Combinations of vanadium with antidiabetics for glucose metabolism disorders

Abstract

Compositions and methods of using the same for the treatment of diabetes and other disorders of glucose metabolism are provided. Compositions may include an anti-diabetic agent and one or more of a bioavailable source of chromium and vanadium.

1 . A composition comprising an anti-diabetic agent and a bioavailable source of chromium.  
     
     
         2 . A composition comprising an anti-diabetic agent and a bioavailable source of chromium, whereby said composition reduces initial Hb1Ac levels observed in a patient by at least a 10% change from the baseline after treatment.  
     
     
         3 . A composition comprising an anti-diabetic agent and a bioavailable source of chromium, whereby said composition reduces initial Hb1Ac levels observed in a patient by at least a 50% change from the baseline after treatment.  
     
     
         4 . The composition of  claim 1 , wherein said bioavailable source of chromium comprises one or more of chromium picolinate or chromium polynicotinate.  
     
     
         5 . The composition of  claim 1 , wherein said anti-diabetic agent comprises a type of anti-diabetic agent selected from the group consisting of insulin, thiazolidinediones, sulfonylureas, benzoic acid derivatives, and alpha-glucosidase inhibitors.  
     
     
         6 . The composition of  claim 1 , wherein said anti-diabetic agent is metformin.  
     
     
         7 . The composition of  claim 6 , wherein metformin is in the range of about 100 mg up to about 2550 mg per dose.  
     
     
         8 . The composition of  claim 1 , wherein said anti-diabetic agent is a sulfonylurea.  
     
     
         9 . A composition according to  claim 8 , wherein said sulfonylurea is acetohexamide, chlorpropamide, tolazimide, tolbutamide, glycazide, glipizide, glyburide, or glimeperide.  
     
     
         10 . A composition according to  claim 1 , wherein said anti-diabetic agent is a thiazolidinedione.  
     
     
         11 . A composition according to  claim 10 , wherein said thiazolidinedione is troglitazone, rosiglitazone, or pioglitazone.  
     
     
         12 . A composition according to  claim 1 , wherein said anti-diabetic agent is an alpha-glucosidase inhibitor.  
     
     
         13 . A composition according to  claim 12 , wherein said alpha-glucosidase inhibitor is acarbose or miglitol.  
     
     
         14 . A composition according to  claim 1 , wherein said anti-diabetic agent is a benzoic acid derivative.  
     
     
         15 . A composition according to  claim 14 , wherein said benzoic acid derivative is repaglinide.  
     
     
         16 . The composition of  claim 1 , wherein said bioavailable source of chromium comprises more than 300 mcg elemental chromium.  
     
     
         17 . The composition of  claim 1 , further comprising an effective amount of a bioavailable source of vanadium.  
     
     
         18 . The composition of  claim 17 , wherein said bioavailable source of vanadium is vanadyl sulfate.  
     
     
         19 . The composition of  claim 1 , further comprising an effective amount of a bioavailable source of one or more of the following: chromium, magnesium, and aspirin.  
     
     
         20 . A composition comprising an anti-diabetic agent and a bioavailable source of vanadium.  
     
     
         21 . A composition comprising an anti-diabetic agent and a bioavailable source of vanadium, whereby said composition reduces initial Hb1Ac levels observed in a patient by at least a 10% change from the baseline after treatment.  
     
     
         22 . A composition comprising an anti-diabetic agent and a bioavailable source of vanadium, whereby said composition reduces initial Hb1Ac levels observed in a patient by at least a 50% change from the baseline after treatment.  
     
     
         23 . The composition of  claim 20 , wherein said anti-diabetic agent comprises a type of anti-diabetic agent selected from the group consisting of insulin, thiazolidinediones, sulfonylureas, benzoic acid derivatives, and alpha-glucosidase inhibitors.  
     
     
         24 . The composition of  claim 20 , wherein said anti-diabetic agent is metformin.  
     
     
         25 . The composition of  claim 24 , wherein metformin is in the range of about 100 mg up to about 2550 mg per dose.  
     
     
         26 . The composition of  claim 20 , wherein said anti-diabetic agent is a sulfonylurea.  
     
     
         27 . A composition according to  claim 26 , wherein said sulfonylurea is acetohexamide, chlorpropamide, tolazimide, tolbutamide, glycazide, glipizide, glyburide, or glimeperide.  
     
     
         28 . A composition according to  claim 20 , wherein said anti-diabetic agent is a thiazolidinedione.  
     
