#PAGE_PARAMS# #ADS_HEAD_SCRIPTS# #MICRODATA#

Oral semaglutide: the future of GLP1 receptor agonism?


Authors: Matej Samoš;  Marián Mokáň
Authors‘ workplace: I. interná klinika JLF UK a UNM, Martin
Published in: Forum Diab 2021; 10(3): 213-217
Category:

Overview

Semaglutide is a modern anti-diabetic agent acting as a glucagon like peptide 1 receptor agonist (GLP-1 RA). GLP-1 RA therapy improves glycemic control, significantly reduces body weight, and improves blood pressure control and blood lipid levels, together with low risk of hypoglycemia. Moreover, this therapy protects against atherogenesis and has a proven cardiovascular and nephroprotective benefit and a protective effect on pancreatic B-cells function. According to current recommendations, GLP-1 RA therapy should be preferred in diabetic patients with high cardiovascular risk or with already existing atherosclerotic cardiovascular disease; nevertheless, this recommendations could not be fully adopted due to a need for drug subcutaneous application. Oral semaglutide is the first oral GLP-1 RA with real possibility of clinical use. This article summarizes the current knowledge about oral semaglutide, about its effect on glycemic control and data regarding its cardiovascular safety from currently available clinical trials.

Keywords:

compliance – type 2 diabetes mellitus – GLP1 receptor agonists – oral semaglutide


Sources

1. Mokáň M, Galajda P. Kardioprotektívny efekt liečby GLP-1 analógmi vo svetle výsledkov najnovších klinických štúdií. Forum Diab 2021; 10(2): 108–113.

2. Tkáč I. Agonisty GLP1-receptorov: antidiabetiká s antiaterogénnym účinkom. AtheroRev 2020; 5(3): 181–184.

3. Cosentino F, Grant PJ, Aboyans V et al. [ESC Scientific Document Group]. 2019 ESC Guidelines on diabetes, pre-diabetes, and cardiovascular diseases developed in collaboration with the EASD. Eur Heart J 2020; 41(2): 255–323. Dostupné z DOI: <http://dx.doi.org/10.1093/eurheartj/ehz486>.

4. Davies MJ, D’Alessio DA, Fradkin J et al. Management of Hyperglycemia in Type 2 Diabetes, 2018. A Consensus Report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Diabetes Care 2018; 41(12): 2669–2701. Dostupnéz DOI: <http://dx.doi.org/10.2337/dci18–0033>.

5. Buse JB, Wexler DJ, Tsapas A et al. 2019 Update to: Management of Hyperglycemia in Type 2 Diabetes, 2018. A Consensus Report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Diabetes Care 2020; 43(2): 487–493. Dostupné z DOI: <http://dx.doi.org/10.2337/dci19–0066>.

6. Aroda VR, Rosenstock J, Terauchi Y et al. [PIONEER 1 Investigators]. PIONEER 1: Randomized Clinical Trial of the Efficacy and Safety of Oral Semaglutide Monotherapy in Comparison With Placebo in Patients With Type 2 Diabetes. Diabetes Care 2019; 42(9): 1724–1732. Dostupné z DOI: <http://dx.doi.org/10.2337/dc19–0749>.

7. Bucheit JD, Pamulapati LG, Carter N et al. Oral Semaglutide: A Review of the First Oral Glucagon-Like Peptide 1 Receptor Agonist. Diabetes Technol Ther 2020; 22(1): 10–18. Dostupné z DOI: <http://dx.doi.org/10.1089/dia.2019.0185>.

8. Sorli C, Harashima SI, Tsokas GM et al. Efficacy and safety of once-weekly semaglutide monotherapy versus placebo in patients with type 2 diabetes (SUSTAIN 1): a double-blind, randomised, placebo-controlled, parallel-group, multinational, multicentre phase 3atrial. Lancet Diabetes Endocrinol 2017; 5(4): 251–260. Dostupné z DOI:<http://dx.doi.org/10.1016/S2213–8587(17)30013-X>.

9. Ahren B, Masmiquel L, Kumar H et al. Efficacy and safety of once-weekly semaglutide versus once-daily sitagliptin as an add-on to metformin, thiazolidinediones, or both, in patients with type 2 diabetes (SUSTAIN 2): a 56-week, double-blind, phase 3a, randomised trial. Lancet Diabetes Endocrinol 2017; 5(5): 341–354. Dostupné z DOI:<http://dx.doi.org/10.1016/S2213–8587(17)30092-X>.

10. Ahmann AJ, Capehorn M, Charpentier G et al. Efficacy and safety of once-weekly semaglutide versus exenatide ER in subjects with type 2 diabetes (SUSTAIN 3): A 56-week, open-label, randomized clinical trial. Diabetes Care 2018; 41(2): 258–266. Dostupné z DOI: <http://dx.doi.org/10.2337/dc17–0417>.

11. Aroda VR, Bain SC, Cariou B et al. Efficacy and safety of once-weekly semaglutide versus once-daily insulin glargine as add-on to metformin (with or without sulfonylureas) in insulin-naive patients with type 2 diabetes (SUSTAIN 4): a randomised, open-label, parallel-group, multicentre, multinational, phase 3a trial. Lancet Diabetes Endocrinol 2017; 5(5): 355–366. Dostupné z DOI:<http://dx.doi.org/10.1016/S2213–8587(17)30085–2>.

12. Rodbard HW, Lingvay I, Reed J et al. Semaglutide added to basal insulin in type 2 diabetes (SUSTAIN 5): A randomized, controlled trial. J Clin Endocrinol Metab 2018; 103(6): 2291–2301. Dostupné z DOI:<http://dx.doi.org/10.1210/jc.2018–00070>.

