Skip to main content
Top
Published in: Advances in Therapy 10/2020

Open Access 01-10-2020 | Sitagliptin | Review

Oral Semaglutide, A New Option in the Management of Type 2 Diabetes Mellitus: A Narrative Review

Authors: Areti Sofogianni, Konstantinos Tziomalos

Published in: Advances in Therapy | Issue 10/2020

Login to get access

Abstract

According to current guidelines, glucagon-like peptide-1 (GLP-1) receptor agonists are the antidiabetic agent of choice in patients with type 2 diabetes mellitus (T2DM) and established cardiovascular disease (CVD) and are also the preferable antidiabetic agent in patients with T2DM without CVD but with indicators of high cardiovascular risk. A limitation in the use of GLP-1 receptor agonists is that they are delivered by subcutaneous injections. In this context, the development of an orally administered formulation of semaglutide offers an additional option in the management of patients with T2DM. In the present review, we discuss the findings of the main trials that evaluated the safety and efficacy of oral semaglutide. Oral semaglutide appears to be more effective in reducing HbA1c levels and body weight than other antidiabetic agents and similarly effective to other GLP-1 receptor agonists. The safety profile of oral semaglutide is also comparable with other members of its class. Even though oral semaglutide did not reduce the incidence of the composite primary endpoint in a randomized controlled trial, a reduction in cardiovascular and all-cause mortality was observed. Therefore, oral semaglutide appears to represent a useful tool in the management of patients with TD2M, particularly those with established CVD or high cardiovascular risk and unwilling to receive injectable GLP-1 receptor agonists.
Literature
1.
go back to reference Buse JB, Wexler DJ, Tsapas A, et al. Update to: management of hyperglycaemia in type 2 diabetes, 2018. A consensus report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Diabetologia. 2019;(63):221–8.CrossRef Buse JB, Wexler DJ, Tsapas A, et al. Update to: management of hyperglycaemia in type 2 diabetes, 2018. A consensus report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Diabetologia. 2019;(63):221–8.CrossRef
2.
go back to reference Marso SP, Daniels GH, Brown-Frandsen K, LEADER Steering Committee, LEADER Trial Investigators, et al. Liraglutide and cardiovascular outcomes in type 2 diabetes. N Engl J Med. 2016;375:311–22.CrossRef Marso SP, Daniels GH, Brown-Frandsen K, LEADER Steering Committee, LEADER Trial Investigators, et al. Liraglutide and cardiovascular outcomes in type 2 diabetes. N Engl J Med. 2016;375:311–22.CrossRef
3.
go back to reference Marso SP, Bain SC, Consoli A, SUSTAIN-6 Investigators, et al. Semaglutide and cardiovascular outcomes in patients with type 2 diabetes. N Engl J Med. 2016;375:1834–44.CrossRef Marso SP, Bain SC, Consoli A, SUSTAIN-6 Investigators, et al. Semaglutide and cardiovascular outcomes in patients with type 2 diabetes. N Engl J Med. 2016;375:1834–44.CrossRef
4.
go back to reference Gerstein HC, Colhoun HM, Dagenais GR, REWIND Investigators, et al. Dulaglutide and cardiovascular outcomes in type 2 diabetes (REWIND): a double-blind, randomized placebo-controlled trial. Lancet. 2019;394:121–30.CrossRef Gerstein HC, Colhoun HM, Dagenais GR, REWIND Investigators, et al. Dulaglutide and cardiovascular outcomes in type 2 diabetes (REWIND): a double-blind, randomized placebo-controlled trial. Lancet. 2019;394:121–30.CrossRef
5.
