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Combined use of a glp-1 compound and another drug for treating dyslipidemiaRelated Patent Categories: Drug, Bio-affecting And Body Treating Compositions, Designated Organic Active Ingredient Containing (doai), Peptide Containing (e.g., Protein, Peptones, Fibrinogen, Etc.) Doai, Cyclopeptides, 25 Or More Peptide Repeating Units In Known Peptide Chain StructureCombined use of a glp-1 compound and another drug for treating dyslipidemia description/claimsThe Patent Description & Claims data below is from USPTO Patent Application 20070207964, Combined use of a glp-1 compound and another drug for treating dyslipidemia. Brief Patent Description - Full Patent Description - Patent Application Claims
CROSS REFERENCE TO RELATED APPLICATIONS [0001] This application is a continuation of U.S. application Ser. No. 11/185,209, filed Jul. 20, 2005; which is a continuation of U.S. application Ser. No. 10/328,284 filed Dec. 23, 2002; and claims the benefit under 35 U.S.C. 119 of Danish applications PA 2001 01970 and PA 2002 00759 filed Dec. 29, 2001 and May 17, 2002 respectively, and of U.S. provisional application 60/350,088, filed Jan. 17, 2002, the contents of each of which are hereby incorporated by reference. FIELD OF THE INVENTION [0002] The present invention relates to methods for treatment and/or prevention of dyslipidemia. More specifically, the methods and uses of the invention pertains to administration of a GLP-1 compound in combination with administration of another antidyslipidemic agent. BACKGROUND OF THE INVENTION [0003] Diabetes is a disorder of carbohydrate metabolism characterized by hyperglycemia and glucosuria resulting from insufficient production or utilization of insulin. Diabetes severely affects the quality of life of large parts of the populations in developed countries. Insufficient production of insulin is characterized as type 1 diabetes and insufficient utilization of insulin is type 2 diabetes. [0004] Dyslipidemia, or abnormal levels of lipoproteins in serum, is a frequent occurrence among diabetics. In type 1 diabetes with optimal glycaemic control the concentrations of serum lipoproteins are typically characterized by normal to subnormal very low density lipoprotein (VLDL), elevated high density lipoprotein (HDL) cholesterol and normal to subnormal low density lipoprotein (LDL) cholesterol. Lipoprotein profile in type 1 diabetic patients with good glycaemic control is not atherogenic. In fact, it seems antiatherogenic although lack of lipoprotein abnormalities does not exclude the possibility that certain compositional alterations may be potentially atherogenic. In type 1 diabetics with poor glycaemic control the serum concentration of lipoproteins are typically characterized by increased VLDL, reduced HDL cholesterol and increased LDL cholesterol. This profile is atherogenic but it may be corrected by intensive insulin treatment of the patient to reach a state of good glycaemic control. [0005] In type 2 diabetes abnormalities of serum lipids and lipoproteins are much more frequent than in type 1 diabetes. Dyslipidemia in type 2 diabetes is typically characterized by elevated serum and VLDL triglycerides, low HDL cholesterol, normal to elevated levels of LDL cholesterol and increased levels of small dense, LDL particles in the blood. Serum and VLDL triglycerides are usually 1.5-3 times higher in type 2 diabetics as compared to non-diabetic controls with matched body mass index, age and sex. Regardless of the mode of treatment of type 2 diabetes, the characteristic lipoprotein profile is atherogenic. Furthermore, the excessive postprandial lipaemia is positively correlated with fasting serum triglyceride levels in type 2 diabetics. Taken together these abnormalities are significant risk factors not only for coronary heart disease but also for the progression of coronary artery disease. [0006] Dyslipidemia is one of the main contributors to the increased incidence of coronary events and deaths among diabetic subjects. Several epidemiological studies have confirmed this by showing a several-fold increase in coronary deaths among diabetic subjects when compared with non-diabetic subjects. Although the lipid profiles in type 1 diabetes and in type 2 diabetes both exhibit potentially atherogenic features, the lipoprotein profile in type 2 diabetes is atherogenic regardless