     
         29 . A composition according to  claim 28 , wherein said thiazolidinedione is troglitazone, rosiglitazone or pioglitazone.  
     
     
         30 . A composition according to  claim 20 , wherein said anti-diabetic agent is an alpha-glucosidase inhibitor.  
     
     
         31 . A composition according to  claim 30 , wherein said alpha-glucosidase inhibitor is acarbose or miglitol.  
     
     
         32 . A composition according to  claim 20 , wherein said anti-diabetic agent is a benzoic acid derivative.  
     
     
         33 . A composition according to  claim 32 , wherein said benzoic acid derivative is repaglinide.  
     
     
         34 . The composition of  claim 20 , wherein said bioavailable source of vanadium is vanadyl sulfate.  
     
     
         35 . The composition of  claim 20 , wherein said bioavailable source of vanadium comprises more than 10 mg elemental vanadium.  
     
     
         36 . The composition of  claim 20 , further comprising an effective amount of a bioavailable source of chromium, wherein said bioavailable source of chromium is chromium polynicotinate.  
     
     
         37 . The composition of  claim 20 , further comprising an effective amount of a bioavailable source of one or more of the following: chromium, magnesium, and aspirin.  
     
     
         38 . A method for improving glucose metabolism, comprising administering to a patient an anti-diabetic agent and bioavailable source of chromium.  
     
     
         39 . The method of  claim 38 , wherein said bioavailable source of chromium comprises one or more of chromium picolinate or chromium polynicotinate.  
     
     
         40 . The method of  claim 38 , wherein said anti-diabetic agent comprises a type of anti-diabetic agent selected from the group consisting of insulin, thiazolidinediones, sulfonylureas, benzoic acid derivatives, and alpha-glucosidase inhibitors.  
     
     
         41 . The method of  claim 38 , wherein said anti-diabetic agent is metformin.  
     
     
         42 . The method of  claim 38 , wherein said bioavailable source of chromium comprises more than 300 mcg elemental chromium.  
     
     
         43 . The method of  claim 38 , further comprising administering an effective amount of a bioavailable source of vanadium.  
     
     
         44 . The method of  claim 38 , wherein said bioavailable source of vanadium is vanadyl sulfate.  
     
     
         45 . The method of  claim 38 , further comprising an effective amount of a bioavailable source of one or more of the following: vanadium, magnesium, and aspirin.  
     
     
         46 . A method for improving glucose metabolism, comprising administering to a patient an anti-diabetic agent and bioavailable source of vanadium.  
     
     
         47 . The method of  claim 46 , wherein said bioavailable source of vanadium comprises vanadyl sulfate.  
     
     
         48 . The method of  claim 46 , wherein said anti-diabetic agent comprises a type of anti-diabetic agent selected from the group consisting of insulin, thiazolidinediones, sulfonylureas, benzoic acid derivatives, and alpha-glucosidase inhibitors.  
     
     
         49 . The method of  claim 46  wherein said anti-diabetic agent is metformin.  
     
     
         50 . The method of  claim 46 , wherein said anti-diabetic agent is a thiazolidinedione.  
     
     
         51 . The method of  claim 50 , wherein said thiazolidinedione is troglitazone, rosiglitazone, or pioglitazone.  
     
     
         52 . The method of  claim 46 , further comprising an effective amount of a bioavailable source of one or more of the following: vanadium, magnesium, and aspirin.  
     
     
         53 . An ingestible formulation for improving glucose metabolism in a subject with abnormal glucose metabolism, comprising: 
 (a) a bioavailable source of chromium in a complex and amount that delivers an effective amount of chromium for improving glucose metabolism; and    (b) an anti-diabetic agent.    
     
     
         54 . The ingestible formulation of  claim 53 , wherein said amount of said bioavailable source of chromium is no less than 200 mcg of elemental chromium.  
     
     
         55 . The ingestible formulation of  claim 53 , further comprising an effective amount of one or more of the following: aspirin, Vitamin E, and magnesium.  
     
     
         56 . The ingestible formulation of  claim 53 , wherein said anti-diabetic agent comprises a type of anti-diabetic agent selected from the group consisting of insulin, thiazolidinediones, sulfonylureas, benzoic acid derivatives, and alpha-glucosidase inhibitors.  
     
     
         57 . The ingestible formulation of  claim 53 , wherein said anti-diabetic agent is metformin.  
     
