Treatment for diabetes in patients with insufficient glycemic control despite therapy with an oral antidiabetic drug

Abstract

The present invention relates to the finding that certain DPP-4 inhibitors are particularly suitable for treating and/or preventing metabolic diseases, particularly diabetes, in patients with insufficient glycemic control despite a therapy with an oral and/or a non-oral antidiabetic drug.

What is claimed is: 
     
         1 . A method for treating metabolic diseases in type 2 diabetes patients with insufficient glycemic control despite therapy with one or more oral or non-oral antidiabetic drugs selected from metformin, sulphonylureas, thiazolidinediones, glinides, α-glucosidase inhibitors, GLP-1 or GLP-1 analogues, and insulin or insulin analogues, the method comprising
 administering a DPP-4 inhibitor which is 1-[(4-methyl-quinazolin-2-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-(3-(R)-amino-piperidin-1-yl)-xanthine, or a pharmaceutically acceptable salt thereof, in an oral daily amount of 5 mg, 
 wherein said 1-[(4-methyl-quinazolin-2-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-(3-(R)-amino-piperidin-1-yl)-xanthine, or a pharmaceutically acceptable salt thereof, is used in combination with one or more oral or non-oral antidiabetic drugs. 
 
     
     
         2 . The method according to  claim 1 , wherein said one or more oral antidiabetic drugs is selected from metformin, sulphonylureas, thiazolidinediones, glinides and α-glucosidase inhibitors. 
     
     
         3 . The method according to  claim 1 , wherein said one or more oral antidiabetic drugs is a sulphonylurea drug. 
     
     
         4 . The method according to  claim 1 , wherein said one or more oral antidiabetic drugs is a sulphonylurea drug alone. 
     
     
         5 . The method according to  claim 1 , wherein said one or more oral antidiabetic drugs are a sulphonylurea drug and metformin. 
     
     
         6 . The method according to  claim 1 , wherein said DPP-4 inhibitor is used in combination with said sulphonylurea, and, optionally, in combination with one or more other therapeutic agents selected from metformin and a thiazolidinedione. 
     
     
         7 . The method according to  claim 1 , wherein said DPP-4 inhibitor is used as replacement of said sulphonylurea, and, optionally, in combination with one or more other therapeutic agents. 
     
     
         8 . The method according to  claim 1 , wherein said DPP-4 inhibitor is used in add-on combination therapy with said sulphonylurea. 
     
     
         9 . The method according to  claim 1 , for improving HbA1c, FPG or PPG, decreasing glucose excursion, or improving insulin secretion in said patients, or any combination of the foregoing conditions. 
     
     
         10 . The method according to  claim 1 , in patients with indication on first- or second-line sulphonylurea therapy. 
     
     
         11 . The method according to  claim 1 , for the treatment of diabetes in patients with indication on dual sulphonylurea combination therapy. 
     
     
         12 . The method according to  claim 1 , for the treatment of diabetes in patients with indication on triple sulphonylurea combination therapy. 
     
     
         13 . The method according to  claim 1 , for the treatment of diabetes in patients with indication on insulin therapy. 
     
     
         14 . The method according  claim 1 , wherein said patients suffer from inadequate HbA1c values from 7.0 to 11%, despite therapy with a sulphonylurea drug. 
     
     
         15 . The method according to  claim 1 , for reducing the risk for adverse effects associated with sulphonylurea antidiabetic therapy selected from hypoglycaemia, weight gain, and a combination thereof, in said patients. 
     
     
         16 . The method according to  claim 1 , wherein said patients are renally impaired and/or elderly patients. 
     
     
         17 . The method according to  claim 1 , wherein said DPP-4 inhibitor is 1-[(4-methyl-quinazolin-2-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-(3-(R)-amino-piperidin-1-yl)-xanthine in free base form. 
     
     
         18 . The method according to  claim 1 , wherein said patients are patients with insufficient glycemic control despite mono-therapy with metformin, a sulphonylurea, pioglitazone or (basal) insulin, or despite dual combination therapy with a metformin/pioglitazone, metformin/sulphonylurea, metformin/(basal) insulin, sulphonylurea/pioglitazone, sulphonylurea/(basal) insulin or pioglitazone/(basal) insulin combination. 
     
     
         19 . The method according to  claim 1  for treating type 2 diabetes in a patient with insufficient glycemic control despite therapy with one antihyperglycemic agent selected from metformin, sulphonylureas, thiazolidinediones, glinides, α-glucosidase inhibitors, GLP-1 and GLP-1 analogues, and insulin and insulin analogues, said method comprising administering 1-[(4-methyl-quinazolin-2-yl)methyl]-3-methyl-7-(2-butyn-1-yl)-8-(3-(R)-amino-piperidin-1-yl)-xanthine in an oral daily amount of 5 mg in combination with said one antihyperglycemic agent to the patient. 
     
     
         20 . The method according to  claim 1  for treating type 2 diabetes in a patient with insufficient glycemic control despite therapy with two antihyperglycemic agents selected from metformin, sulphonylureas, thiazolidinediones, glinides, α-glucosidase inhibitors, GLP-1 and GLP-1 analogues, and insulin and insulin analogues, said method comprising administering 1-[(4-methyl-quinazolin-2-yl)methyl]-3-methyl-7-(2-Butyn-1-yl)-8-(3-(R)-amino-piperidin-1-yl)-xanthine in an oral daily amount of 5 mg in combination with said two antihyperglycemic agents to the patient. 
     
     
         21 . The method according to  claim 1 , for achieving a reduction in the dose of said one or more oral or non-oral antidiabetic drugs required for adequate therapeutic effect. 
     
     
         22 . The method according to  claim 1 , wherein the 5 mg is administered once daily, with or without food. 
     
     
         23 . The method according to  claim 1 , wherein the patient has renal impairment. 
     
     
         24 . The method according to  claim 23 , wherein no adjustment of the daily dose of the DPP-4 inhibitor is required. 
     
     
         25 . The method according to  claim 22 , wherein steady state plasma levels of the DPP-4 inhibitor are reached between second and fifth day of administration.