IDF Diabetes Atlas, 10th Edition [Internet]. Brussels, Belgium: Internation Diabetes Federation; 2021 [cited 2023 Sep 22]. Available from: https://www.diabetesatlas.org
Global health estimates 2020: deaths by cause, age, sex, by country and by region, 2000–2019. Geneva; 2020. https://www.who.int/data/global-health-estimates. Accessed 29 Nov 2023.
Chen W, Binbin G, Lidan S, Qiang Z, Jing H. Evolution of peptide YY analogs for the management of type 2 diabetes and obesity. Bioorg Chem. 2023;140: 106808.
Article CAS PubMed Google Scholar
Zhu W, Tanday N, Flatt PR, Irwin N. Pancreatic polypeptide revisited: potential therapeutic effects in obesity-diabetes. Peptides (NY). 2023;160: 170923.
Mathiesen DS, Lund A, Holst JJ, Knop FK, Lutz TA, Bagger JI. Therapy of endocrine disease: amylin and calcitonin – physiology and pharmacology. Eur J Endocrinol. 2022;186:R93-111.
Article CAS PubMed Google Scholar
Rehfeld JF. Premises for cholecystokinin and gastrin peptides in diabetes therapy. Clin Med Insights Endocrinol Diab. 2019;12:117955141988360.
Hammoud R, Drucker DJ. Beyond the pancreas: contrasting cardiometabolic actions of GIP and GLP1. Nat Rev Endocrinol. 2023;19:201–16.
Article CAS PubMed Google Scholar
Nauck MA, Quast DR, Wefers J, Pfeiffer AFH. The evolving story of incretins (GIP and GLP-1) in metabolic and cardiovascular disease: a pathophysiological update. Diabetes Obes Metab. 2021;23 Suppl 3:5–29. A detailed review of the functions of GLP-1, GIP, glucagon, and their role in pathogenesis of obesity and type 2 diabetes.
Alexander JT, Staab EM, Wan W, Franco M, Knitter A, Skandari MR, et al. The longer-term benefits and harms of glucagon-like peptide-1 receptor agonists: a systematic review and meta-analysis. J Gen Intern Med. 2022;37:415–38.
Whyte MB, Heald A, Field BC. Harnessing the incretin system with multi-agonists. EMJ Innovations. 2022. https://doi.org/10.33590/emjinnov/10115628
Pratt E, Ma X, Liu R, Robins D, Coskun T, Sloop KW, et al. Orforglipron ( <scp>LY3502970</scp> ), A novel, oral non-peptide glucagon-like peptide-1 receptor agonist: a phase 1b, multicentre, blinded, placebo-controlled, randomized, multiple-ascending-dose study in people with type 2 diabetes. Diabetes Obes Metab. 2023;25:2642–9.
Article CAS PubMed Google Scholar
Divino V, Boye KS, Lebrec J, DeKoven M, Norrbacka K. GLP-1 RA Treatment and dosing patterns among type 2 diabetes patients in six countries: a retrospective analysis of pharmacy claims data. Diab Ther. 2019;10:1067–88.
Hasib A. Multiagonist unimolecular peptides for obesity and type 2 diabetes: current advances and future directions. Clin Med Insights Endocrinol Diab. 2020;13:117955142090584.
Bhat VK, Kerr BD, Vasu S, Flatt PR, Gault VA. A DPP-IV-resistant triple-acting agonist of GIP, GLP-1 and glucagon receptors with potent glucose-lowering and insulinotropic actions in high-fat-fed mice. Diabetologia. 2013;56:1417–24.
Article CAS PubMed Google Scholar
Thondam SK, Cuthbertson DJ, Wilding JPH. The influence of glucose-dependent insulinotropic polypeptide (GIP) on human adipose tissue and fat metabolism: implications for obesity, type 2 diabetes and non-alcoholic fatty liver disease (NAFLD). Peptides (NY). 2019;125: 170208.
Mentis N, Vardarli I, Köthe LD, Holst JJ, Deacon CF, Theodorakis M, et al. GIP does not potentiate the antidiabetic effects of GLP-1 in hyperglycemic patients with type 2 diabetes. Diab. 2011;60:1270–6.
