Oral Semaglutide In The Management Of Type 2 Diabetes: A Report On The Evidence To Date

References

• Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type. 2 diabetes (UKPDS 33). UK Prospective Diabetes Study (UKPDS) Group. Lancet . 1998;352(9131):837–853.9742976
   PubMed Web of Science ®Google Scholar
• Holman RR , Paul SK , Bethel MA , Matthews DR , Neil HA . 10-year follow-up of intensive glucose control in type 2 diabetes. N Engl J Med . 2008;359(15):1577–1589. doi:10.1056/NEJMoa0806470 18784090
   PubMed Web of Science ®Google Scholar
• Nissen SE , Wolski K . Effect of rosiglitazone on the risk of myocardial infarction and death from cardiovascular causes. N Engl J Med . 2007;356(24):2457–2471. doi:10.1056/NEJMoa072761 17517853
   PubMed Web of Science ®Google Scholar
• Zinman B , Wanner C , Lachin JM , et al. Empagliflozin, Cardiovascular outcomes, and mortality in type 2 diabetes. N Engl J Med . 2015;373(22):2117–2128. doi:10.1056/NEJMoa1504720 26378978
   PubMed Web of Science ®Google Scholar
• Marso SP , Daniels GH , Brown-Frandsen K , et al. Liraglutide and cardiovascular outcomes in type 2 diabetes. N Engl J Med . 2016;375(4):311–322. doi:10.1056/NEJMoa1603827 27295427
   PubMed Web of Science ®Google Scholar
• Theodorakis MJ , Carlson O , Michopoulos S , et al. Human duodenal enteroendocrine cells: source of both incretin peptides, GLP-1 and GIP. Am J Physiol Endocrinol Metab . 2006;290(3):E550–559. doi:10.1152/ajpendo.00326.2004 16219666
   PubMed Web of Science ®Google Scholar
• Mojsov S , Weir GC , Habener JF . Insulinotropin: glucagon-like peptide I (7-37) co-encoded in the glucagon gene is a potent stimulator of insulin release in the perfused rat pancreas. J Clin Invest . 1987;79(2):616–619. doi:10.1172/JCI112855 3543057
   PubMed Web of Science ®Google Scholar
• Holst JJ . The physiology of glucagon-like peptide 1. Physiol Rev . 2007;87(4):1409–1439. doi:10.1152/physrev.00034.2006 17928588
   PubMed Web of Science ®Google Scholar
• Doyle ME , Egan JM . Mechanisms of action of glucagon-like peptide 1 in the pancreas. Pharmacol Ther . 2007;113(3):546–593. doi:10.1016/j.pharmthera.2006.11.007 17306374
   PubMed Web of Science ®Google Scholar
• Mentlein R . Dipeptidyl-peptidase IV (CD26)–role in the inactivation of regulatory peptides. Regul Pept . 1999;85(1):9–24. doi:10.1016/S0167-0115(99)00089-0 10588446
   PubMed Web of Science ®Google Scholar
• Green BD , Flatt PR , Bailey CJ . Dipeptidyl peptidase IV (DPP IV) inhibitors: a newly emerging drug class for the treatment of type 2 diabetes. Diabetes Vasc Dis Res . 2006;3(3):159–165. doi:10.3132/dvdr.2006.024
   PubMedGoogle Scholar
• Hunt JN , Smith JL , Jiang CL . Effect of meal volume and energy density on the gastric emptying of carbohydrates. Gastroenterology . 1985;89(6):1326–1330. doi:10.1016/0016-5085(85)90650-X 4054524
   PubMed Web of Science ®Google Scholar
• Horowitz M , Edelbroek MA , Wishart JM , Straathof JW . Relationship between oral glucose tolerance and gastric emptying in normal healthy subjects. Diabetologia . 1993;36(9):857–862. doi:10.1007/BF00400362 8405758
   PubMed Web of Science ®Google Scholar
• Vrang N , Larsen PJ . Preproglucagon derived peptides GLP-1, GLP-2 and oxyntomodulin in the CNS: role of peripherally secreted and centrally produced peptides. Prog Neurobiol . 2010;92(3):442–462. doi:10.1016/j.pneurobio.2010.07.003 20638440
   PubMed Web of Science ®Google Scholar
• Merchenthaler I , Lane M , Shughrue P . Distribution of pre-pro-glucagon and glucagon-like peptide-1 receptor messenger RNAs in the rat central nervous system. J Comp Neurol . 1999;403(2):261–280. doi:10.1002/(ISSN)1096-9861 9886047
