Method of lowering cholesterol and triglycerides by administering exendins
View Patent ↗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. A method for lowering total cholesterol levels, LDL-cholesterol levels, or triglyceride levels in a human in need thereof comprising: identifying a human in need of a reduction in total cholesterol levels, LDL-cholesterol levels, or triglyceride levels; 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 reduce total cholesterol levels, LDL-cholesterol levels, or triglyceride levels 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.
2. The method of claim 1 , wherein the exendin or exendin analog agonist is (i) exendin-4 or (ii) a peptide having at least 90% sequence identity to exendin 4.
3. The method of claim 1 , 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.
4. The method of claim 3 , 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.
5. The method of claim 1 , 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.
6. The method of claim 1 , wherein the formulation is an oleaginous suspension.