go back to reference Buckley ST, Bækdal TA, Vegge A, et al. Transcellular stomach absorption of a derivatized glucagon-like peptide-1 receptor agonist. Sci Transl Med. 2018;10:eaar7047.CrossRef Buckley ST, Bækdal TA, Vegge A, et al. Transcellular stomach absorption of a derivatized glucagon-like peptide-1 receptor agonist. Sci Transl Med. 2018;10:eaar7047.CrossRef
6.
go back to reference Twarog C, Fattah S, Heade J, Maher S, Fattal E, Brayden DJ. Intestinal permeation enhancers for oral delivery of macromolecules: a comparison between salcaprozate sodium (SNAC) and sodium caprate (C10). Pharmaceutics. 2019;11:78.CrossRef Twarog C, Fattah S, Heade J, Maher S, Fattal E, Brayden DJ. Intestinal permeation enhancers for oral delivery of macromolecules: a comparison between salcaprozate sodium (SNAC) and sodium caprate (C10). Pharmaceutics. 2019;11:78.CrossRef
7.
go back to reference Riley MG, Castelli MC, Paehler EA. Subchronic oral toxicity of salcaprozate sodium (SNAC) in Sprague-Dawley and Wistar rats. Int J Toxicol. 2009;28:278–93.CrossRef Riley MG, Castelli MC, Paehler EA. Subchronic oral toxicity of salcaprozate sodium (SNAC) in Sprague-Dawley and Wistar rats. Int J Toxicol. 2009;28:278–93.CrossRef
9.
go back to reference Bækdal TA, Borregaard J, Hansen CW, Thomsen M, Anderson TW. Effect of oral semaglutide on the pharmacokinetics of lisinopril, warfarin, digoxin, and metformin in healthy subjects. Clin Pharmacokinet. 2019;58:1193–203.CrossRef Bækdal TA, Borregaard J, Hansen CW, Thomsen M, Anderson TW. Effect of oral semaglutide on the pharmacokinetics of lisinopril, warfarin, digoxin, and metformin in healthy subjects. Clin Pharmacokinet. 2019;58:1193–203.CrossRef
10.
go back to reference Bækdal TA, Breitschaft A, Navarria A, Hansen CW. A randomized study investigating the effect of omeprazole on the pharmacokinetics of oral semaglutide. Expert Opin Drug Metab Toxicol. 2018;14:869–77.CrossRef Bækdal TA, Breitschaft A, Navarria A, Hansen CW. A randomized study investigating the effect of omeprazole on the pharmacokinetics of oral semaglutide. Expert Opin Drug Metab Toxicol. 2018;14:869–77.CrossRef
11.
go back to reference Baekdal TA, Thomsen M, Kupčová V, Hansen CW, Anderson TW. Pharmacokinetics, safety, and tolerability of oral semaglutide in subjects with hepatic impairment. J Clin Pharmacol. 2018;58:1314–23.CrossRef Baekdal TA, Thomsen M, Kupčová V, Hansen CW, Anderson TW. Pharmacokinetics, safety, and tolerability of oral semaglutide in subjects with hepatic impairment. J Clin Pharmacol. 2018;58:1314–23.CrossRef
12.
go back to reference Granhall C, Søndergaard FL, Thomsen M, Anderson TW. Pharmacokinetics, safety and tolerability of oral semaglutide in subjects with renal impairment. Clin Pharmacokinet. 2018;57:1571–80.CrossRef Granhall C, Søndergaard FL, Thomsen M, Anderson TW. Pharmacokinetics, safety and tolerability of oral semaglutide in subjects with renal impairment. Clin Pharmacokinet. 2018;57:1571–80.CrossRef
13.
go back to reference Aroda VR, Rosenstock J, Terauchi Y, PIONEER 1 Investigators, et al. 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;42:1724–32.CrossRef Aroda VR, Rosenstock J, Terauchi Y, PIONEER 1 Investigators, et al. 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;42:1724–32.CrossRef
14.
