Methods and Compositions for the Treatment of Metabolic Disorders and Diseases

Abstract

Provided herein are variants and fusions of fibroblast growth factor 19 (FGF19), variants and fusions of fibroblast growth factor 21 (FGF21), fusions of FGF19 and/or FGF21, and variants or fusions of FGF19 and/or FGF21 proteins and peptide sequences (and peptidomimetics), having one or more activities, such as glucose lowering activity, and methods for and uses in treatment of hyperglycemia and other disorders.

1 .- 81 . (canceled) 
     
     
         82 . A peptide having an amino acid sequence comprising or consisting of SEQ ID NO: 198, SEQ ID NO: 199, SEQ ID NO:200, SEQ ID NO: 201, SEQ ID NO:202, or SEQ ID NO:203. 
     
     
         83 . A pharmaceutical composition, comprising the peptide of  claim 82  and a pharmaceutically acceptable carrier. 
     
     
         84 . A pharmaceutical composition, comprising the peptide of  claim 82 , a glucose lowering agent, and a pharmaceutically acceptable carrier. 
     
     
         85 . A method of treating a subject having a hyperglycemic condition, comprising administering an effective amount of the peptide of  claim 82  to the subject. 
     
     
         86 . The method of  claim 85 , wherein the method further comprises supplementary therapy. 
     
     
         87 . The method of  claim 86 , wherein the supplementary therapy is a weight loss surgery. 
     
     
         88 . The method of  claim 86 , wherein the supplementary therapy is a gastric bypass, gastrectomy, gastric banding, gastric balloon, or gastric sleeve. 
     
     
         89 . The method of  claim 86 , wherein the supplementary therapy is administration of a glucose lowering agent, insulin, GLP1 analogue, biguanide, sulphonylurea, thiazolidinedione, a dipeptidyl peptidase-4 (DPP-4) inhibitor, a bromocriptine formulation, a bile acid sequestrant, metformin, a thiazolidinedione (TZD), a SGLT-2 inhibitor, or any combination thereof. 
     
     
         90 . The method of  claim 86 , wherein the supplementary therapy is provided prior to said method. 
     
     
         91 . The method of  claim 86 , wherein the supplementary therapy is provided contemporaneously with said method. 
     
     
         92 . The method of  claim 86 , wherein the supplementary therapy is provided following said method. 
     
     
         93 . The method of  claim 85 , wherein the hyperglycemic condition comprises diabetes. 
     
     
         94 . The method of  claim 85 , wherein the hyperglycemic condition comprises insulin-dependent (type I) diabetes, type II diabetes, or gestational diabetes. 
     
     
         95 . The method of  claim 85 , wherein the hyperglycemic condition comprises obesity. 
     
     
         96 . A method of reducing glucose levels in a subject in need thereof, comprising administering an effective amount of the peptide of  claim 82  to the subject. 
     
     
         97 . The method of  claim 96 , wherein the subject has a fasting plasma glucose level greater than 100 mg/dl or has a hemoglobin A1c (HbA1c) level above 6%. 
     
     
         98 . The method of  claim 96 , wherein the subject has a hyperglycemic condition, insulin resistance, hyperinsulinemia, glucose intolerance or metabolic syndrome. 
     
     
         99 . The method of  claim 96 , wherein the subject has diabetes or obesity. 
     
     
         100 . The method of  claim 96 , wherein the subject has insulin-dependent (type I) diabetes, type II diabetes, or gestational diabetes. 
     
     
         101 . A nucleic acid encoding the peptide of  claim 82 .