   PubMed Web of Science ®Google Scholar
• During MJ , Cao L , Zuzga DS , et al. Glucagon-like peptide-1 receptor is involved in learning and neuroprotection. Nat Med . 2003;9(9):1173–1179. doi:10.1038/nm919 12925848
   PubMed Web of Science ®Google Scholar
• Hayes MR , Skibicka KP , Grill HJ . Caudal brainstem processing is sufficient for behavioral, sympathetic, and parasympathetic responses driven by peripheral and hindbrain glucagon-like-peptide-1 receptor stimulation. Endocrinology . 2008;149(8):4059–4068. doi:10.1210/en.2007-1743 18420740
   PubMed Web of Science ®Google Scholar
• Knauf C , Cani PD , Perrin C , et al. Brain glucagon-like peptide-1 increases insulin secretion and muscle insulin resistance to favor hepatic glycogen storage. J Clin Invest . 2005;115(12):3554–3563. doi:10.1172/JCI25764 16322793
   PubMed Web of Science ®Google Scholar
• Turton MD , O’Shea D , Gunn I , et al. A role for glucagon-like peptide-1 in the central regulation of feeding. Nature . 1996;379(6560):69–72. doi:10.1038/379069a0 8538742
   PubMed Web of Science ®Google Scholar
• Tsai TH , Lee CH , Cheng CI , et al. Liraglutide inhibits endothelial-to-mesenchymal transition and attenuates neointima formation after endovascular injury in streptozotocin-induced diabetic mice. Cells . 2019;8(6). doi:10.3390/cells8020137.
   Web of Science ®Google Scholar
• Breton-Romero R , Weisbrod RM , Feng B , et al. Liraglutide treatment reduces endothelial endoplasmic reticulum stress and insulin resistance in patients with diabetes mellitus. J Am Heart Assoc . 2018;7(18):e009379. doi:10.1161/JAHA.118.009379 30371206
   PubMed Web of Science ®Google Scholar
• Egholm C , Khammy MM , Dalsgaard T , et al. GLP-1 inhibits VEGFA-mediated signaling in isolated human endothelial cells and VEGFA-induced dilation of rat mesenteric arteries. Am J Physiol Heart Circ Physiol . 2016;311(5):H1214–H1224. doi:10.1152/ajpheart.00316.2016 27638877
   PubMed Web of Science ®Google Scholar
• Htike ZZ , Zaccardi F , Papamargaritis D , Webb DR , Khunti K , Davies MJ . Efficacy and safety of glucagon-like peptide-1 receptor agonists in type 2 diabetes: a systematic review and mixed-treatment comparison analysis. Diabetes Obes Metab . 2017;19(4):524–536. doi:10.1111/dom.12849 27981757
   PubMed Web of Science ®Google Scholar
• Holman RR , Bethel MA , Mentz RJ , et al. Effects of once-weekly exenatide on cardiovascular outcomes in type 2 diabetes. N Engl J Med . 2017;377(13):1228–1239. doi:10.1056/NEJMoa1612917 28910237
   PubMed Web of Science ®Google Scholar
• Pfeffer MA , Claggett B , Diaz R , et al. Lixisenatide in patients with type 2 diabetes and acute coronary syndrome. N Engl J Med . 2015;373(23):2247–2257. doi:10.1056/NEJMoa1509225 26630143
   PubMed Web of Science ®Google Scholar
• Gerstein HC , Colhoun HM , Dagenais GR , et al. Dulaglutide and cardiovascular outcomes in type 2 diabetes (REWIND): a double-blind, randomised placebo-controlled trial. Lancet . 2019;394(10193):121–130.31189511
   PubMed Web of Science ®Google Scholar
• Marso SP , Bain SC , Consoli A , et al. Semaglutide and cardiovascular outcomes in patients with type 2 diabetes. N Engl J Med . 2016;375(19):1834–1844. doi:10.1056/NEJMoa1607141 27633186
   PubMed Web of Science ®Google Scholar
• Andersen A , Lund A , Knop FK , Vilsboll T . Glucagon-like peptide 1 in health and disease. Nat Rev Endocrinol . 2018;14(7):390–403. doi:10.1038/s41574-018-0016-2 29728598
   PubMed Web of Science ®Google Scholar