go back to reference Pratley R, Amod A, Hoff ST, PIONEER 4 investigators, et al. Oral semaglutide versus subcutaneous liraglutide and placebo in type 2 diabetes (PIONEER 4): a randomised, double-blind, phase 3a trial. Lancet. 2019;394:39–50.CrossRef Pratley R, Amod A, Hoff ST, PIONEER 4 investigators, et al. Oral semaglutide versus subcutaneous liraglutide and placebo in type 2 diabetes (PIONEER 4): a randomised, double-blind, phase 3a trial. Lancet. 2019;394:39–50.CrossRef
15.
go back to reference Zinman B, Aroda VR, Buse JB, PIONEER 8 Investigators, et al. 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;42:2262–71.CrossRef Zinman B, Aroda VR, Buse JB, PIONEER 8 Investigators, et al. 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;42:2262–71.CrossRef
16.
go back to reference Rosenstock J, Allison D, Birkenfeld AL, PIONEER 3 Investigators, et al. 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;321:1466–80.CrossRef Rosenstock J, Allison D, Birkenfeld AL, PIONEER 3 Investigators, et al. 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;321:1466–80.CrossRef
17.
go back to reference Rodbard HW, Rosenstock J, Canani LH, PIONEER 2 Investigators, et al. Oral semaglutide versus empagliflozin in patients with type 2 diabetes uncontrolled on metformin: the PIONEER 2 trial. Diabetes Care. 2019;42:2272–81.CrossRef Rodbard HW, Rosenstock J, Canani LH, PIONEER 2 Investigators, et al. Oral semaglutide versus empagliflozin in patients with type 2 diabetes uncontrolled on metformin: the PIONEER 2 trial. Diabetes Care. 2019;42:2272–81.CrossRef
18.
go back to reference Pieber TR, Bode B, Mertens A, PIONEER 7 investigators, et al. Efficacy and safety of oral semaglutide with flexible dose adjustment versus sitagliptin in type 2 diabetes (PIONEER 7): a multicentre, open-label, randomised, phase 3a trial. Lancet Diabetes Endocrinol. 2019;7:528–39.CrossRef Pieber TR, Bode B, Mertens A, PIONEER 7 investigators, et al. Efficacy and safety of oral semaglutide with flexible dose adjustment versus sitagliptin in type 2 diabetes (PIONEER 7): a multicentre, open-label, randomised, phase 3a trial. Lancet Diabetes Endocrinol. 2019;7:528–39.CrossRef
19.
go back to reference Mosenzon O, Blicher TM, Rosenlund S, PIONEER 5 Investigators, et al. 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;7:515–27.CrossRef Mosenzon O, Blicher TM, Rosenlund S, PIONEER 5 Investigators, et al. 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;7:515–27.CrossRef
20.
go back to reference Yamada Y, Katagiri H, Hamamoto Y, PIONEER 9 investigators, et al. Dose-response, efficacy, and safety of oral semaglutide monotherapy in Japanese patients with type 2 diabetes (PIONEER 9): a 52-week, phase 2/3a, randomised, controlled trial. Lancet Diabetes Endocrinol. 2020;8:377–91.CrossRef Yamada Y, Katagiri H, Hamamoto Y, PIONEER 9 investigators, et al. Dose-response, efficacy, and safety of oral semaglutide monotherapy in Japanese patients with type 2 diabetes (PIONEER 9): a 52-week, phase 2/3a, randomised, controlled trial. Lancet Diabetes Endocrinol. 2020;8:377–91.CrossRef
21.
go back to reference Yabe D, Nakamura J, Kaneto H, PIONEER 10 Investigators, et al. Safety and efficacy of oral semaglutide versus dulaglutide in Japanese patients with type 2 diabetes (PIONEER 10): an open-label, randomised, active-controlled, phase 3a trial. Lancet Diabetes Endocrinol. 2020;8:392–406.CrossRef Yabe D, Nakamura J, Kaneto H, PIONEER 10 Investigators, et al. Safety and efficacy of oral semaglutide versus dulaglutide in Japanese patients with type 2 diabetes (PIONEER 10): an open-label, randomised, active-controlled, phase 3a trial. Lancet Diabetes Endocrinol. 2020;8:392–406.CrossRef
22.
