Oral dosing of GLP-1 compounds
The present invention relates to improved uses of GLP-1 peptides in oral therapy.
1. A method for treating diabetes and/or obesity in a subject in need of such treatment, said method comprising:
orally administering to said subject a therapeutically effective amount of a solid oral dosage form composition comprising a glucagon-like peptide-1 (GLP-1) peptide and an enhancer,
wherein:
(a) the GLP-1 peptide is an acylated GLP-1 analogue having 3 amino acid substitutions or less relative to native GLP-1 (7-37) peptide, and has a plasma half-life in humans of at least 60 hours;
(b) the enhancer is a salt of N-(8-(2-hydroxybenzoyl)amino)caprylic acid; and
(c) said composition is administered such that the ratio between the plasma half-life in days in humans of said peptide and the dosing interval in days of said composition is more than 2:1.
2. The method of claim 1 , wherein said GLP-1 peptide is selected from the group consisting of N-epsilon26-[2-(2-{2-[2-(2-{2-[(S)-4-Carboxy-4-(17-carboxyheptadecanoylamino)butyryl-amino]ethoxy}ethoxy)acetylamino]ethoxy}ethoxy)acetyl][Aib8,Arg34]GLP-1-(7-37) (semaglutide), and
N ε37 {2-[2-(2-{2-[2-(2-{(S)-4-carboxy-4-[10-(4-carboxyphenoxy)decanoylamino]butyrylamino}ethoxy)ethoxy]acetylamino}ethoxy)ethoxy]acetyl}-[Aib 8 ,Arg 34 ,Lys 37 ]GLP-1(7-37)-OH.
3. The method of claim 2 , wherein said composition is administered every second day or more frequently.
4. The method of claim 3 , wherein said composition is administered once daily.
5. The method of claim 3 , wherein said composition is in the form of a tablet, capsule, sachet, or granules.
6. The method of claim 5 , wherein said composition is in the form of a tablet.
7. The method of claim 3 , wherein said GLP-1 peptide is semaglutide.
8. The method of claim 6 , wherein the enhancer is sodium N-(8-(2-hydroxybenzoyl)amino)caprylate (SNAC).
9. The method of claim 8 , wherein said composition comprises 2-40 mg semaglutide and 200-400 mg SNAC.
10. The method of claim 9 , wherein said composition is administered every second day or more frequently.
11. The method of claim 10 , wherein said composition is administered once daily.
12. The method of claim 9 , wherein said composition is in the form of a tablet, capsule, sachet, or granules.
13. The method of claim 12 , wherein said composition is in the form of a tablet.
14. A method for treating diabetes and/or obesity in a subject in need of such treatment, said method comprising:
orally administering to said subject a therapeutically effective amount of a solid oral dosage form composition comprising a glucagon-like peptide-1 (GLP-1) peptide and an enhancer,
wherein the GLP-1 peptide is:
(a) selected from the group consisting of N-epsilon26-[2-(2-{2-[2-(2-{2-[(S)-4-Carboxy-4-(17-carboxyheptadecanoylamino)butyryl-amino]ethoxy}ethoxy)acetylamino]ethoxy}ethoxy)acetyl][Aib8,Arg34]GLP-1-(7-37) (semaglutide) and N ε37 {2-[2-(2-{2-[2-(2-{(S)-4-carboxy-4-[10-(4-carboxyphenoxy)decanoylamino]butyrylamino}ethoxy)ethoxy]acetylamino}ethoxy)ethoxy]acetyl}-[Aib 8 ,Arg 34 ,Lys 37 ]GLP-1(7-37)-OH; and
(b) has a plasma half-life in humans of at least 60 hours;
wherein the enhancer is sodium N-(8-(2-hydroxybenzoyl)amino)caprylate (SNAC); and
wherein said composition is administered every second day or more frequently.
15. The method of claim 14 , wherein said composition comprises 2-40 mg semaglutide and 200-400 mg SNAC.
16. The method of claim 15 , wherein said composition is administered once daily.
17. The method of claim 15 , wherein said composition is in the form of a tablet, capsule, sachet, or granules.
18. The method of claim 17 , wherein said composition is in the form of a tablet.
19. The method of claim 8 , wherein said composition comprises 300 mg of SNAC.
20. The method of claim 15 , wherein said composition comprises 300 mg of SNAC.
21. A method for treating diabetes and/or obesity in a subject in need of such treatment, said method comprising:
orally administering to said subject a therapeutically effective amount of a solid oral dosage form composition comprising a glucagon-like peptide-1 (GLP-1) peptide and an enhancer,
wherein:
(a) the GLP-1 peptide is N-epsilon26-[2-(2-{2-[2-(2-{2-[(S)-4-Carboxy-4-(17-carboxyheptadecanoylamino)butyryl-amino]ethoxy}ethoxy)acetylamino]ethoxy}ethoxy)acetyl][Aib8,Arg34]GLP-1-(7-37) (semaglutide) and has a plasma half-life in humans of at least 60 hours;
(b) the enhancer is sodium N-(8-(2-hydroxybenzoyl)amino)caprylate (SNAC); and
(c) the composition is administered once daily.
22. The method of claim 21 , wherein said composition comprises 2-40 mg semaglutide and 200-400 mg SNAC.
23. The method of claim 22 , wherein said composition comprises 300 mg of SNAC.