Exendins to lower cholesterol and triglycerides

Abstract

Provided herein are pharmaceutical formulations containing exendins, exendin agonists, or exendin analog agonists that are administered at therapeutic plasma concentration levels over a sustained period of time to lower total cholesterol levels; to lower LDL-cholesterol levels; to lower triglyceride levels; to treat dyslipidemia; to treat and slow the progression of atherosclerosis; and to treat, prevent, and reduce the risk of heart attacks and strokes in patients. In the pharmaceutical formulations and methods of the invention, the exendin may be exendin-4, an exendin-4 agonist, or an exendin-4 analog agonist. The pharmaceutical formulations may be polymer-based pharmaceutical formulations that may be administered once weekly. An exemplary pharmaceutical formulation comprises 5% (w/w) of exenatide, about 2% (w/w) of sucrose, and about 93% (w/w) of a poly(lactide-co-glycolide) polymer, wherein the poly(lactide-co-glycolide) polymer is in the form of microspheres encapsulating the exenatide.

1 .- 19 . (canceled) 
     
     
         20 . A method for treating dyslipidemia or atherosclerosis in a human in need thereof comprising:
 identifying a human in need of a treatment for dyslipidemia or atherosclerosis; and   administering to the human a pharmaceutical formulation comprising at least one exendin or exendin analog agonist once per week in an amount sufficient to maintain a steady state geometric mean plasma concentration of the exendin or exendin analog agonist of 145 pg/mL to 700 pg/mL to treat the dyslipidemia or atherosclerosis in the patient, wherein the amount is about 2.0 mg to about 5 mg, and wherein a dosage of the formulation comprises about 5% (w/w) of exenatide, about 2% (w/w) of sucrose, and about 93% (w/w) of a poly(lactide-co-glycolide) polymer.   
     
     
         21 . The method of  claim 20 , wherein the exendin or exendin analog agonist is (i) exendin-4 or (ii) a peptide having at least 90% sequence identity to exendin 4. 
     
     
         22 . The method of  claim 20 , wherein the steady state geometric mean plasma concentration of the exendin or exendin analog agonist is at a level of 175 pg/mL to 650 pg/mL. 
     
     
         23 . The method of  claim 20 , wherein the steady state geometric mean plasma concentration of the exendin or exendin analog agonist is at a level of 200 pg/mL to 600 pg/mL. 
     
     
         24 . The method of  claim 20 , wherein the steady state geometric mean plasma concentration of the exendin or exendin analog agonist is at the steady state for about one week to about three months. 
     
     
         25 . The method of  claim 20 , wherein the formulation is an oleaginous suspension.