Clinical Pharmacokinetics of Semaglutide: A Systematic Review

References

• Ginsberg HN, MacCallum PR. The obesity, metabolic syndrome, and type 2 diabetes mellitus pandemic: part I. Increased cardiovascular disease risk and the importance of atherogenic dyslipidemia in persons with the metabolic syndrome and type 2 diabetes mellitus. J Cardiometab Syndr. 2009;4:113–119. doi:10.1111/j.1559-4572.2008.00044.x
   PubMedGoogle Scholar
• Tilinca MC, Tiuca RA, Niculas C, et al. Future perspectives in diabesity treatment: semaglutide, a glucagon‑like peptide 1 receptor agonist (Review). Exp Ther Med. 2021;22. doi:10.3892/etm.2021.10601
   PubMed Web of Science ®Google Scholar
• International Diabetes Federation (IDF). IDF diabetes atlas 10th edition. Available from: http://www.diabetesatlas.org/. Accessed June 19, 2024.
   Google Scholar
• Sun H, Saeedi P, Karuranga S, et al. IDF diabetes atlas: global, regional and country-level diabetes prevalence estimates for 2021 and projections for 2045. Diabet Res Clin Pract. 2022;183:109119. doi:10.1016/j.diabres.2021.109119
   PubMed Web of Science ®Google Scholar
• Hasanzad M, Sarhangi N. A narrative review of current trends in liraglutide: insights into the unmet needs in management of type 2 diabetes and obesity. J Diabetes Metab Disord. 2020;19:1863–1872. doi:10.1007/s40200-020-00619-9
   PubMed Web of Science ®Google Scholar
• Yang YY, Qi JJ, Jiang SY, et al. Esculin ameliorates obesity-induced insulin resistance by improving adipose tissue remodeling and activating the IRS1/PI3K/AKT/GLUT4 pathway. J Ethnopharmacol. 2024;319:117251. doi:10.1016/j.jep.2023.117251
   PubMed Web of Science ®Google Scholar
• Li X, Shi S, Jing D, et al. Signal transduction mechanism of exosomes in diabetic complications (Review). Exp Ther Med. 2022;23:155. doi:10.3892/etm.2021.11078
   PubMed Web of Science ®Google Scholar
• Gadde KM, Martin CK, Berthoud HR, et al. Obesity: pathophysiology and management. J Am Coll Cardiol. 2018;71:69–84. doi:10.1016/j.jacc.2017.11.011
   PubMed Web of Science ®Google Scholar
• World health organization obesity and overweight: world health organization global strategy on diet, physical activity and health fact sheet; 2003. Available from: http://www.who.int. Accessed September 16, 2005.
   Google Scholar
• Adlyxin (lixisenatide) [prescribing information]. Bridgewater: Sanofi-Aventis US LLC; 2016.
   Google Scholar
• Bydureon (exenatide) [prescribing information]. Wilmington: AstraZeneca Pharmaceuticals LP; 2017.
   Google Scholar
• Byetta (exenatide) [prescribing information]. Wilmington: AstraZeneca Pharmaceuticals; 2015.
   Google Scholar
• Tanzeum (albiglutide) [prescribing information]. Wilmington: GlaxoSmithKline; 2017.
   Google Scholar
• Victoza (liraglutide) [prescribing information]. Bagsvaerd: Novo Nordisk; 2017.
   Google Scholar
• Trulicity (dulaglutide) [prescribing information]. Indianapolis: Eli Lily and Company; 2017.
