; 25(2): 82.     CrossRef
  • Structural insights into the triple agonism at GLP-1R, GIPR and GCGR manifested by retatrutide
    Wenzhuo Li, Qingtong Zhou, Zhaotong Cong, Qingning Yuan, Wenxin Li, Fenghui Zhao, H. Eric Xu, Li-Hua Zhao, Dehua Yang, Ming-Wei Wang
    Cell Discovery.2024;[Epub]     CrossRef
  • Molecular Mechanisms behind Obesity and Their Potential Exploitation in Current and Future Therapy
    Michał Nicze, Adrianna Dec, Maciej Borówka, Damian Krzyżak, Aleksandra Bołdys, Łukasz Bułdak, Bogusław Okopień
    International Journal of Molecular Sciences.2024; 25(15): 8202.     CrossRef
  • Semaglutide “Ozempic” Face and Implications in Cosmetic Dermatology
    Karen Montecinos, Barbara Kania, David J. Goldberg
    Dermatological Reviews.2024;[Epub]     CrossRef
  • GLP-1 Receptor Agonists and SGLT2 Inhibitors in Type 2 Diabetes: Pleiotropic Cardiometabolic Effects and Add-on Value of a Combined Therapy
    André J. Scheen
    Drugs.2024; 84(11): 1347.     CrossRef
  • Retatrutide
    Nathan Ramsbacher
    Clinical Diabetes.2024; 42(4): 579.     CrossRef
  • The power of three: Retatrutide's role in modern obesity and diabetes therapy
    Toufik Abdul-Rahman, Poulami Roy, Fatma Kamal Ahmed, Jann Ludwig Mueller-Gomez, Sarmistha Sarkar, Neil Garg, Victor Oluwafemi Femi-Lawal, Andrew Awuah Wireko, Hala Ibrahim Thaalibi, Muhammad Usman Hashmi, Andrew Sefenu Dzebu, Sewar Basheer Banimusa, Aayus
    European Journal of Pharmacology.2024; 985: 177095.     CrossRef
  • Old and new anti-obesity drugs
    Salimeh Dodangeh, Shirin Hasani-Ranjbar
    Journal of Diabetes & Metabolic Disorders.2024;[Epub]     CrossRef
  • Innovative approaches to the treatment of obesity: from pharmacotherapy to nanomedicine
    T. I. Romantsova
    Obesity and metabolism.2024; 21(4): 389.     CrossRef
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Diabetes, Obesity and Metabolism
Glucagon-Like Peptide 1 Therapy: From Discovery to Type 2 Diabetes and Beyond
Adie Viljoen, Stephen C. Bain
Endocrinol Metab. 2023;38(1):25-33.   Published online February 6, 2023
DOI: https://doi.org/10.3803/EnM.2022.1642
  • 7,939 View
  • 409 Download
  • 7 Web of Science
  • 6 Crossref
AbstractAbstract PDFPubReader   ePub   
The therapeutic benefits of the incretin hormone, glucagon-like peptide 1 (GLP1), for people with type 2 diabetes and/or obesity, are now firmly established. The evidence-base arising from head-to-head comparative effectiveness studies in people with type 2 diabetes, as well as the recommendations by professional guidelines suggest that GLP1 receptor agonists should replace more traditional treatment options such as sulfonylureas and dipeptidyl-peptidase 4 (DPP4) inhibitors. Furthermore, their benefits in reducing cardiovascular events in people with type 2 diabetes beyond improvements in glycaemic control has led to numerous clinical trials seeking to translate this benefit beyond type 2 diabetes. Following early trial results their therapeutic benefit is currently being tested in other conditions including fatty liver disease, kidney disease, and Alzheimer’s disease.

Citations

Citations to this article as recorded by  
  • The Road towards Triple Agonists: Glucagon-Like Peptide 1, Glucose-Dependent Insulinotropic Polypeptide and Glucagon Receptor - An Update
    Agnieszka Jakubowska, Carel W. le Roux, Adie Viljoen
    Endocrinology and Metabolism.2024; 39(1): 12.     CrossRef
  • The Association of Circulating Glucagon-Like Peptide-1 with Cognitive Functions and Biomarkers in Alzheimer’s Disease
    Mengqing Liu, Nenghong Ma, Xiao Yang, Miao Sun, Xiaowen Li, Yuhui Liu, Qing Chang, Changchun Hei, Jian-Hong Wang
    Journal of Alzheimer's Disease.2024; 99(2): 525.     CrossRef
  • Energy balance and obesity: the emerging role of glucagon like peptide-1 receptor agonists
    Noémie Beauregard, Kurt McInnis, Gary S. Goldfield, Éric Doucet
    Current Opinion in Clinical Nutrition & Metabolic Care.2024; 27(6): 472.     CrossRef
  • Glucagon-like peptide 1 receptor agonists: cardiovascular benefits and mechanisms of action
    John R. Ussher, Daniel J. Drucker
    Nature Reviews Cardiology.2023; 20(7): 463.     CrossRef
  • A new class of glucose-lowering therapy for type 2 diabetes: the latest development in the incretin arena
    Stephen C Bain, Thinzar Min
    The Lancet.2023; 402(10401): 504.     CrossRef
  • Flattening the biological age curve by improving metabolic health: to taurine or not to taurine, that’ s the question
    Kwok M. Ho, Anna Lee, William Wu, Matthew T.V. Chan, Lowell Ling, Jeffrey Lipman, Jason Roberts, Edward Litton, Gavin M. Joynt, Martin Wong
    Journal of Geriatric Cardiology.2023; 20(11): 813.     CrossRef
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