go back to reference Nuhoho S, Gupta J, Hansen BB, Fletcher-Louis M, Dang-Tan T, Paine A. Orally administered semaglutide versus GLP-1 RAs in patients with type 2 diabetes previously receiving 1–2 oral antidiabetics: systematic review and network meta-analysis. Diabetes Ther. 2019;10:2183–99.CrossRef Nuhoho S, Gupta J, Hansen BB, Fletcher-Louis M, Dang-Tan T, Paine A. Orally administered semaglutide versus GLP-1 RAs in patients with type 2 diabetes previously receiving 1–2 oral antidiabetics: systematic review and network meta-analysis. Diabetes Ther. 2019;10:2183–99.CrossRef
23.
go back to reference Husain M, Birkenfeld AL, Donsmark M, PIONEER 6 Investigators, et al. Oral semaglutide and cardiovascular outcomes in patients with type 2 diabetes. N Engl J Med. 2019;381:841–51.CrossRef Husain M, Birkenfeld AL, Donsmark M, PIONEER 6 Investigators, et al. Oral semaglutide and cardiovascular outcomes in patients with type 2 diabetes. N Engl J Med. 2019;381:841–51.CrossRef
24.
go back to reference 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;22:442–51.CrossRef 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;22:442–51.CrossRef
25.
go back to reference Alfayez OM, Almohammed OA, Alkhezi OS, Almutairi AR, Al Yami MS. Indirect comparison of glucagon like peptide-1 receptor agonists regarding cardiovascular safety and mortality in patients with type 2 diabetes mellitus: network meta-analysis. Cardiovasc Diabetol. 2020;19:96.CrossRef Alfayez OM, Almohammed OA, Alkhezi OS, Almutairi AR, Al Yami MS. Indirect comparison of glucagon like peptide-1 receptor agonists regarding cardiovascular safety and mortality in patients with type 2 diabetes mellitus: network meta-analysis. Cardiovasc Diabetol. 2020;19:96.CrossRef
26.
go back to reference Hansen BB, Nuhoho S, Ali SN, et al. Oral semaglutide versus injectable glucagon-like peptide-1 receptor agonists: a cost of control analysis. J Med Econ. 2020;23:650–8.CrossRef Hansen BB, Nuhoho S, Ali SN, et al. Oral semaglutide versus injectable glucagon-like peptide-1 receptor agonists: a cost of control analysis. J Med Econ. 2020;23:650–8.CrossRef
27.
go back to reference Hunt B, Hansen BB, Ericsson Å, et al. Evaluation of the cost per patient achieving treatment targets with oral semaglutide: a short-term cost-effectiveness analysis in the United States. Adv Ther. 2019;36:3483–93.CrossRef Hunt B, Hansen BB, Ericsson Å, et al. Evaluation of the cost per patient achieving treatment targets with oral semaglutide: a short-term cost-effectiveness analysis in the United States. Adv Ther. 2019;36:3483–93.CrossRef
28.
go back to reference Bain SC, Hansen BB, Malkin SJP, et al. Oral semaglutide versus empagliflozin, sitagliptin and liraglutide in the UK: long-term cost-effectiveness analyses based on the PIONEER clinical trial programme. Diabetes Ther. 2020;11:259–77.CrossRef Bain SC, Hansen BB, Malkin SJP, et al. Oral semaglutide versus empagliflozin, sitagliptin and liraglutide in the UK: long-term cost-effectiveness analyses based on the PIONEER clinical trial programme. Diabetes Ther. 2020;11:259–77.CrossRef
Metadata
Title
Oral Semaglutide, A New Option in the Management of Type 2 Diabetes Mellitus: A Narrative Review
Authors
Areti Sofogianni
Konstantinos Tziomalos
Publication date
01-10-2020
Publisher
Springer Healthcare
Published in
Advances in Therapy / Issue 10/2020
Print ISSN: 0741-238X
Electronic ISSN: 1865-8652
DOI
https://doi.org/10.1007/s12325-020-01478-9

Other articles of this Issue 10/2020

Advances in Therapy 10/2020 Go to the issue