   Google Scholar
• Ladenheim EE. Liraglutide and obesity: a review of the data so far. Drug Des Devel Ther. 2015;9:1867–1875. doi:10.2147/dddt.s58459
   PubMed Web of Science ®Google Scholar
• Meier JJ. GLP-1 receptor agonists for individualized treatment of type 2 diabetes mellitus. Nat Rev Endocrinol. 2012;8:728–742. doi:10.1038/nrendo.2012.140
   PubMed Web of Science ®Google Scholar
• Romera I, Cebrián-Cuenca A, Álvarez-Guisasola F, et al. A review of practical issues on the use of glucagon-like peptide-1 receptor agonists for the management of type 2 diabetes. Diabetes Ther. 2019;10:5–19. doi:10.1007/s13300-018-0535-9
   PubMed Web of Science ®Google Scholar
• Isaacs D, Prasad-Reddy L, Srivastava SB. Role of glucagon-like peptide 1 receptor agonists in management of obesity. Am J Health Syst Pharm. 2016;73:1493–1507. doi:10.2146/ajhp150990
   PubMed Web of Science ®Google Scholar
• Lau J, Bloch P, Schäffer L, et al. Discovery of the once-weekly glucagon-like peptide-1 (GLP-1) analogue semaglutide. J Med Chem. 2015;58:7370–7380. doi:10.1021/acs.jmedchem.5b00726
   PubMed Web of Science ®Google Scholar
• Sorli C, Harashima SI, Tsoukas 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 3a trial. Lancet Diabetes Endocrinol. 2017;5:251–260. doi:10.1016/s2213-8587(17)30013-x
   PubMed Web of Science ®Google Scholar
• Ahrén 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;5:341–354. doi:10.1016/s2213-8587(17)30092-x
   PubMed Web of Science ®Google Scholar
• 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 Clin Trial. 2018;41:258–266. doi:10.2337/dc17-0417
   Google Scholar
• 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;5:355–366. doi:10.1016/s2213-8587(17)30085-2
   PubMed Web of Science ®Google Scholar
• 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;103:2291–2301. doi:10.1210/jc.2018-00070
   PubMed Web of Science ®Google Scholar
• 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;6:275–286. doi:10.1016/s2213-8587(18)30024-x
   PubMed Web of Science ®Google Scholar
• Aroda VR, Ahmann A, Cariou B, et al. Comparative efficacy, safety, and cardiovascular outcomes with once-weekly subcutaneous semaglutide in the treatment of type 2 diabetes: insights from the SUSTAIN 1-7 trials. Diabetes Metab. 2019;45:409–418. doi:10.1016/j.diabet.2018.12.001
   PubMed Web of Science ®Google Scholar
• Jensen L, Helleberg H, Roffel A, et al. 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
   PubMed Web of Science ®Google Scholar
• Jensen L, Kupcova V, Arold G, et al. Pharmacokinetics and tolerability of semaglutide in people with hepatic impairment. Diabetes Obesity Metab. 2018;20:998–1005. doi:10.1111/dom.13186
   PubMed Web of Science ®Google Scholar
• Beglinger C, Poller B, Arbit E, et al. Pharmacokinetics and pharmacodynamic effects of oral GLP-1 and PYY3-36: a proof-of-concept study in healthy subjects. Clin Pharmacol Ther. 2008;84:468–474. doi:10.1038/clpt.2008.35
   PubMed Web of Science ®Google Scholar
• Andersen A, Knop FK, Vilsbøll T. A pharmacological and clinical overview of oral semaglutide for the treatment of type 2 diabetes. Drugs. 2021;81:1003–1030. doi:10.1007/s40265-021-01499-w
   PubMed Web of Science ®Google Scholar
• Page MJ, McKenzie JE, Bossuyt PM, et al. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. BMJ. 2021;372:n71. doi:10.1136/bmj.n71
   PubMed Web of Science ®Google Scholar
• Ikushima I, Jensen L, Flint A, et al. A randomized trial investigating the pharmacokinetics, pharmacodynamics, and safety of subcutaneous semaglutide once-weekly in healthy male Japanese and caucasian subjects. Adv Ther. 2018;35:531–544. doi:10.1007/s12325-018-0677-1
   PubMed Web of Science ®Google Scholar
• Shi A, Xie P, Nielsen LL, et al. Pharmacokinetics, safety and tolerability of once-weekly subcutaneous semaglutide in healthy Chinese subjects: a double-blind, phase 1, randomized controlled trial. Adv Ther. 2021;38:550–561. doi:10.1007/s12325-020-01548-y
   PubMed Web of Science ®Google Scholar