     
         58 . An ingestible formulation for improving glucose metabolism in a subject with abnormal glucose metabolism, comprising: 
 (a) a bioavailable source of vanadium in a complex and amount that delivers an effective amount of vanadium for improving glucose metabolism; and    (b) an anti-diabetic agent.    
     
     
         59 . The ingestible formulation of  claim 58 , wherein said amount of said bioavailable source of vanadium is no less than 5 mg of elemental vanadium.  
     
     
         60 . The ingestible formulation of  claim 58 , further comprising an effective amount of one or more of the following: aspirin, Vitamin E, and magnesium.  
     
     
         61 . The ingestible formulation of  claim 58 , wherein said anti-diabetic agent comprises a type of anti-diabetic agent selected from the group consisting of insulin, thiazolidinediones, sulfonylureas, benzoic acid derivatives, and alpha-glucosidase inhibitors.  
     
     
         62 . The ingestible formulation of  claim 58 , wherein said anti-diabetic agent is metformin.  
     
     
         63 . The use of an ingestible formulation which improves glucose metabolism in a subject for the manufacture of a medicament for the treatment of glucose metabolism disorders, wherein said ingestible formulation comprises a bioavailable source of chromium in a complex and amount that delivers an effective amount of chromium for improving glucose metabolism, and an anti-diabetic agent.  
     
     
         64 . The use of an ingestible formulation which improves glucose metabolism in a subject for the manufacture of a medicament for the treatment of glucose metabolism disorders, wherein said ingestible formulation comprises a bioavailable source of vanadium in a complex and amount that delivers an effective amount of vanadium for improving glucose metabolism, and an anti-diabetic agent.  
     
     
         65 . The use of  claim 63  or  64 , wherein said anti-diabetic agent is selected from the group consisting of insulin, thiazolininediones, sulfonylurease, benzoic acid derivatives, and alpha-glucosidase inhibitors.  
     
     
         66 . The use of an ingestible formulation which improves glucose metabolism in a subject for the development of a regimen for the treatment of glucose metabolism disorders, wherein said ingestible formulation comprises a bioavailable source of chromium in a complex and amount that delivers an effective amount of chromium for improving glucose metabolism, and an anti-diabetic agent.  
     
     
         67 . The use of an ingestible formulation which improves glucose metabolism in a subject for the development of a regimen for the treatment of glucose metabolism disorders, wherein said ingestible formulation comprises a bioavailable source of vanadium in a complex and amount that delivers an effective amount of vanadium for improving glucose metabolism, and an anti-diabetic agent.  
     
     
         68 . The use of  claim 66  or  67 , wherein said anti-diabetic agent is selected from the group consisting of insulin, thiazolininediones, sulfonylurease, benzoic acid derivatives, and alpha-glucosidase inhibitors.  
     
     
         69 . A pill for improving glucose metabolism in a subject with abnormal glucose metabolism, comprising: 
 (a) a bioavailable source of chromium in a complex and amount that delivers an effective amount of chromium for improving glucose metabolism; and    (b) an anti-diabetic agent.    
     
     
         70 . The pill of  claim 69 , wherein said amount of said bioavailable source of chromium is no less than 5 mg of elemental chromium.  
     
     
         71 . The pill of  claim 69 , further comprising an effective amount of one or more of the following: aspirin, Vitamin E, and magnesium.  
     
     
         72 . The pill of  claim 69 , wherein said anti-diabetic agent comprises a type of anti-diabetic agent selected from the group consisting of insulin, thiazolidinediones, sulfonylureas, benzoic acid derivatives, and alpha-glucosidase inhibitors.  
     
     
         73 . The pill of  claim 69 , wherein said anti-diabetic agent is metformin.  
     
     
         74 . A pill for improving glucose metabolism in a subject with abnormal glucose metabolism, comprising: 
 (a) a bioavailable source of vanadium in a complex and amount that delivers an effective amount of vanadium for improving glucose metabolism; and    (b) an anti-diabetic agent.    
     
     
         75 . The pill of  claim 74 , wherein said amount of said bioavailable source of vanadium is no less than 5 mg of elemental vanadium.  
     
     
         76 . The pill of  claim 74 , further comprising an effective amount of one or more of the following: aspirin, Vitamin E, and magnesium.  
     
     
         77 . The pill of  claim 74 , wherein said anti-diabetic agent comprises a type of anti-diabetic agent selected from the group consisting of insulin, thiazolidinediones, sulfonylureas, benzoic acid derivatives, and alpha-glucosidase inhibitors.  
     
     
         78 . The pill of  claim 74 , wherein said anti-diabetic agent is metformin.  
     
