Combination therapy comprising anti-diabetic and anticonvulsant agents

Abstract

Combination therapy comprising anti-diabetic agents and anticonvulsant derivatives useful for the treatment of Type II diabetes mellitus and Syndrome X are disclosed.

What is claimed is:  
     
         1 . A method for treating Type II diabetes mellitus in mammals afflicted with such condition comprising administering to said mammal a therapeutically effective amount of a compound of the formula I:  
       
         
           
           
               
               
           
         
         wherein  
         X is CH 2  or oxygen;  
         R 1  is hydrogen or alkyl; and  
         R 2 , R 3 , R 4  and R 5  are independently hydrogen or lower alkyl and, when X is CH 2 , R 4  and R 5  may be alkene groups joined to form a benzene ring and, when X is oxygen, R 2  and R 3  and/or R 4  and R 5  together may be a methylenedioxy group of the following formula (II):  
         
           
             
             
                 
                 
             
           
         
         wherein  
         R 6  and R 7  are the same or different and are hydrogen, lower alkyl or are alkyl and are joined to form a cyclopentyl or cyclohexyl ring;  
         in combination with a therapeutically effective amount of one or more anti-diabetic agent.  
       
     
     
         2 . The method of  claim 1  wherein the compound of formula I is topiramate.  
     
     
         3 . The method of  claim 1 , wherein the therapeutically effective amount of the compound of formula I is from about 32 to 512 mg.  
     
     
         4 . The method of  claim 1 , wherein the therapeutically effective amount of the compound of formula I is of from about 16 to 256 mg once or twice daily.  
     
     
         5 . The method of  claim 1  wherein the anti-diabetic agent is selected from the group consisting of a sulfonylurea, a meglitinide, an agents which modify insulin secretion, a biguanide, a thiazolidinedione, a peroxisome proliferator-activated receptor-gamma agonist (PPAR-gamma), a Retinoid-X receptor (RXR) modulator, an insulin sensitizing agent, an alpha-glucosidase inhibitor, an insulin, a small molecule mimics of insulin, Na a-glucose co-transporter inhibitor, an amylin agonists and a glucagon antagonist.  
     
     
         6 . The method of  claim 1  wherein the anti-diabetic agent is selected from the group consisting of metformin, a sulfonylureas, a thiazolidinediones and insulin.  
     
     
         7 . A method of treating Syndrome X (Insulin Resistance Syndrome, Metabolic Syndrome, or Metabolic Syndrome X) in mammals afflicted with such condition comprising administering to said mammal a therapeutically effective amount of a compound of the formula I:  
       
         
           
           
               
               
           
         
         wherein  
         X is CH 2  or oxygen;  
         R 1  is hydrogen or alkyl; and  
         R 2 , R 3 , R 4  and R 5  are independently hydrogen or lower alkyl and, when X is CH 2 , R 4  and R 5  may be alkene groups joined to form a benzene ring and, when X is oxygen, R 2  and R 3  and/or R 4  and R 5  together may be a methylenedioxy group of the following formula (II):  
         
           
             
             
                 
                 
             
           
         
         wherein  
         R 6  and R 7  are the same or different and are hydrogen, lower alkyl or are alkyl and are joined to form a cyclopentyl or cyclohexyl ring;  
         in combination with a therapeutically effective amount of one or more anti-diabetic agent.  
       
     
     
         8 . The method of  claim 8  wherein the compound of formula I is topiramate.  
     
     
         9 . The method of  claim 8 , wherein the therapeutically effective amount of the compound of formula I is from about 32 to 512 mg.  
     
     
         10 . The method of  claim 8 , wherein the therapeutically effective amount of the compound of formula I is of from about 16 to 256 mg once or twice daily.  
     
     
         11 . The method of  claim 8  wherein the anti-diabetic agent is selected from the group consisting of a sulfonylurea, a meglitinide, an agents which modify insulin secretion, a biguanide, a thiazolidinedione, a peroxisome proliferator-activated receptor-gamma agonist (PPAR-gamma), a Retinoid-X receptor (RXR) modulator, an insulin sensitizing agent, an alpha-glucosidase inhibitor, an insulin, a small molecule mimics of insulin, Na a-glucose co-transporter inhibitor, an amylin agonists and a glucagon antagonist.  
     
     
         12 . The method of  claim 1  wherein the anti-diabetic agent is selected from the group consisting of metformin, a sulfonylureas, a thiazolidinediones and insulin.