Should Incretin Agonist-Based Brugs be Considered for First Line Antihypertensive Therapy?

Danser AHJ, Deinum J. Antihypertensive drug treatment: are we ready for the future? J Hypertens 1 Juli. 2025;43(7):1099–107. 10. 1097/HJH.0000000000004019 PubMed PMID: 40167023.

Article  CAS  Google Scholar 

Drucker DJ. GLP-1-based therapies for diabetes, obesity and beyond. Nat Rev Drug Discov August. 2025;24(8):631–50. https://doi.org/10.1038/s41573-025-01183-8.

Article  CAS  Google Scholar 

Rosen CJ, Ingelfinger JR. GLP-1 Receptor Agonists. New Engl J Med 1 April. 2026;394(13):1313–24. https://doi.org/10.1056/NEJMra2500106.

Article  CAS  Google Scholar 

Dreher L, Kylies D, Danser AHJ, Wenzel UO, Incretin-based therapies. A paradigm shift in blood pressure management? Hypertens Juli. 2025;82(7):1167–74. https://doi.org/10.1161/HYPERTENSIONAHA.125. .25112 PubMed PMID: 40406862.

Article  CAS  Google Scholar 

Sattar N, Lee MMY. Estimating direct tissue effects versus weight loss effects of incretin-based drugs for obesity on various chronic conditions. Lancet Diabetes Endocrinol April. 2025;13(4):347–54. https://doi.org/10.1016/S2213-8587(. 24)00363-2 PubMed PMID: 39870097.

Article  CAS  Google Scholar 

Chen J, Cooper M, Coughlan M. Renoprotective mechanisms of glucagon-like peptide-1 receptor agonists. Diabetes Metabolism 1 Mai. 2025;51(3):101641. https://doi.org/10.1016/j.diabet.2025.101641.

Article  CAS  Google Scholar 

Ribeiro-Silva JC, Tavares CAM, Girardi ACC. The blood pressure lowering effects of glucagon-like peptide-1 receptor agonists: a mini-review of the potential mechanisms. Curr Opin Pharmacol April. 2023;69:102355. https://doi.org/10.1016/j.coph.2023.102355. PubMed PMID: 36857807.

Article  CAS  Google Scholar 

Harrison DG, Coffman TM, Wilcox CS. Pathophysiology of hypertension: the mosaic theory and beyond. Circ Res 2 April. 2021;128(7):847–63. 10. 1161/CIRCRESAHA.121.318082.

Article  CAS  Google Scholar 

Hengel FE, Benitah JP, Wenzel UO. Mosaic theory revised: inflammation and salt play central roles in arterial hypertension. Cell Mol Immunol Mai. 2022;19(5):561–76. https://doi.org/10.1038/s41423-022-00851-8 . PubMed PMID: 35354938; PubMed Central PMCID: PMC9061754.

Article  CAS  Google Scholar 

Touyz RM, Feldman RD, Harrison DG, Schiffrin EL. A New Look At the Mosaic Theory of Hypertension. Can J Cardiol Mai. 2020;36(5):591–2. https://doi.org/10.1016/j.cjca.2020.03.025 . PubMed PMID: 32389334; PubMed Central PMCID: PMC9127785.

Article  Google Scholar 

Göke R, Larsen PJ, Mikkelsen JD, Sheikh SP. Distribution of GLP-1 binding sites in the rat brain: evidence that exendin-4 is a ligand of brain GLP-1 binding sites. Eur J Neurosci 1 November. 1995;7(11):2294–300. https://doi.org/10.1111/j.1460-9568.1995.tb00650. x PubMed PMID: 8563978.

Article  Google Scholar 

Katsurada K, Nakata M, Saito T, Zhang B, Maejima Y, Nandi SS. u. a. Central Glucagon-like Peptide-1 Receptor Signaling via Brainstem Catecholamine Neurons Counteracts Hypertension in Spontaneously Hypertensive Rats. Sci Rep 19 September. 2019;9(1):12986. https://doi.org/10.1038/s41598-019-49364-x . PubMed PMID: 31537818; PubMed Central PMCID: PMC6753091.