     
         79 . The use of a pill which improves glucose metabolism in a subject for the manufacture of a medicament for the treatment of glucose metabolism disorders, wherein said ingestible formulation comprises a bioavailable source of chromium in a complex and amount that delivers an effective amount of chromium for improving glucose metabolism, and an anti-diabetic agent.  
     
     
         80 . The use of a pill which improves glucose metabolism in a subject for the manufacture of a medicament for the treatment of glucose metabolism disorders, wherein said ingestible formulation comprises a bioavailable source of vanadium in a complex and amount that delivers an effective amount of vanadium for improving glucose metabolism, and an anti-diabetic agent.  
     
     
         81 . The use of  claim 79  or  80 , wherein said anti-diabetic agent is selected from the group consisting of insulin, thiazolininediones, sulfonylurease, benzoic acid derivatives, and alpha-glucosidase inhibitors.  
     
     
         82 . The use of a pill which improves glucose metabolism in a subject for the development of a regimen for the treatment of glucose metabolism disorders, wherein said ingestible formulation comprises a bioavailable source of chromium in a complex and amount that delivers an effective amount of chromium for improving glucose metabolism, and an anti-diabetic agent.  
     
     
         83 . The use of a pill which improves glucose metabolism in a subject for the development of a regimen for the treatment of glucose metabolism disorders, wherein said ingestible formulation comprises a bioavailable source of vanadium in a complex and amount that delivers an effective amount of vanadium for improving glucose metabolism, and an anti-diabetic agent.  
     
     
         84 . The use of  claim 82  or  83 , wherein said anti-diabetic agent is selected from the group consisting of insulin, thiazolininediones, sulfonylurease, benzoic acid derivatives, and alpha-glucosidase inhibitors.  
     
     
         85 . A kit for improving glucose metabolism in a subject comprising: 
 (a) an ingestible formulation for improving glucose metabolism in a subject comprising a bioavailable source of chromium in a complex and amount that delivers an effective amount of chromium for improving glucose metabolism, and an anti-diabetic agent; and    (b) instructions for the administration of said ingestible formulation.    
     
     
         86 . The kit of  claim 85 , wherein said instructions provide for the simultaneous administration of chromium and anti-diabetic agent, and provide the daily dosage regiment and duration of treatment.  
     
     
         87 . A kit for improving glucose metabolism in a subject comprising: 
 (c) an ingestible formulation for improving glucose metabolism in a subject comprising a bioavailable source of vanadium in a complex and amount that delivers an effective amount of vanadium for improving glucose metabolism, and an anti-diabetic agent; and    (d) instructions for the administration of said ingestible formulation.    
     
     
         88 . The kit of  claim 87 , wherein said instructions provide for the simultaneous administration of vanadium and anti-diabetic agent, and provide the daily dosage regiment and duration of treatment.  
     
     
         89 . A kit for improving glucose metabolism in a subject comprising: 
 (a) a pill comprising an effective amount of a bioavailable source of chromium a complex and amount that delivers an effective amount of chromium for improving glucose metabolism, and an anti-diabetic agent; and    (b) instructions for the administration of said pill.    
     
     
         90 . The kit of  claim 89 , wherein said instructions provide the daily dosage regimen and the duration of treatment.  
     
     
         91 . A kit for improving glucose metabolism in a subject comprising: 
 (a) a pill comprising an effective amount of a bioavailable source of vanadium in a complex and amount that delivers an effective amount of vanadium for improving glucose metabolism, and an anti-diabetic agent; and    (b) instructions for the administration of said pill.    
     
     
         92 . The kit of  claim 89 , wherein said instructions provide the daily dosage regimen and the duration of treatment.  
     
     
         93 . A kit for improving glucose metabolism in a subject comprising: 
 (a) a bioavailable source of chromium in a complex and amount that delivers an effective amount of chromium for improving glucose metabolism; and    (b) instructions for the administration of said bioavailable source of chromium.    
     
     
         94 . The kit of  claim 93 , wherein said instructions provide for the daily dosage regimen and duration of treatment.  
     
     
         95 . A kit for improving glucose metabolism in a subject comprising: 
 (a) a bioavailable source of vanadium in a complex and amount that delivers an effective amount of vanadium for improving glucose metabolism; and    (b) instructions for the administration of said bioavailable source of vanadium.    
     
     
         96 . The kit of  claim 95 , wherein said instructions provide for the daily dosage regimen and duration of treatment.