Compositions and methods for increasing insulin sensitivity

Abstract

Methods and compositions for treating a blood glucose condition involve identifying a suitable subject and administering an effective amount of a composition that contains one or more of an opioid antagonist, an anticonvulsant, and a psychotherapeutic agent. The compositions can include insulin. In some embodiments, such methods and compositions can be used to modulate a blood glucose level. In preferred embodiments, such methods and compositions are useful for increasing a subject's sensitivity to insulin.

What is claimed is: 
     
         1 . A method of treating a blood-glucose condition, comprising:
 identifying a subject having a blood-glucose condition in need of treatment; and   administering to the subject an amount of a composition that is effective to modulate a blood glucose level, wherein the composition comprises at least one selected from:   a non-sulfamate anticonvulsant;   a psychotherapeutic agent;   an opioid antagonist;   a combination of a psychotherapeutic agent and an opioid antagonist;   a combination of a psychotherapeutic agent and an anticonvulsant;   a combination of an opioid antagonist and an anticonvulsant; and   a combination of an opioid antagonist, an anticonvulsant, and a psychotherapeutic agent.   
     
     
         2 . The method of  claim 1 , wherein the subject suffers from at least one condition selected from diabetes, insulin resistance, hyperinsulinemia, impaired glucose metabolism, and hyperglycemia. 
     
     
         3 . The method of  claim 2 , wherein the condition is insulin resistance. 
     
     
         4 . The method of  claim 2 , wherein the condition is Type 2 diabetes. 
     
     
         5 . The method of  claim 1 , wherein the psychotherapeutic agent is selected from: amitriptyline, aripiprazole, benzodiazepines, bupropion, carbamezepine, clomipramine, clozapine, desipramine, dothiapen, doxepin, elatriptan, other triptans, fluoxetine, imipramine, lamotrogine, lithium, maprotiline, mirtazapine, nortriptyline, olanzapine, oxycarbamezepine, paroxetine, protriptyline, quetiapine, risperidone, setiptiline, sumatriptan, tiagabine, trimipramine, valproate, ziprasidone, and zolmitriptan, or a pharmaceutically-acceptable salt or prodrug thereof. 
     
     
         6 . The method of  claim 5 , wherein the psychotherapeutic agent is selected from: bupropion, mirtazapine, olanzapine, setiptiline, fluoxetine, and valproate, or a pharmaceutically-acceptable salt or prodrug thereof. 
     
     
         7 . The method of  claim 1 , wherein the anticonvulsant is selected from: 5,5-diphenylhydantoin, benzodiazepine, carbamazepine, clonazepam, clorazepate, diazepam, divalproex, ethosuximide, felbamate, fosphenytoin, gabapentin, lamotrigine, levetiracetam, methsuximide, oxcarbazepine, phenytoin, pregabalin, tiagabine, topiramate, valproate, valproic acid, and zonisamide, or a pharmaceutically-acceptable salt or prodrug thereof. 
     
     
         8 . The method of  claim 1 , wherein the non-sulfamate anticonvulsant is selected from zonisamide, valproate, and valproic acid, or a pharmaceutically-acceptable salt or prodrug thereof. 
     
     
         9 . The method of  claim 1 , wherein the anticonvulsant is zonisamide. 
     
     
         10 . The method of  claim 1 , wherein the opioid antagonist is selected from: alvimopan, buprenorphine, lofexidine, nalmefene, nalorphine, naloxone, naltrexone, norbinaltorphimine, methylnaltrexone, pentacozine, and propiram, or a pharmaceutically-acceptable salt or prodrug thereof. 
     
     
         11 . The method of  claim 10 , wherein the opioid antagonist is selected from: nalmefene, nalorphine, naloxone, naltrexone, and methylnaltrexone, or a pharmaceutically-acceptable salt or prodrug thereof. 
     
     
         12 . The method of  claim 1 , wherein the composition comprises a combination of a psychotherapeutic agent and an opioid antagonist. 
     
