The emerging role of GLP-1 receptor agonists in treating or preventing cancer

Abstract

With the growing incidence of obesity-related malignancies, glucagon-like peptide-1 (GLP-1) receptor agonists represent an intriguing potential clinical avenue for cancer prevention and treatment. Population-based data suggest that individuals who have taken GLP-1 receptor agonists have a decreased incidence of obesity-related cancers. Moreover, in vivo and in vitro studies have demonstrated the antitumor activity of these agents independent of other antineoplastic therapeutics. Additionally, other pre-clinical studies have shown that GLP-1 receptor agonists may help overcome resistance to chemotherapy-refractory cancer cells, thus demonstrating a plausible role in cancer treatment. Randomized controlled trials utilizing GLP-1 receptor agonists in both cancer prevention and treatment may allow for a better understanding of the role of these agents in modern oncology.

Keywords

GLP-1 receptor agonist / cancer / prevention / resistance

References

[1] Drucker DJ.Mechanisms of action and therapeutic application of glucagon-like peptide-1.Cell Metab2018;27:740-56

[2] Rubinstein MM,Iyengar NM.Targeting obesity-related dysfunction in hormonally driven cancers.Br J Cancer2021;125:495-509 PMCID:PMC8368182

[3] Nauck MA, Jensen TJ, Rosenkilde C, Calanna S, Buse JB; LEADER Publication Committee on behalf of the LEADER Trial Investigators. Neoplasms reported with liraglutide or placebo in people with type 2 diabetes: results from the LEADER randomized trial. Diabetes Care 2018;41:1663-71. PMCID:PMC6463597

[4] Nomiyama T,Irie S.Exendin-4, a GLP-1 receptor agonist, attenuates prostate cancer growth.Diabetes2014;63:3891-905

[5] Arvanitakis K,Kotsa K.How far beyond diabetes can the benefits of glucagon-like peptide-1 receptor agonists go?.Cancers2022;14:4651 PMCID:PMC9562923

[6] Kosowska A,Garczorz W.Exenatide modulates tumor-endothelial cell interactions in human ovarian cancer cells.Endocr Connect2017;6:856-65 PMCID:PMC5682419

[7] Madsen MSA,Pallejà A.Metabolic and gut microbiome changes following GLP-1 or dual GLP-1/GLP-2 receptor agonist treatment in diet-induced obese mice.Sci Rep2019;9:15582 PMCID:PMC6821799

[8] Dizman N,Bergerot P.Nivolumab plus ipilimumab with or without live bacterial supplementation in metastatic renal cell carcinoma: a randomized phase 1 trial.Nat Med2022;28:704-12 PMCID:PMC9018425

[9] Trakoonsenathong R,Aphivatanasiri C.Liraglutide exhibits potential anti-tumor effects on the progression of intrahepatic cholangiocarcinoma, in vitro and in vivo.Sci Rep2024;14:13726 PMCID:PMC11178799

[10] Wang L,Kaelber DC,Berger NA.GLP-1 receptor agonists and colorectal cancer risk in drug-naive patients with type 2 diabetes, with and without overweight/obesity.JAMA Oncol2024;10:256-8 PMCID:PMC10704339

[11] Wang L,Kaelber DC.Glucagon-like peptide 1 receptor agonists and 13 obesity-associated cancers in patients with type 2 diabetes.JAMA Netw Open2024;7:e2421305 PMCID:PMC11227080

[12] Zhao HJ,Hu LJ.Activation of GLP-1 receptor enhances the chemosensitivity of pancreatic cancer cells.J Mol Endocrinol2020;64:103-13

[13] Nørgaard CH,Hansen CT.Treatment with glucagon-like peptide-1 receptor agonists and incidence of dementia: data from pooled double-blind randomized controlled trials and nationwide disease and prescription registers.Alzheimers Dement2022;8:e12268 PMCID:PMC8864443

[14] Benjamin DJ,Prasad V.Cardiovascular/anti-inflammatory drugs repurposed for treating or preventing cancer: a systematic review and meta-analysis of randomized trials.Cancer Med2024;13:e7049 PMCID:PMC10943275

[15] Wang YB,Luo L.Immortal time bias exaggerates the effect of metformin on the risk of gastric cancer: a meta-analysis.Pharmacol Res2021;165:105425