• 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;11:2. doi:10.3390/pharmaceutics11020078
   Web of Science ®Google Scholar
• Mahato RI , Narang AS , Thoma L , Miller DD . Emerging trends in oral delivery of peptide and protein drugs. Crit Rev Ther Drug Carrier Syst . 2003;20(2–3):153–214. doi:10.1615/CritRevTherDrugCarrierSyst.v20.i23 14584523
   PubMed Web of Science ®Google Scholar
• Karsdal MA , Henriksen K , Bay-Jensen AC , et al. Lessons learned from the development of oral calcitonin: the first tablet formulation of a protein in phase III clinical trials. J Clin Pharmacol . 2011;51(4):460–471. doi:10.1177/0091270010372625 20660294
   PubMed Web of Science ®Google Scholar
• Karsdal MA , Byrjalsen I , Henriksen K , Riis BJ , Christiansen C . Investigations of inter- and intraindividual relationships between exposure to oral salmon calcitonin and a surrogate marker of pharmacodynamic efficacy. Eur J Clin Pharmacol . 2010;66(1):29–37. doi:10.1007/s00228-009-0735-3 19813008
   PubMed Web of Science ®Google Scholar
• Hammerle SP , Mindeholm L , Launonen A , et al. The single dose pharmacokinetic profile of a novel oral human parathyroid hormone formulation in healthy postmenopausal women. Bone . 2012;50(4):965–973. doi:10.1016/j.bone.2012.01.009 22289659
   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(4):468–474. doi:10.1038/clpt.2008.35 19238651
   PubMed Web of Science ®Google Scholar
• Castelli MC , Wong DF , Friedman K , Riley MG . Pharmacokinetics of oral cyanocobalamin formulated with sodium N-[8-(2-hydroxybenzoyl)amino]caprylate (SNAC): an open-label, randomized, single-dose, parallel-group study in healthy male subjects. Clin Ther . 2011;33(7):934–945. doi:10.1016/j.clinthera.2011.05.088 21722960
   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(6):781–791. doi:10.1007/s40262-018-0728-4 30565096
   PubMed Web of Science ®Google Scholar
• Buckley ST , Baekdal TA , Vegge A , et al. Transcellular stomach absorption of a derivatized glucagon-like peptide-1 receptor agonist. Sci Transl Med . 2018;10(467). doi:10.1126/scitranslmed.aar7047.
   PubMed Web of Science ®Google Scholar
• Aroda VR , Rosenstock J , Terauchi Y , et al. PIONEER 1: randomized clinical trial comparing the efficacy and safety of oral semaglutide monotherapy with placebo in patients with type 2 diabetes. Diabetes Care . 2019. doi:10.2337/dc19-0749
   Web of Science ®Google Scholar
• Pratley R , Amod A , Hoff ST , 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(10192):39–50. doi:10.1016/S0140-6736(19)31271-1 31186120
   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(4):251–260. doi:10.1016/S2213-8587(17)30013-X 28110911
   PubMed Web of Science ®Google Scholar
• Wiviott SD , Raz I , Bonaca MP , et al. Dapagliflozin and cardiovascular outcomes in type 2 diabetes. N Engl J Med . 2019;380(4):347–357. doi:10.1056/NEJMoa1812389 30415602
   PubMed Web of Science ®Google Scholar
• Neal B , Perkovic V , Mahaffey KW , et al. Canagliflozin and cardiovascular and renal events in type 2 diabetes. N Engl J Med . 2017;377(7):644–657. doi:10.1056/NEJMoa1611925 28605608
   PubMed Web of Science ®Google Scholar
• MONTANYA E , ROSENSTOCK J , LH CANANI , et al. 54-OR: oral Semaglutide vs. Empagliflozin added on to metformin monotherapy in uncontrolled type 2 diabetes: PIONEER 2. Diabetes . 2019;68(Supplement 1):54–OR. doi:10.2337/db19-54-OR
   Web of Science ®Google Scholar
• Deacon CF . A review of dipeptidyl peptidase-4 inhibitors. Hot topics from randomized controlled trials. Diabetes Obes Metab . 2018;20(Suppl 1):34–46. doi:10.1111/dom.2018.20.issue-S1