Bergmann NC, Lund A, Gasbjerg LS, Meessen ECE, Andersen MM, Bergmann S, et al. Effects of combined GIP and GLP-1 infusion on energy intake, appetite and energy expenditure in overweight/obese individuals: a randomised, crossover study. Diabetologia. 2019;62:665–75.
Article CAS PubMed Google Scholar
Meier JJ, Gallwitz B, Kask B, Deacon CF, Holst JJ, Schmidt WE, et al. Stimulation of insulin secretion by intravenous bolus injection and continuous infusion of gastric inhibitory polypeptide in patients with type 2 diabetes and healthy control subjects. Diabetes. 2004;53:S220–4.
Article CAS PubMed Google Scholar
Piteau S, Olver A, Kim S-J, Winter K, Pospisilik JA, Lynn F, et al. Reversal of islet GIP receptor down-regulation and resistance to GIP by reducing hyperglycemia in the Zucker rat. Biochem Biophys Res Commun. 2007;362:1007–12.
Article CAS PubMed Google Scholar
Novikoff A, O’Brien SL, Bernecker M, Grandl G, Kleinert M, Knerr PJ, et al. Spatiotemporal GLP-1 and GIP receptor signaling and trafficking/recycling dynamics induced by selected receptor mono- and dual-agonists. Mol Metab. 2021;49: 101181.
Article CAS PubMed PubMed Central Google Scholar
Holst JJ, Rosenkilde MM. GIP as a therapeutic target in diabetes and obesity: insight from incretin co-agonists. J Clin Endocrinol Metab. 2020;105:e2710–6.
Article PubMed PubMed Central Google Scholar
Frias JP, Bastyr EJ 3rd, Louis Vignati, Tschöp MH, Schmitt C, Owen K, Christensen RH, et al. The sustained effects of a dual GIP/GLP-1 receptor agonist, NNC0090–2746, in patients with type 2 diabetes. Cell Metab. 2017;26:343-352.e2.
Article CAS PubMed Google Scholar
Rosenstock J, Wysham C, Frias JP, Kaneko S, Lee CJ, Fernández Landó L, et al. Efficacy and safety of a novel dual GIP and GLP-1 receptor agonist tirzepatide in patients with type 2 diabetes (SURPASS-1): a double-blind, randomised, phase 3 trial. Lancet. 2021;398:143–55.
Article CAS PubMed Google Scholar
Samms RJ, Cosgrove R, Snider BM, Furber EC, Droz BA, Briere DA, et al. GIPR agonism inhibits PYY-induced nausea-like behavior. Diabet. 2022;71:1410–23.
Frias JP, Nauck MA, Van J, Kutner ME, Cui X, Benson C, et al. Efficacy and safety of LY3298176, a novel dual GIP and GLP-1 receptor agonist, in patients with type 2 diabetes: a randomised, placebo-controlled and active comparator-controlled phase 2 trial. Lancet. 2018;392:2180–93.
Article CAS PubMed Google Scholar
Brubaker PL, Drucker DJ. Structure-function of the glucagon receptor family of G protein-coupled receptors: the glucagon, GIP, GLP-1, and GLP-2 receptors. Recept Channels. 2002;8:179–88.
Article CAS PubMed Google Scholar
Day JW, Ottaway N, Patterson JT, Gelfanov V, Smiley D, Gidda J, et al. A new glucagon and GLP-1 co-agonist eliminates obesity in rodents. Nat Chem Biol. 2009;5:749–57.
Article CAS PubMed Google Scholar
Finan B, Ma T, Ottaway N, Müller TD, Habegger KM, Heppner KM, et al. Unimolecular dual incretins maximize metabolic benefits in rodents, monkeys, and humans. Sci Transl Med. 2013;5:209ra151.
Choi I, Lee J, Kim J, Park Y, Jung S, Kim Y, et al. Potent body weight loss and efficacy in a NASH animal model by a novel long-acting GLP-1/glucagon/GIP triple-agonist (HM15211). American Diabetes Association, 77th Scientific Sessions. San Diego, USA; 2017.