• Kapitza C, Nosek L, Jensen L, et al. Semaglutide, a once-weekly human GLP-1 analog, does not reduce the bioavailability of the combined oral contraceptive, ethinylestradiol/levonorgestrel. ACS Chem Biol. 2015;55:497–504. doi:10.1002/jcph.443
   Google Scholar
• Blundell J, Finlayson G, Axelsen M, et al. 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;19:1242–1251. doi:10.1111/dom.12932
   PubMed Web of Science ®Google Scholar
• Marbury TC, Flint A, Jacobsen JB, et al. Pharmacokinetics and tolerability of a single dose of semaglutide, a human glucagon-like peptide-1 analog, in subjects with and without renal impairment. Clin Pharmacokinet. 2017;56:1381–1390. doi:10.1007/s40262-017-0528-2
   PubMed Web of Science ®Google Scholar
• Enebo LB, Berthelsen KK, Kankam M, et al. Safety, tolerability, pharmacokinetics, and pharmacodynamics of concomitant administration of multiple doses of cagrilintide with semaglutide 2·4 mg for weight management: a randomised, controlled, phase 1b trial. Lancet. 2021;397:1736–1748. doi:10.1016/s0140-6736(21)00845-x
   PubMed Web of Science ®Google Scholar
• Granhall C, Donsmark M, Blicher TM, et al. Safety and pharmacokinetics of single and multiple ascending doses of the novel oral human GLP-1 analogue, oral semaglutide, in healthy subjects and subjects with type 2 diabetes. Clin Pharmacokinet. 2019;58:781–791. doi:10.1007/s40262-018-0728-4
   PubMed Web of Science ®Google Scholar
• Bækdal TA, Donsmark M, Hartoft-Nielsen ML, et al. Relationship between oral semaglutide tablet erosion and pharmacokinetics: a pharmacoscintigraphic study. Clin Pharmacol Drug Dev. 2021;10:453–462. doi:10.1002/cpdd.938
   PubMed Web of Science ®Google Scholar
• Bækdal TA, Breitschaft A, Donsmark M, et al. Effect of various dosing conditions on the pharmacokinetics of oral semaglutide, a human glucagon-like peptide-1 analogue in a tablet formulation. Diabetes Ther. 2021;12:1915–1927. doi:10.1007/s13300-021-01078-y
   PubMed Web of Science ®Google Scholar
• Hauge C, Breitschaft A, Hartoft-Nielsen ML, et al. Effect of oral semaglutide on the pharmacokinetics of thyroxine after dosing of levothyroxine and the influence of co-administered tablets on the pharmacokinetics of oral semaglutide in healthy subjects: an open-label, one-sequence crossover, single-center, multiple-dose, two-part trial. Clin Pharmacokinet. 2021;17:1139–1148. doi:10.1080/17425255.2021.1955856
   Google Scholar
• van Hout M, Forte P, Jensen TB, et al. Effect of various dosing schedules on the pharmacokinetics of oral semaglutide: a randomised trial in healthy subjects. Clin Pharmacokinet. 2023;62:635–644. doi:10.1007/s40262-023-01223-9
   PubMed Web of Science ®Google Scholar
• Bækdal TA, Thomsen M, Kupčová V, et al. Pharmacokinetics, safety, and tolerability of oral semaglutide in subjects with hepatic impairment. J Clin Pharmacol. 2018;58:1314–1323. doi:10.1002/jcph.1131
   PubMed Web of Science ®Google Scholar
• Granhall C, Søndergaard FL, Thomsen M, et al. Pharmacokinetics, safety and tolerability of oral semaglutide in subjects with renal impairment. Clin Pharmacokinet. 2018;57:1571–1580. doi:10.1007/s40262-018-0649-2
   PubMed Web of Science ®Google Scholar
• Meier JJ, Granhall C, Hoevelmann U, et al. Effect of upper gastrointestinal disease on the pharmacokinetics of oral semaglutide in subjects with type 2 diabetes. Diabetes Obesity Metab. 2022;24:684–692. doi:10.1111/dom.14632
   PubMed Web of Science ®Google Scholar
• Bækdal TA, Breitschaft A, Navarria A, et al. A randomized study investigating the effect of omeprazole on the pharmacokinetics of oral semaglutide. Expert Opin Drug Metab Toxicol. 2018;14:869–877. doi:10.1080/17425255.2018.1488965
   PubMed Web of Science ®Google Scholar
• Al-Dirini RM, Thewlis D, Paul G. A comprehensive literature review of the pelvis and the lower extremity FE human models under quasi-static conditions. Work. 2012;41(Suppl 1):4218–4229. doi:10.3233/wor-2012-1039-4218
   PubMedGoogle Scholar
• CASP(Critical Skills Appraisal Programme)[EB/OL]; 2012. Available from: https://casp-uk.net/casp-tools-checklists. Accessed June 19, 2024.