13. Marso SP, Bain SC, Consoli A et al. SUSTAIN-6 Investigators. Semaglutide and cardiovascular outcomes in patients with type 2 diabetes. N Engl J Med 2016; 375(19): 1834–1844. Dostupné z DOI: <http://dx.doi.org/10.1056/NEJMoa1607141>.

14. Pratley RE, Aroda VR, Lingvay I et al. Semaglutide versus dulaglutide once weekly in patients with type 2 diabetes (SUSTAIN 7): a randomised, open-label, phase 3b trial. Lancet Diabetes Endocrinol 2018; 6(4): 275–228. Dostupné z DOI: <http://dx.doi.org/10.1016/S2213–8587(18)30024-X>.

15. Lingvay I, Catarig AM, Frias JP et al. Efficacy and safety of once-weekly semaglutide versus daily canagliflozin as add-on to metformin in patients with type 2 diabetes (SUSTAIN 8): a double-blind, phase 3b, randomised controlled trial. Lancet Diabetes Endocrinol 2019; 7(11): 834–844. Dostupné z DOI: <http://dx.doi.org/10.1016/S2213–8587(19)30311–0>.

16. Zinman B, Bhosekar V, Busch R et al. Semaglutide once weekly as add-on to SGLT-2 inhibitor therapy in type 2 diabetes (SUSTAIN 9): a randomised, placebo-controlled trial. Lancet Diabetes Endocrinol 2019; 7(5): 356–367. Dostupné z DOI: <http://dx.doi.org/10.1016/S2213–8587(19)30066-X.

17. Capehorn MS, Catarig AM, Furberg JK et al. Efficacy and safety of once-weekly semaglutide 1.0mg vs once-daily liraglutide 1.2mg as add-on to 1–3 oral antidiabetic drugs in subjects with type 2 diabetes (SUSTAIN 10). Diabetes Metab 2020; 46(2): 100–109. Dostupné z DOI:<http://dx.doi.org/10.1016/j.diabet.2019.101117>.

18. Rybelsus. Súhrn charakteristických vlastností lieku. Dostupné z WWW: <https://www.ema.europa.eu/en/documents/product-information/rybelsus-epar-product-information_sk.pdf>.

19. Aroda VR, Rosenstock J, Terauchi Y et al. [PIONEER 1 Investigators]. PIONEER 1: Randomized Clinical Trial of the Efficacy and Safety of Oral Semaglutide Monotherapy in Comparison With Placebo in Patients With Type 2 Diabetes. Diabetes Care 2019; 42(9): 1724–1732. Dostupné z DOI: <http://dx.doi.org/10.2337/dc19–0749>.

20. Rodbard HW, Rosenstock J, Canani LH et al. [PIONEER 2 Investigators]. Oral Semaglutide Versus Empagliflozin in Patients With Type 2 Diabetes Uncontrolled on Metformin: The PIONEER 2 Trial. Diabetes Care 2019; 42(12): 2272–2281. Dostupné z DOI: <http://dx.doi.org/10.2337/dc19–0883>.

21. Rosenstock J, Allison D, Birkenfeld AL et al. [PIONEER 3 Investigators]. Effect of Additional Oral Semaglutide vs Sitagliptin on Glycated Hemoglobin in Adults With Type 2 Diabetes Uncontrolled With Metformin Alone or With Sulfonylurea: The PIONEER 3 Randomized Clinical Trial. JAMA 2019; 321(15): 1466–1480. Dostupné z DOI: <http://dx.doi.org/10.1001/jama.2019.2942>.

22. Pratley R, Amod A, Hoff ST et al. [PIONEER 4 investigators]. Oral semaglutide versus subcutaneous liraglutide and placebo in type 2 diabetes (PIONEER 4): a randomised, double-blind, phase 3a trial. Lancet 2019; 394(10192): 39–50. Dostupné z DOI: <http://dx.doi.org/10.1016/S0140–6736(19)31271–1>.

23. Mosenzon O, Blicher TM, Rosenlund S et al. [PIONEER 5 Investigators]. Efficacy and safety of oral semaglutide in patients with type 2 diabetes and moderate renal impairment (PIONEER 5): a placebo-controlled, randomised, phase 3a trial. Lancet Diabetes Endocrinol 2019; 7: 515–527. Dostupné z DOI: <http://dx.doi.org/10.1016/S2213–8587(19)30192–5>.

24. Zinman B, Aroda VR, Buse JB et al. [PIONEER 8 Investigators]. Efficacy, Safety, and Tolerability of Oral Semaglutide Versus Placebo Added to Insulin With or Without Metformin in Patients With Type 2 Diabetes: The PIONEER 8 Trial. Diabetes Care 2019; 42(12): 2262–2271. Dostupné z DOI: <http://dx.doi.org/10.2337/dc19–0898>.

25. Husain M, Birkenfeld AL, Donsmark M et al. [PIONEER 6 Investigators]. Oral Semaglutide and Cardiovascular Outcomes in Patients with Type 2 Diabetes. N Engl J Med 2019; 381: 841–851. Dostupné z DOI: <http://dx.doi.org/10.1056/NEJMoa1901118>.

26. Husain M, Bain SC, Jeppesen OK et al. Semaglutide (SUSTAIN and PIONEER) reduces cardiovascular events in type 2 diabetes across varying cardiovascular risk. Diabetes Obes Metab 2020; 22(3): 442–451. Dostupné z DOI: <http://dx.doi.org/10.1111/dom.13955>.

Labels
Diabetology Endocrinology Internal medicine
Topics Journals
Login
Forgotten password

Enter the email address that you registered with. We will send you instructions on how to set a new password.

Login

Don‘t have an account?  Create new account

#ADS_BOTTOM_SCRIPTS#