Methods and Compositions for Treating Diabetes

Abstract

Described herein are methods and compositions for treating diabetes mellitus, concerning oral pharmaceutical compositions comprising insulin in combination with a GLP-1 analogue.

1 . An oral pharmaceutical composition, comprising an oil-based liquid formulation, said oral pharmaceutical composition comprising an insulin, a GLP-1 analogue, a trypsin inhibitor, and a chelator of divalent cations, wherein said oil-based liquid formulation is surrounded by a coating that resists degradation in the stomach. 
     
     
         2 . An oral pharmaceutical composition, comprising a combination of i) a first oil-based liquid formulation, said first oil-based liquid formulation comprising an insulin, a trypsin inhibitor, and a chelator of divalent cations; and ii) a second oil-based liquid formulation, said second oil-based liquid formulation comprising a GLP-1 analogue, a trypsin inhibitor, and a chelator of divalent cations, wherein each of said first oil-based liquid formulation and said second oil-based liquid formulation is surrounded by a coating that resists degradation in the stomach. 
     
     
         3 . The oral pharmaceutical composition of  claim 1 , wherein said oil-based liquid formulation, further comprises a component provided as a mixture of (a) a monoacylglycerol, a diacylglycerol, a triacylglycerol, or a mixture thereof; and (b) a polyethylene glycol (PEG) ester of a fatty acid. 
     
     
         4 . The oral pharmaceutical composition of  claim 1 , wherein said oil-based liquid formulation, further comprises a self-emulsifying component. 
     
     
         5 . The oral pharmaceutical composition of  claim 1 , wherein said insulin is present in an amount between 4-12 mg inclusive for an adult patent or a corresponding amount per body weight for a pediatric patient. 
     
     
         6 . The oral pharmaceutical composition of  claim 5 , wherein said GLP-1 analogue is present in an amount between 100-300 micrograms inclusive for an adult patent or a corresponding amount per body weight for a pediatric patient. 
     
     
         7 . The oral pharmaceutical composition of  claim 1 , wherein said GLP-1 analogue is present in an amount between 100-300 micrograms inclusive for an adult patent or a corresponding amount per body weight for a pediatric patient. 
     
     
         8 . The oral pharmaceutical composition of  claim 1 , wherein said trypsin inhibitor is selected from the group consisting of soybean trypsin inhibitor (SBTI), Bowman-Birk inhibitor (BBI), and aprotinin. 
     
     
         9 . The oral pharmaceutical composition of  claim 1 , further comprising a second trypsin inhibitor. 
     
     
         10 . The oral pharmaceutical composition of  claim 9 , wherein said first and second trypsin inhibitors are (i) SBTI and (ii) aprotinin; or said first and second trypsin inhibitors are (i) isolated KTI3 and (ii) isolated BBI. 
     
     
         11 . The oral pharmaceutical composition of  claim 1 , wherein said chelator is EDTA. 
     
     
         12 . The oral pharmaceutical composition of  claim 1 , wherein said oil is fish oil. 
     
     
         13 . The oral pharmaceutical composition of  claim 1 , wherein said oil-based liquid formulation is water-free. 
     
     
         14 . The oral pharmaceutical composition of  claim 1 , wherein said GLP-1 analogue is exenatide. 
     
     
         15 . The oral pharmaceutical composition of  claim 1 , wherein said coating is a pH-sensitive capsule. 
     
     
         16 . The oral pharmaceutical composition of  claim 1  for reducing preprandial glucose excursion in a having human Type 2 diabetes mellitus. 
     
     
         17 . The oral pharmaceutical composition of  claim 16 , wherein said insulin is present in an amount between 4-12 mg inclusive, said GLP-1 analogue is exenatide, and said exenatide is present in an amount between 100-300 micrograms inclusive. 
     
     
         18 . Use of the oral pharmaceutical composition of  claim 1  for reducing preprandial glucose excursion in a having human Type 2 diabetes mellitus. 
     
     
         19 . A method for treating a human with Type 2 diabetes mellitus, said method comprising the steps of selecting a subject diagnosed with Type 2 diabetes mellitus, and administering said subject oral pharmaceutical composition of  claim 1 , thereby treating a human with Type 2 diabetes mellitus. 
     
     
         20 . A method for treating a non-human animal with diabetes mellitus, said method comprising the step of administering to said non-human animal the oral pharmaceutical composition of  claim 1 , thereby treating a non-human animal with diabetes mellitus. 
     
     
         21 . A method for reducing preprandial glucose excursion in a human with Type 2 diabetes mellitus, said method comprising the steps of selecting a subject diagnosed with Type 2 diabetes mellitus, and administering said subject oral pharmaceutical composition of  claim 1 , thereby reducing preprandial glucose excursion in a human with Type 2 diabetes mellitus. 
     
     
         22 . A method for reducing preprandial glucose excursion in a non-human animal with diabetes mellitus, said method comprising the step of administering to said non-human animal the oral pharmaceutical composition of  claim 1 , thereby reducing preprandial glucose excursion in a non-human animal with diabetes mellitus.