Article  CAS  Google Scholar 

Daniels D, Mietlicki-Baase EG. Glucagon-Like Peptide 1 in the brain: whereis it coming from, where is it going? Diabetes Januar 2019;68(1):15–7. https://doi.org/10.2337/dbi18-0045 PubMed PMID: 30573675; PubMed Central PMCID: PMC6302532.

Article  CAS  Google Scholar 

Helmstädter J, Frenis K, Filippou K, Grill A, Dib M, Kalinovic S. u. a. Endothelial GLP-1 (Glucagon-Like Peptide-1) Receptor mediates cardiovascular protection by liraglutide in mice with experimental arterial hypertension. Arterioscler Thromb Vasc Biol Januar. 2020;40(1):145–58. https://doi.org/10.1161/atv.0000615456.97862.30. PubMed PMID: 31747801; PubMed Central PMCID: PMC6946108.

Article  CAS  Google Scholar 

Luo X, Hu Y, He S, Ye Q, Lv Z, Liu J. u. a. Dulaglutide inhibits high glucose- induced endothelial dysfunction and NLRP3 inflammasome activation. Arch Biochem Biophys 15 August. 2019;671:203–9. .008 PubMed PMID: 31302140.

Article  CAS  Google Scholar 

Fan SH, Xiong QF, Wang L, Zhang LH, Shi YW. Glucagon-like peptide 1 treatment reverses vascular remodelling by downregulating matrix metalloproteinase 1 expression through inhibition of the ERK1/2/NF-κB signalling pathway. Mol Cell Endocrinol 1 Dezember. 2020;518:111005. https://doi.org/10.1016/j.mce.2020.111005 . PubMed PMID: 32877753.

Article  CAS  Google Scholar 

Gutzwiller JP, Tschopp S, Bock A, Zehnder CE, Huber AR, Kreyenbuehl M. u. a. Glucagon-like peptide 1 induces natriuresis in healthy subjects and in insulin-resistant obese men. J Clin Endocrinol Metab Juni. 2004;89(6):3055–61. https://doi.org/10.1210/jc.2003-031403 . PubMed PMID: 15181098.

Article  CAS  Google Scholar 

Perkovic V, Tuttle KR, Rossing P, Mahaffey KW, Mann JFE, Bakris G. u. a. Effects of semaglutide on chronic kidney disease in patients with type 2 diabetes. New Engl J Med 10 Juli. 2024;391(2):109–21. https://doi.org/10.1056/NEJMoa2403347.

Article  CAS  Google Scholar 

Briones AM, Nguyen Dinh Cat A, Callera GE, Yogi A, Burger D, He Y. u. a. Adipocytes produce aldosterone through calcineurin-dependent signaling pathways: implications in diabetes mellitus-associated obesity and vascular dysfunction. Hypertens Mai. 2012;59(5):1069–78. https://doi.org/10.1161/HYPERTENSIONAHA.111.190223 . PubMed PMID: 22493070.

Article  CAS  Google Scholar 

Dinh Cat AN, Friederich-Persson M, White A, Touyz RM. Adipocytes, aldosterone and obesity-related hypertension. J Mol Endocrinol Juli. 2016;57(1):F7–21. https://doi.org/10.1530/JME-16-0025 . PubMed PMID: 27357931.

Article  CAS  Google Scholar 

Huby AC, Antonova G, Groenendyk J, Gomez-Sanchez CE, Bollag WB, Filosa JA. u. a. Adipocyte-derived hormone leptin is a direct regulator of aldosterone secretion, which promotes endothelial dysfunction and cardiac fibrosis. Circulation 1 Dezember. 2015;132(22):2134–45. 10.1161. /CIRCULATIONAHA.115.018226 PubMed PMID: 26362633.

Article  CAS  Google Scholar 

Huby AC, Otvos L, Belin de Chantemèle EJ. Leptin induces hypertension and endothelial dysfunction via aldosterone-dependent mechanisms in obese female mice. Hypertens Mai. 2016;67(5):1020–8. https://doi.org/10.1161/HYPERTENSIONAHA.115.06642. PubMed PMID: 26953321; PubMed Central PMCID: PMC5088432.

Article  CAS  Google Scholar 

Hall ME, Omoto ACM, Hall JE, Obesity. Fatty Kidney, and hypertension: potential role of aldosterone. Hypertens November. 2025;82(11):1822–5. https://doi.org/10.1161/HYPERTENSIONAHA.125.25627. PubMed PMID: 41091904.

