Combination treatment of metabolic disorders

1. A method of treating a mammalian subject having a condition selected from the group consisting of insulin resistance syndrome and Type II Diabetes, comprising administering to the subject a Compound of Formula I or a pharmaceutically acceptable salt thereof

wherein:

m is 0, 2 or 4; and

X is —OR 7 , wherein R 7 is hydrogen or alkyl having from 1 to 3 carbon atoms;

R 6 is hydrogen, O or hydroxy; and

three of R 1 , R 2 , R 3 , R 4 and R 5 are hydrogen and the remainder are independently selected from the group consisting of hydrogen, halo, hydroxy, methyl, ethyl, perfluoromethyl, methoxy, ethoxy, and perfluoromethoxy;

or X is —NR 8 R 9 , wherein R 8 is hydrogen or hydroxy and R 9 is hydrogen, methyl or ethyl;

R 6 is hydrogen; and

three of R 1 , R 2 , R 3 , R 4 and R 5 are hydrogen and the remainder are independently selected from the group consisting of hydrogen, halo, methyl, ethyl, perfluoromethyl, methoxy, ethoxy, and perfluoromethoxy;

and a direct PPAR-gamma agonist in a combined amount effective to treat the metabolic condition

wherein the Compound of Formula I or salt thereof is administered in an amount that is less than the usual therapeutic dose when administered alone.

2. The method of claim 1 , wherein the Compound is represented by Formula IA

3. The method of claim 2 , wherein R 1 is methyl and R 5 is methyl.

4. The method of claim 3 , wherein the Compound is 4-(3-(2,6-Dimethylbenzyloxy)phenyl)-4-oxobutyric acid.

5. The method of claim 3 , wherein the Compound is 3-(2,6-Dimethylbenzyloxy)-phenylacetic acid.

6. The method of claim 3 , wherein the Compound is 4-3-(2,6-Dimethylbenzyloxy)-phenyl)-4(R)-hydroxybutanoic acid.

7. The method of claim 3 , wherein the Compound is N-Hydroxy-2-[3-(2,6-dimethylbenzyloxy)phenyl]acetamide.

8. The method of claim 1 , wherein the direct PPAR-gamma agonist is selected from the group consisting of rosiglitazone and pioglitazone, their pharmaceutically acceptable salts, hydrates, and solvates, and hydrates and solvates of such salts.

9. The method of claim 1 , wherein the direct PPAR-gamma agonist is selected from the group consisting of:

5-[(2,4-dioxothiazolidin-5-yl)methyl]-2-methoxy-N-[[4-(trifluoromethyl)-phenyl]methyl]benzamide;

(+)-5-[[6-(2-fluorbenzyl)-oxy-2-naphy]methyl]-2,4-thiazolidinedione;

4-[4-[2-(5-methyl-2-phenyl-4-oxazolyl)ethoxy]benzyl]-3,5-isoxazolidinedione);

(−) 3 -[4-[2-(Phenoxazin-10-yl)ethoxy]phenyl]-2-ethoxypropanoic acid;

[5-[4-[2-(1-indolyl)ethoxy]phenyl]methyl]thiazolidine-2,4-dione;

5-[4-[2-(5 methyl-2-phenyl-4-oxazolyl)-2-hydroxyethoxy]benzyl]-2,4-thiazolidinedione;

(S)-2-ethoxy-3-[4-[2-(4-methylsulphonyloxyphenyl)ethoxy]phenyl]propanoic acid;

and {[±]-5-[(7-benzyloxy-3-quinolyl)methyl]-2,4-thiazolidinedione}.

10. The method of claim 1 , wherein the subject is a human.

11. The method of claim 1 , wherein the direct PPAR-gamma agonist is administered in an amount that is less than the usual therapeutic dose when administered alone.

12. The method of claim 1 , wherein the combined amount is selected so that the treatment results in one or more of weight loss and appetite reduction in the subject.

13. The method of claim 1 , wherein the direct PPAR-gamma agonist and the Compound of Formula I are mixed together to form an admixture and the admixture is administered to the subject.

14. The method of claim 1 , wherein the direct PPAR-gamma agonist and the Compound of Formula I are not mixed together to form an admixture but are administered independently to the subject.