Profile of Semaglutide in the Management of Type 2 Diabetes: Design, Development, and Place in Therapy

Overview

Journal Drug Des Devel Ther

Specialty Pharmacology

Date 2019 Mar 14

PMID 30863012

Citations 8

Authors

Fernando Gomez-Peralta

Cristina Abreu

Affiliations

Soon will be listed here.

Abstract

Type 2 diabetes mellitus (T2DM) has become one of the leading causes of morbidity and mortality in developed countries. Low efficacy, weight gain, and hypoglycemia are the main pitfalls of previous treatments for T2DM. New therapies have been designed with the aim of improving the results in efficacy and quality of life. Glucagon-like peptide 1 (GLP-1) receptor agonists (GLP-1 RA) increase glucose-dependent insulin secretion, decrease gastric emptying, and reduce postprandial glucagon secretion. The last GLP-1 RA approved by the US Food and Drug Administration and European Medicines Agency was semaglutide. This review describes its pharmacology, core clinical data coming from the randomized controlled trials included in the development program, proven cardiovascular benefits, safety issues, and precautions for the use of semaglutide in special populations. Additionally, an overview of the positioning of semaglutide in T2DM therapy and practical issues regarding semaglutide initiation are offered.

Citing Articles

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References

Chico A, Vidal-Rios P, Subira M, Novials A . The continuous glucose monitoring system is useful for detecting unrecognized hypoglycemias in patients with type 1 and type 2 diabetes but is not better than frequent capillary glucose measurements for improving metabolic control. Diabetes Care. 2003; 26(4):1153-7. DOI: 10.2337/diacare.26.4.1153. View

Aroda V, Ratner R . The safety and tolerability of GLP-1 receptor agonists in the treatment of type 2 diabetes: a review. Diabetes Metab Res Rev. 2011; 27(6):528-42. DOI: 10.1002/dmrr.1202. View

Budnitz D, Lovegrove M, Shehab N, Richards C . Emergency hospitalizations for adverse drug events in older Americans. N Engl J Med. 2011; 365(21):2002-12. DOI: 10.1056/NEJMsa1103053. View

Smith-Spangler C, Bhattacharya J, Goldhaber-Fiebert J . Diabetes, its treatment, and catastrophic medical spending in 35 developing countries. Diabetes Care. 2012; 35(2):319-26. PMC: 3263916. DOI: 10.2337/dc11-1770. View

McCoy R, Van Houten H, Ziegenfuss J, Shah N, Wermers R, Smith S . Increased mortality of patients with diabetes reporting severe hypoglycemia. Diabetes Care. 2012; 35(9):1897-901. PMC: 3425008. DOI: 10.2337/dc11-2054. View

Mari A, Bagger J, Ferrannini E, Holst J, Knop F, Vilsboll T . Mechanisms of the incretin effect in subjects with normal glucose tolerance and patients with type 2 diabetes. PLoS One. 2013; 8(9):e73154. PMC: 3760909. DOI: 10.1371/journal.pone.0073154. View

Gomez-Peralta F, Abreu Padin C . Do we need new treatments for type 2 diabetes?. Endocrinol Nutr. 2014; 61(6):323-8. DOI: 10.1016/j.endonu.2013.10.013. View

Balkau B, Home P, Vincent M, Marre M, Freemantle N . Factors associated with weight gain in people with type 2 diabetes starting on insulin. Diabetes Care. 2014; 37(8):2108-13. DOI: 10.2337/dc13-3010. View

Kapitza C, Nosek L, Jensen L, Hartvig H, Jensen C, Flint A . Semaglutide, a once-weekly human GLP-1 analog, does not reduce the bioavailability of the combined oral contraceptive, ethinylestradiol/levonorgestrel. J Clin Pharmacol. 2014; 55(5):497-504. PMC: 4418331. DOI: 10.1002/jcph.443. View

10.

Barranco R, Gomez-Peralta F, Abreu C, Delgado M, Palomares R, Romero F . Incidence and care-related costs of severe hypoglycaemia requiring emergency treatment in Andalusia (Spain): the PAUEPAD project. Diabet Med. 2015; 32(11):1520-6. PMC: 4755037. DOI: 10.1111/dme.12843. View

11.

Lau J, Bloch P, Schaffer L, Pettersson I, Spetzler J, Kofoed J . Discovery of the Once-Weekly Glucagon-Like Peptide-1 (GLP-1) Analogue Semaglutide. J Med Chem. 2015; 58(18):7370-80. DOI: 10.1021/acs.jmedchem.5b00726. View

12.

Nauck M, Petrie J, Sesti G, Mannucci E, Courreges J, Lindegaard M . A Phase 2, Randomized, Dose-Finding Study of the Novel Once-Weekly Human GLP-1 Analog, Semaglutide, Compared With Placebo and Open-Label Liraglutide in Patients With Type 2 Diabetes. Diabetes Care. 2015; 39(2):231-41. DOI: 10.2337/dc15-0165. View

13.

Gomez Huelgas R, Gomez Peralta F, Carrillo Fernandez L, Galve E, Casanueva F, Puig Domingo M . Position statement of the SEMI, SED, redGDPS, SEC, SEEDO, SEEN, SEMERGEN y SEMFYC. Rev Clin Esp (Barc). 2015; 215(9):505-14. DOI: 10.1016/j.rce.2015.07.003. View

14.

Ting D, Cheung G, Wong T . Diabetic retinopathy: global prevalence, major risk factors, screening practices and public health challenges: a review. Clin Exp Ophthalmol. 2015; 44(4):260-77. DOI: 10.1111/ceo.12696. View

15.

Marso S, Bain S, Consoli A, Eliaschewitz F, Jodar E, Leiter L . Semaglutide and Cardiovascular Outcomes in Patients with Type 2 Diabetes. N Engl J Med. 2016; 375(19):1834-1844. DOI: 10.1056/NEJMoa1607141. View

16.

. Global, regional, and national disability-adjusted life-years (DALYs) for 315 diseases and injuries and healthy life expectancy (HALE), 1990-2015: a systematic analysis for the Global Burden of Disease Study 2015. Lancet. 2016; 388(10053):1603-1658. PMC: 5388857. DOI: 10.1016/S0140-6736(16)31460-X. View

17.

Sorli C, Harashima S, Tsoukas G, Unger J, Karsbol J, Hansen T . 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 3a trial. Lancet Diabetes Endocrinol. 2017; 5(4):251-260. DOI: 10.1016/S2213-8587(17)30013-X. View

18.

Blundell J, Finlayson G, Axelsen M, Flint A, Gibbons C, Kvist T . Effects of once-weekly semaglutide on appetite, energy intake, control of eating, food preference and body weight in subjects with obesity. Diabetes Obes Metab. 2017; 19(9):1242-1251. PMC: 5573908. DOI: 10.1111/dom.12932. View

19.

Jensen L, Helleberg H, Roffel A, Van Lier J, Bjornsdottir I, Pedersen P . Absorption, metabolism and excretion of the GLP-1 analogue semaglutide in humans and nonclinical species. Eur J Pharm Sci. 2017; 104:31-41. DOI: 10.1016/j.ejps.2017.03.020. View

20.

Aroda V, Bain S, Cariou B, Piletic M, Rose L, Axelsen M . 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,.... Lancet Diabetes Endocrinol. 2017; 5(5):355-366. DOI: 10.1016/S2213-8587(17)30085-2. View