Dosing regimen

A long acting insulin analogue for use in reducing the risk of hypoglycaemia in a patient suffering from diabetes and requiring amounts of delivered insulin of greater than 80 U/administration, wherein the long acting insulin analogue is administered to said patient in an amount of greater than 80 U/administration and in the form of a pharmaceutical composition comprising said insulin at a concentration of greater than 100 U/ml,

• and wherein the long acting insulin analogue is a naturally occurring insulin or an insulin analogue having a side chain attached either to the α-amino group of the N-terminal amino acid residue of the B chain or to the ε-amino group of a Lys residue present in the B chain of the parent insulin, the side chain being of the general formula (I):
• —W—X—Y—Z
• wherein W is:
• an α-amino acid residue having a carboxylic acid group in the side chain which residue forms, with one of its carboxylic acid groups, an amide group together with the α-amino group of the N-terminal amino acid residue of the B chain or together with the ε-amino group of a Lys residue present in the B chain of the parent insulin;
• a chain composed of two, three or four α-amino acid residues linked together via amide bonds, which chain—via an amide bond—is linked to the α-amino group of the N-terminal amino acid residue of the B chain or to the ε-amino group of a Lys residue present in the B chain of the parent insulin, the amino acid residues of W being selected from the group of amino acid residues having a neutral side chain and amino acid residues having a carboxylic acid group in the side chain so that W has at least one amino acid residue which has a carboxylic acid group in the side chain;
• or
• a covalent bond from X to the α-amino group of the N-terminal amino acid residue of the B chain or to the ε-amino group of a Lys residue present in the B chain of the parent insulin;
• wherein X is:
• —CO—;
• —COCH(COOH)CO—;
• —CON(CH2COOH)CH2CO—;
• —CON(CH2COOH)CH2CON(CH2COOH)CH2CO—;
• —CON(CH2CH2COOH)CH2CH2CO—;
• —CON(CH2CH2COOH)CH2CH2CON(CH2CH2COOH)CH2CH2CO—;
• —CONHCH(COOH)(CH2)4NHCO—;
• —CON(CH2CH2COOH)CH2CO—;
• or
• —CON(CH2COOH)CH2CH2CO—;
• that
• a) when W is an amino acid residue or a chain of amino acid residues, via a bond from the underscored carbonyl carbon forms an amide bond with an amino group in W, or
• b) when W is a covalent bond, via a bond from the underscored carbonyl carbon forms an amide bond with the N-terminal α-amino group in the B chain or with the ε-amino group of a Lys residue present in the B chain of the parent insulin;
• wherein Y is:
• —(CH2)m— where m is an integer in the range of 6 to 32;
• a divalent hydrocarbon chain comprising 1, 2 or 3 —CH═CH— groups and a number of —CH2— groups sufficient to give a total number of carbon atoms in the chain in the range of 10 to 32;
• a divalent hydrocarbon chain of the formula —(CH2)vC6H4(CH2)W— wherein v and w are integers or one of them is zero so that the sum of v and w is in the range of 6 to 30;
• and wherein Z is:
• —COOH;
• —CO-Asp;
• —CO-Glu;
• —CO-Gly;
• —CO-Sar;
• —CH(COOH)2;
• —N(CH2COOH)2;
• —SO3H;
• or
• —PO3H;
• and any Zn2+ complexes thereof, provided that when W is a covalent bond and X is —CO—, then Z is different from —COOH.