     
         13 . The method of  claim 12 , wherein the psychotherapeutic agent is selected from bupropion, mirtazapine, olanzapine, setiptiline, fluoxetine, and valproate, or a pharmaceutically-acceptable salt or prodrug thereof; and wherein the opioid antagonist is selected from nalmefene, nalorphine, naloxone, naltrexone, and methylnaltrexone, or a pharmaceutically-acceptable salt or prodrug thereof. 
     
     
         14 . The method of  claim 12 , wherein the psychotherapeutic agent is administered to the subject separately from the opioid antagonist. 
     
     
         15 . The method of  claim 1 , wherein the composition comprises a combination of a psychotherapeutic agent and an anticonvulsant. 
     
     
         16 . The method of  claim 15 , wherein the psychotherapeutic agent is selected from bupropion, mirtazapine, olanzapine, setiptiline, fluoxetine, and valproate, or a pharmaceutically-acceptable salt or prodrug thereof; and wherein the anticonvulsant is selected from topiramate, valproate, valproic acid, and zonisamide, or a pharmaceutically-acceptable salt or prodrug thereof. 
     
     
         17 . The method of  claim 15 , wherein the psychotherapeutic agent is administered to the subject separately from the anticonvulsant. 
     
     
         18 . The method of  claim 1 , wherein the composition comprises a combination of an opioid antagonist and an anticonvulsant. 
     
     
         19 . The method of  claim 18 , wherein the opioid antagonist is selected from: alvimopan, buprenorphine, lofexidine, nalmefene, nalorphine, naloxone, naltrexone, norbinaltorphimine, methylnaltrexone, pentacozine, and propiram, or a pharmaceutically-acceptable salt or prodrug thereof; and wherein the anticonvulsant is selected from topiramate, valproate, valproic acid, and zonisamide, or a pharmaceutically-acceptable salt or prodrug thereof. 
     
     
         20 . The method of  claim 18 , wherein the opioid antagonist is administered to the subject separately from the anticonvulsant. 
     
     
         21 . The method of  claim 1 , wherein the composition comprises a combination of an opioid antagonist, an anticonvulsant, and a psychotherapeutic agent. 
     
     
         22 . The method of  claim 21 , wherein the opioid antagonist is selected from: alvimopan, buprenorphine, lofexidine, nalmefene, nalorphine, naloxone, naltrexone, norbinaltorphimine, methylnaltrexone, pentacozine, and propiram, or a pharmaceutically-acceptable salt or prodrug thereof; wherein the anticonvulsant is selected from topiramate, valproate, valproic acid, and zonisamide, or a pharmaceutically-acceptable salt or prodrug thereof; and wherein the psychotherapeutic agent is selected from bupropion, mirtazapine, olanzapine, setiptiline, fluoxetine, and valproate, or a pharmaceutically-acceptable salt or prodrug thereof. 
     
     
         23 . The method of  claim 21 , wherein at least one of the opioid antagonist, an anticonvulsant, and a psychotherapeutic agent is administered to the subject separately from at least one of the others. 
     
     
         24 . The method of  claim 1 , wherein the composition further comprises insulin. 
     
     
         25 . The method of  claim 1 , wherein the composition comprises a controlled release formulation. 
     
     
         26 . The method of  claim 25 , wherein the controlled release formulation is a sustained release formulation. 
     
     
         27 . The method of  claim 1 , further comprising obtaining a measurement of the subject's blood glucose level. 
     
     
         28 . The method of  claim 27 , further comprising adjusting a dosage of the composition after obtaining the measurement of the subject's blood glucose level. 
     
     
         29 . The method of  claim 1 , further comprising providing dietary instructions to the subject. 
     
     
         30 . A package comprising:
 a blood glucose-modulating composition in unit dosage form; and   written instructions advising the reader to monitor the blood glucose level of an intended human recipient of the composition;   wherein the blood glucose-modulating composition comprises at least one selected from:   a non-sulfamate anticonvulsant;   a psychotherapeutic agent;   an opioid antagonist;   a combination of a psychotherapeutic agent and an opioid antagonist;   a combination of a psychotherapeutic agent and an anticonvulsant;   a combination of an opioid antagonist and an anticonvulsant; and   a combination of an opioid antagonist, an anticonvulsant, and a psychotherapeutic agent.