Article  CAS  Google Scholar 

Chen X, Mao Y, Hu J, Han S, Gong L, Luo T. u. a. Perirenal fat thickness is significantly associated with the risk for development of chronic kidney disease in patients with diabetes. Diabetes Oktober. 2021;70(10):2322–32. https://doi.org/10.2337/db20-1031. 1031 PubMed PMID: 34593536.

Article  CAS  Google Scholar 

Foster MC, Hwang SJ, Porter SA, Massaro JM, Hoffmann U, Fox CS. Fatty kidney, hypertension, and chronic kidney disease: the Framingham Heart Study. Hypertens November. 2011;58(5):784–90. https://doi.org/10.1161/HYPERTENSIONAHA.111.175315 . PubMed PMID: 21931075; PubMed Central PMCID: PMC3204377.

Article  CAS  Google Scholar 

Cooper ME, van Raalte DH. GLP-1 agonists in the treatment of chronic kidney disease in type 2 diabetes and obesity. J Clin Invest. 2025;135(21):e194749. https://doi.org/10.1172/JCI194749.

Cherney DZI, Belmar N, Bjornstad P, Chacko MM, Gunnarsson TP, Hodgin JB. u. a. Rationale, design and baseline characteristics of REMODEL, a mechanism-of-action trial with semaglutide in people with type 2 diabetes and chronic kidney disease. Nephrol Dial Transpl 30 Oktober. 2025;40(11):2182–92. https://doi.org/10.1093/ndt/gfaf. 114 PubMed PMID: 40608494; PubMed Central PMCID: PMC12559791.

Article  Google Scholar 

Apperloo EM, Tuttle KR, Pavo I, Haupt A, Taylor R, Wiese RJ. u. a. Tirzepatide associated with reduced albuminuria in participants with type 2 diabetes: pooled post hoc analysis from the randomized active- and placebo-controlled SURPASS-1-5 clinical trials. Diabetes Care 1 März. 2025;48(3):430–6. https://doi.org/10.2337/dc24-1773. 1773 PubMed PMID: 39746157; PubMed Central PMCID: PMC11870291.

Article  CAS  Google Scholar 

Bae JH. SGLT2 Inhibitors and GLP-1 Receptor agonists in diabetic kidney disease: evolving evidence and clinical application. Diabetes Metab J Mai. 2025;49(3):386–402. https://doi.org/10.4093/dmj.2025.0220. PubMed PMID: 40367988; PubMed Central PMCID: PMC12086580.

Article  Google Scholar 

Krumholz HM, de Lemos JA, Sattar N, Linetzky B, Sharma P, Mast CJ. u. a. Tirzepatide and blood pressure reduction: stratified analyses of the SURMOUNT-1 randomised controlled trial. Heart 16 September. 2024;110(19):1165–71. https://doi.org/10.1136/heartjnl-2024-324170 . PubMed PMID: 39084707; PubMed Central PMCID: PMC11420724.

Article  CAS  Google Scholar 

Kennedy C, Hayes P, Cicero AFG, Dobner S, Le Roux CW. McEvoy JW, u. a. Semaglutide and blood pressure: an individual patient data meta-analysis. Eur Heart J 1 September. 2024;45(38):4124–34. https://doi.org/10.1093/eurheartj/ehae564 . PubMed PMID: 39217502; PubMed Central PMCID: PMC11458150.

Article  CAS  Google Scholar 

Aronne LJ, Horn DB, Roux CW le, Ho W, Falcon BL, Valderas EG et al. Juli. Tirzepatide as compared with semaglutide for the treatment of obesity. N Engl J Med. 2025;393(1):26–36. https://doi.org/10.1056/NEJMoa2416394

Article  CAS  PubMed  Google Scholar 

Garvey WT, Blüher M, Osorto Contreras CK, Davies MJ, Winning Lehmann E, Pietiläinen KH. u. a. Coadministered cagrilintide and semaglutide in adults with overweight or obesity. N Engl J Med 14 August. 2025;393(7):635–47. doi:10.1056/NEJMoa2502081 PubMed PMID: 40544433.

Article 

Comments (0)

No login
gif