Pharmaceutical composition comprising a glp-1 agonist, an insulin and methionine

Abstract

A liquid composition comprising a GLP-1 agonist or/and a pharmacologically tolerable salt thereof, an insulin or/and a pharmacologically tolerable salt thereof, and, optionally, at least one pharmaceutically acceptable excipient, wherein the composition comprises methionine, as add-on therapy with metformin where appropriate.

1 . An aqueous solution for subcutaneous injection comprising:
 (a) 0.033 mg desPro 36 exendin-4(1-39)-Lys 6 -NH 2 ,   (b) 3.64 mg Gly(A21)-Arg(B31)-Arg(B32) human insulin,   (c) 30 μg zinc,   (d) 2.7 mg m-cresol,   (e) 3 mg L-methionine,   (f) 20 mg glycerol, and   (g) water for injection, to a volume of 1 mL.   
     
     
         2 . The composition of  claim 1 , further comprising hydrochloric acid and sodium hydroxide as needed achieve a pH of about 4.5. 
     
     
         3 . The composition of  claim 1 , wherein the amount of water is at least 10% by weight. 
     
     
         4 . A prefilled syringe for subcutaneous injection comprising an aqueous solution comprising per 1 mL volume of the solution:
 (a) about 0.033 mg to about 0.1 mg desPro 36 exendin-4(1-39)-Lys 6 -NH 2  or a pharmacologically tolerable salt;   (b) about 3.64 mg insulin glargine or a pharmacologically tolerable salt thereof;   (c) about 3 mg methionine;   (d) about 2.7 mg m-cresol;   (e) about 20 mg 85% glycerol;   (f) about 0.06 mg zinc chloride; and   (g) water for injection, to a volume of 1 mL.   
     
     
         5 . The composition of  claim 4 , further comprising hydrochloric acid and sodium hydroxide as needed achieve a pH of about 4.5.