   Google Scholar
• Overgaard RV, Navarria A, Ingwersen SH, et al. Clinical pharmacokinetics of oral semaglutide: analyses of data from clinical pharmacology trials. Clin Pharmacokinet. 2021;60:1335–1348. doi:10.1007/s40262-021-01025-x
   PubMed Web of Science ®Google Scholar
• Hellriegel ET, Bjornsson TD, Hauck WW. Interpatient variability in bioavailability is related to the extent of absorption: implications for bioavailability and bioequivalence studies. Clin Pharmacol Ther. 1996;60:601–607. doi:10.1016/s0009-9236(96)90208-8
   PubMed Web of Science ®Google Scholar
• Davies M, Pieber TR, Hartoft-Nielsen ML, et al. Effect of oral semaglutide compared with placebo and subcutaneous semaglutide on glycemic control in patients with type 2 diabetes: a randomized clinical trial. JAMA. 2017;318:1460–1470. doi:10.1001/jama.2017.14752
   PubMed Web of Science ®Google Scholar
• Overgaard RV, Delff PH, Petri KCC, et al. Population pharmacokinetics of semaglutide for type 2 diabetes. Diabetes Ther. 2019;10:649–662. doi:10.1007/s13300-019-0581-y
   PubMed Web of Science ®Google Scholar
• Carlsson Petri KC, Ingwersen SH, Flint A, et al. Semaglutide s.c. Once-weekly in type 2 diabetes: a population pharmacokinetic analysis. Diabetes Therapy. 2018;9:1533–1547. doi:10.1007/s13300-018-0458-5
   PubMed Web of Science ®Google Scholar
• Hausner H, Derving Karsbøl J, Holst AG, et al. Effect of semaglutide on the pharmacokinetics of metformin, warfarin, atorvastatin and digoxin in healthy subjects. Clin Pharmacokinet. 2017;56:1391–1401. doi:10.1007/s40262-017-0532-6
   PubMed Web of Science ®Google Scholar
• Langeskov EK. Population pharmacokinetic of paracetamol and atorvastatin with co-administration of semaglutide. Int J Mol Sci. 2022;10:e00962. doi:10.1002/prp2.962
   Google Scholar
• Bækdal TA, Borregaard J, Hansen CW, et al. Effect of oral semaglutide on the pharmacokinetics of lisinopril, warfarin, digoxin, and metformin in healthy subjects. Clin Pharmacokinet. 2019;58:1193–1203. doi:10.1007/s40262-019-00756-2
   PubMed Web of Science ®Google Scholar
• Borregaard J, Bækdal TA, Golor G, et al. A study of drug-drug interactions of oral semaglutide with lisinopril and warfarin. Diabetes. 2017;66:A321.
   Web of Science ®Google Scholar
• Jordy AB, Albayaty M, Breitschaft A, et al. Effect of oral semaglutide on the pharmacokinetics of levonorgestrel and ethinylestradiol in healthy postmenopausal women and furosemide and rosuvastatin in healthy subjects. Pharmaceutics. 2021;60:1171–1185. doi:10.1007/s40262-020-00976-x
   Google Scholar
• Jordy AB, Breitschaft A, Christiansen E, et al. Oral semaglutide does not affect the bioavailability of the combined oral contraceptive ethinylestradiol/levonorgestrel. Diabetes. 2018;67:A304.
   Web of Science ®Google Scholar
• Jordy AB, Breitschaft A, Christiansen E, et al. Oral semaglutide does not affect the bioavailability of the combined oral contraceptive, ethinylestradiol/levonorgestrel. Diabetologia. 2018;61:S346. doi:10.1007/s00125-018-4693-0
   Web of Science ®Google Scholar
• Thomsen M, Bækdal TA, Golor G, et al. A study of drug-drug interactions of oral semaglutide with metformin and digoxin. Diabetologia. 2017;60:S363. doi:10.1007/s00125-017-4350-z
   Web of Science ®Google Scholar
• Bækdal TA, Albayaty M, Manigandan E, et al. A trial to investigate the effect of oral semaglutide on the pharmacokinetics of furosemide and rosuvastatin in healthy subjects. Diabetologia. 2018;61:S346–S347. doi:10.1007/s00125-018-4693-0
   Web of Science ®Google Scholar
• Lewis AL, McEntee N, Holland J, et al. Development and approval of rybelsus (oral semaglutide): ushering in a new era in peptide delivery. Drug Deliv Transl Res. 2022;12:1–6. doi:10.1007/s13346-021-01000-w
   PubMed Web of Science ®Google Scholar
• Moriwaki N, Akahori M, Sugii H. Development of Rybelsus, the world’s first oral GLP-1 receptor agonist. Drug Deliv Sys. 2022;37:169–173. doi:10.2745/dds.37.169
   Google Scholar
• Nauck MA, Gallwitz B, Seufert J. Semaglutide- pharmacodynamic and pharmacokinetic characteristics of a new long-acting GLP-1-receptor agonist. Diabetol Stoffwechs. 2017;12:135–140. doi:10.1055/s-0043-104866
   Web of Science ®Google Scholar