   Google Scholar
• Rosenstock J , Allison D , Birkenfeld AL , 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. doi:10.1001/jama.2019.2942
   Web of Science ®Google Scholar
• Pieber TR , Bode B , Mertens A , 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(7):528–539. doi:10.1016/S2213-8587(19)30194-9 31189520
   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 28323117
   PubMed Web of Science ®Google Scholar
• Granhall C , Sondergaard FL , Thomsen M , Anderson TW , Pharmacokinetics S . Tolerability of oral semaglutide in subjects with renal impairment. Clin Pharmacokinet . 2018;57(12):1571–1580. doi:10.1007/s40262-018-0649-2 29623579
   PubMed Web of Science ®Google Scholar
• Mosenzon O , Blicher TM , Rosenlund S , 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(7):515–527. doi:10.1016/S2213-8587(19)30192-5 31189517
   PubMed Web of Science ®Google Scholar
• Gier B , Matveyenko AV , Kirakossian D , et al. 1 receptor activation by exendin-4 induces expansion of pancreatic duct glands in rats and accelerates formation of dysplastic lesions and chronic pancreatitis in the Kras(G12D) mouse model. Diabetes . 2012;61(5):1250–1262. doi:10.2337/db11-1109 22266668
   PubMed Web of Science ®Google Scholar
• He L , Zhang S , Zhang X , Liu R , Guan H , Zhang H . Effects of insulin analogs and glucagon-like peptide-1 receptor agonists on proliferation and cellular energy metabolism in papillary thyroid cancer. Onco Targets Ther . 2017;10:5621–5631. doi:10.2147/OTT.S150701 29200876
   PubMed Web of Science ®Google Scholar
• Tang H , Li G , Zhao Y , et al. Comparisons of diabetic retinopathy events associated with glucose-lowering drugs in patients with type 2 diabetes mellitus: a network meta-analysis. Diabetes Obes Metab . 2018;20(5):1262–1279. doi:10.1111/dom.13232 29369494
   PubMed Web of Science ®Google Scholar
• Davies MJ , D’Alessio DA , Fradkin J , et al. 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 . 2018;61(12):2461–2498.30288571
   PubMed Web of Science ®Google Scholar
• Lau J , Bloch P , Schaffer L , et al. Discovery of the once-weekly glucagon-like peptide-1 (GLP-1) analogue semaglutide. J Med Chem . 2015;58(18):7370–7380. doi:10.1021/acs.jmedchem.5b00726 26308095
   PubMed Web of Science ®Google Scholar
• Knudsen LB , Lau J . The discovery and development of liraglutide and semaglutide. Front Endocrinol (Lausanne) . 2019;10:155.31031702
   PubMed Web of Science ®Google Scholar
• Larsen J , Hylleberg B , Ng K , Damsbo P . Glucagon-like peptide-1 infusion must be maintained for 24 h/day to obtain acceptable glycemia in type 2 diabetic patients who are poorly controlled on sulphonylurea treatment. Diabetes Care . 2001;24(8):1416–1421. doi:10.2337/diacare.24.8.1416 11473079
   PubMed Web of Science ®Google Scholar
• Husain M , Birkenfeld AL , Donsmark M , et al. Oral semaglutide and cardiovascular outcomes in patients with type 2 diabetes. N Engl J Med . 2019. doi:10.1056/NEJMoa1901118
   Web of Science ®Google Scholar
• Baekdal TA , Thomsen M , Kupcova V , Hansen CW , Anderson TW , Pharmacokinetics S . Tolerability of oral semaglutide in subjects with hepatic impairment. J Clin Pharmacol . 2018;58(10):1314–1323. doi:10.1002/jcph.1131 29693715
   PubMed Web of Science ®Google Scholar
• Liu Y , Tian Q , Yang J , Wang H , Hong T . No pancreatic safety concern following glucagon-like peptide-1 receptor agonist therapies: a pooled analysis of cardiovascular outcome trials. Diabetes Metab Res Rev . 2018;34(8):e3061. doi:10.1002/dmrr.v34.8 30109766
   PubMed Web of Science ®Google Scholar