Lowering Serum Lipids
The present invention relates to a method for lowering serum lipids, eg. triglycerides and/or cholesterol in a subject comprising administering a GLP-1 agonist to said subject.
1 . A method for lowering levels of one or more serum lipids in a patient, said method comprising administering to a patient in need thereof a lipid-lowering effective amount of a GLP-1 agonist.
2 . A method according to claim 1 , wherein said one or more serum lipids are selected from the group consisting of: low density lipoprotein (LDL); small, dense LDL; very low density lipoprotein (VLDL); triglycerides; free fatty acids; cholesterol; and high-density lipoprotein (HDL).
3 . A method according to claim 1 , wherein said GLP-1 agonist is selected from the group consisting of Arg 26 , Lys 34 (N-ε-(γ-Glu(N-α-hexadecanoyl)))-GLP-1(7-37), Arg 34 , Lys 26 (N-ε-(γ-Glu(N-α-hexadecanoyl)))-GLP-1(7-37), exendin-3, exendin-4, Val 8 -GLP-1(7-37), Thr 8 -GLP-1(7-37), Met 8 - GLP-1(7-37), and Gly 8 -GLP-1(7-37).
4 . A method according to claim 1 , wherein said GLP-1 agonist binds to a GLP-1 receptor with an affinity constant (Kd) below 1 μM.
5 . A method according to claim 1 , further comprising administering to said patient a compound selected from the group consisting of growth hormone, a growth hormone releasing agent, prolactin, and placental lactogen, under conditions effective for said reduction.
6 . A method according to claim 1 , further comprising administering to said patient a non-GLI-1 agonist antihyperlipidemic agent.
7 . A method according to claim 6 , wherein said antihyperlipidemic agent is selected from the group consisting of cholestyramine, colestipol, clofibrate, gemfibrozil, lovastatin, pravastatin, simvastatin, probucol, and dextrothyroxine.
8 . A method according to claim 1 , further comprising administering to said patient an antihypertensive-effective amount of an antihypertensive agent selected from the group consisting of β-blockers, calcium channel blockers, and α-blockers.
9 . A method according to claim 1 , further comprising administering to said patient an appetite-regulating effective amount of an appetite-regulating agent selected from the group consisting of CART (cocaine amphetamine regulated transcript) agonists, NPY (neuropeptide Y) antagonists, MC4 (melanocortin 4) agonists, orexin antagonists, TNF (tumor necrosis factor) agonists, CRF (corticotropin releasing factor) agonists, CRF BP (corticotropin releasing factor binding protein) antagonists, urocortin agonists, β3 agonists, MSH (melanocyte-stimulating hormone) agonists, MCH (melanocyte-concentrating hormone) antagonists, CCK (cholecystokinin) agonists, serotonin re-uptake inhibitors, serotonin and noradrenaline re-uptake inhibitors, 5HT (serotonin) agonists, bombesin agonists, galanin antagonists, TRH (thyrotropin releasing hormone) agonists, UCP 2 or 3 (uncoupling protein 2 or 3) modulators, leptin agonists, DA (dopamine) agonists (bromocriptin, doprexin), lipase/amylase inhibitors, PPAR modulators, RXR modulators, and TR β agonists.
10 . A method according to claim 1 , further comprising administering to said patient an antidiabetic-effective amount of an antidiabetic agent selected from the group consisting of insulin, a sulfonylurea, a biguanide, a thiazolidinedione, an α-glucosidase inhibitor, and an insulin sensitizer.
11 . A method according to claim 1 , wherein said patient suffers from a disease state that is alleviated by lowering serum levels of said one or more lipids.
12 . A method for lowering levels of free fatty acids in a patient, said method comprising administering to a patient in need thereof an amount of a GLP-1 agonist effective to lower said free fatty acid levels.
13 . A method according to claim 12 , wherein said GLP-1 agonist is selected from the group consisting of Arg 26 , Lys 34 (N-ε-(γ-Glu(N-α-hexadecanoyl)))-GLP-1(7-37), Arg 34 , Lys 26 (N-ε-(γ-Glu(N-α-hexadecanoyl)))-GLP-1(7-37), exendin-3, exendin-4, Val 8 -GLP-1(7-37), Thr 8 - GLP-1(7-37), Met 8 - GLP-1(7-37), and Gly 8 -GLP-1(7-37).
14 . A method according to claim 14 , wherein said GLP-1 agonist binds to a GLP-1 receptor with an affinity constant (Kd) below 1 μM.
15 . A method for reducing the serum level of lipoprotein A (lp(A)) and/or apolipoprotein A (apo(A)) in a patient in need of such treatment, said method comprising administering to said patient a GLP-1 agonist in an amount effective for said reduction.
16 . A method according to claim 15 , wherein said GLP-1 agonist is selected from the group consisting of Arg 26 , Lys 34 (N-ε-(γ-Glu(N-α-hexadecanoyl)))-GLP-1(7-37), Arg 34 , Lys 26 (N-ε-(γ-Glu(N-α-hexadecanoyl)))-GLP-1(7-37), exendin-3, exendin-4, Val 8 -GLP-1(7-37), Thr 8 - GLP-1(7-37), Met 8 - GLP-1(7-37), and Gly 8 -GLP-1(7-37).
17 . A method according to claim 15 , wherein said GLP-1 agonist binds to a GLP-1 receptor with an affinity constant (Kd) below 1 μM.
18 . A method for lowering levels of triglycerides in a patient, said method comprising administering to a patient in need thereof an amount of a GLP-1 agonist effective to lower said triglyceride levels.
19 . The method according to claim 18 , wherein said GLP-1 agonist is selected from the group consisting of Arg 26 , Lys 34 (N-ε-(γ-Glu(N-α-hexadecanoyl)))-GLP-1(7-37), Arg 34 , Lys 26 (N-ε-(γ-Glu(N-α-hexadecanoyl)))-GLP-1(7-37), exendin-3, exendin-4, Val 8 -GLP-1(7-37), Thr 8 - GLP-1(7-37), Met 8 - GLP-1(7-37), and Gly 8 -GLP-1(7-37).
20 . The method according to claim 18 , wherein said GLP-1 agonist binds to a GLP-1 receptor with an affinity constant (Kd) below 1 μM.