Bhat VK, Kerr BD, Flatt PR, Gault VA. A novel GIP-oxyntomodulin hybrid peptide acting through GIP, glucagon and GLP-1 receptors exhibits weight reducing and anti-diabetic properties. Biochem Pharmacol. 2013;85:1655–62.
Article CAS PubMed Google Scholar
Gault VA, Bhat VK, Irwin N, Flatt PR. A novel glucagon-like peptide-1 (GLP-1)/glucagon hybrid peptide with triple-acting agonist activity at glucose-dependent insulinotropic polypeptide, GLP-1, and glucagon receptors and therapeutic potential in high fat-fed mice. J Biol Chem. 2013;288:35581–91.
Article CAS PubMed PubMed Central Google Scholar
Finan B, Yang B, Ottaway N, Smiley DL, Ma T, Clemmensen C, et al. A rationally designed monomeric peptide triagonist corrects obesity and diabetes in rodents. Nat Med. 2014;21:27–36.
Trevaskis JL, Mack CM, Sun C, Soares CJ, D’Souza LJ, Levy Odile E, Lewis DY, et al. Improved glucose control and reduced body weight in rodents with dual mechanism of action peptide hybrids. PLoS ONE. 2013;8: e78154.
Article CAS PubMed PubMed Central Google Scholar
Xie Z, Hu J, Gu H, Li M, Chen J. Comparison of the efficacy and safety of 10 glucagon-like peptide-1 receptor agonists as add-on to metformin in patients with type 2 diabetes: a systematic review. Front Endocrinol (Lausanne). 2023;14:1244432. https://doi.org/10.3389/fendo.2023.1244432
Nauck MA, Mirna AEA, Quast DR. Meta-analysis of head-to-head clinical trials comparing incretin-based glucose-lowering medications and basal insulin: an update including recently developed glucagon-like peptide-1 (GLP-1) receptor agonists and the glucose-dependent insulinotropic polypeptide/ GLP-1 receptor co-agonist tirzepatide. Diabetes Obes Metab. 2023;25:1361–71.
Article CAS PubMed Google Scholar
Sattar N, McGuire DK, Pavo I, Weerakkody GJ, Nishiyama H, Wiese Russell J and Zoungas S. Tirzepatide cardiovascular event risk assessment: a pre-specified meta-analysis. Nat Med. 2022;28:591–8. An analysis of effect of tirzepatide on cardiovascular risk factors across randomised controlled trials.
Bucheit J, Ayers J, Pamulapati L, Browning A, Sisson E. A novel dual incretin agent, tirzepatide (LY3298176), for the treatment of type 2 diabetes mellitus and cardiometabolic health. J Cardiovasc Pharmacol. 2022;80:171–9.
Article CAS PubMed Google Scholar
Wilson JM, Lin Y, Luo MJ, Considine G, Cox AL, Bowsman LM, et al. The dual glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1 receptor agonist tirzepatide improves cardiovascular risk biomarkers in patients with type 2 diabetes: a post hoc analysis. Diabetes Obes Metab. 2021;24:148–53.
Article PubMed PubMed Central Google Scholar
Wilson JM, Nikooienejad A, Robins Deborah A, Roell WC, Riesmeyer JS, Haupt A, Duffin KL, et al. The dual glucose-dependent insulinotropic peptide and glucagon-like peptide-1 receptor agonist, tirzepatide, improves lipoprotein biomarkers associated with insulin resistance and cardiovascular risk in patients with type 2 diabetes. Diabetes Obes Metab. 2020;22:2451–9.
Article CAS PubMed PubMed Central Google Scholar
Rosenstock J, Wysham C, Frías JP, Kaneko S, Lee CJ, Fernández Landó L, et al. Efficacy and safety of a novel dual GIP and GLP-1 receptor agonist tirzepatide in patients with type 2 diabetes (SURPASS-1): a double-blind, randomised, phase 3 trial. The Lancet. 2021;398:143–55. Phase 3 randomized controlled clinical trial on tirzepatide in the treatment of type 2 diabetes.
Frias JP, Davies MJ, Julio Rosenstock, Pérez Manghi FC, Fernández Landó L, Bergman BK, Liu B, et al. Tirzepatide versus semaglutide once weekly in patients with type 2 diabetes. N Engl J Med. 2021;385:503–15.
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