of the mode of treatment. In type 2 diabetes the problem is of immense proportions since the majority of the patients have atherogenic dyslipidemia. In terms of atherogenic potential, dyslipidemia is comparable to hypercholesterolemia. Therefore, to relieve this burden accompanying diabetes new therapeutic approaches are needed. [0007] Several drugs are being used in the treatment of dyslipidemia. The drugs can intervene by lowering cholesterol (LDL and total cholesterol) or by lowering triglyceride levels in plasma. Treatment of hyperlipidemia using statins or PPAR/LXR modulating compounds such as fibric acid derivatives have been used to lower serum levels of cholesterol and triglyceride. Statins such as atorvastatin, lovastatin, fluvastatin, simvastatin and pravastatin are HMG CoA reductase inhibitors which act by inhibiting cholesterol synthesis and upregulate LDL receptors in liver. Statins are used to treat elevated LDL, and common side effects are myositis, arthralgias, gastrointestinal upset and elevated liver function tests. The fibric acid derivatives, e.g. clofibrate, gemfibrozil, fenofibrate and ciprofibrate, stimulate lipoprotein lipase that breaks down lipids in lipoproteins and may decrease VLDL synthesis. Fibric acid derivatives are used to treat elevated triglyceride levels and among the side effects are myositis, gastrointestinal upset, gallstones and elevated liver function tests. Other drug types used for treatment of hyperlipidemia are bile acid binding resins (bile acid sequestrants), e.g. cholestyramine and cholestipol, with the major indication being elevated LDL. Bile acid binding resins promote bile acid excretion and they increase LDL receptors in the liver. Common side effects are bloating, constipation and elevated triglycerides. Nicotinic acid decreases VLDL synthesis and is used for treatment of elevated LDL and VLDL. Among the side effects of nicotinic acid are cutaneous flushing, gastrointestinal upset, elevated glucose, uric acid and liver function tests. Thus, there is a need for the therapeutic benefits of several antidyslipidemic drugs while simultaneously reducing the severe side effects. [0008] Human GLP-1 is a 37 amino acid residue peptide originating from preproglucagon which is synthesized i.a. in the L-cells in the distal ileum, in the pancreas and in the brain. GLP-1 is an important gut hormone with regulatory function in glucose metabolism and gastrointestinal secretion and metabolism. Processing of preproglucagon to give GLP-1(7-36)amide, GLP-1(7-37) and GLP-2 occurs mainly in the L-cells. A simple system is used to describe fragments and analogues of this peptide. Thus, for example, Gly.sup.8-GLP-1(7-37) designates a fragment of GLP-1 formally derived from GLP-1 by deleting the amino acid residues Nos. 1 to 6 and substituting the naturally occurring amino acid residue in position 8 (Ala) by Gly. Similarly, Lys.sup.34(N.sup..epsilon.-tetradecanoyl)-GLP-1(7-37) designates GLP-1(7-37) wherein the .epsilon.-amino group of the Lys residue in position 34 has been tetradecanoylated. PCT publications WO 98/08871 and WO 99/43706 disclose derivatives of GLP-1 analogs, which have a lipophilic substituent. These stable derivatives of GLP-1 analogs have a protracted profile of action compared to the corresponding GLP-1 analogs. In addition to a number of other desirable effects, GLP-1 compounds have also been shown to lower plasma levels of triglycerides and cholesterol (WO 2001/66135). A number of structural analogs of GLP-1 were isolated from the venom of the Gila monster lizards (Heloderma suspectum and Heloderma hortidum). Exendin-4 is a 39 amino acid residue peptide isolated from the venom of Heloderma horridum, and this peptide shares 52% homology with GLP-1. Exendin-4 is a potent GLP-1 receptor agonist which has been shown to stimulate insulin release and ensuing lowering of the blood glucose level when injected into dogs. Exendin-4, exendin-4 analogs and derivatives of any of these as well as methods for production thereof can be found in WO 99/43708, WO 00/66629, and WO 01/04156. The group of GLP-1(1-37), exendin-4(1-39), analogs thereof and derivatives thereof, (hereinafter designated GLP-1 compounds) are potent insulinotropic agents. SUMMARY OF THE INVENTION [0009] The present invention relates to the use of a GLP-1 compound in combination with another antidyslipidemic drug to treat dyslipidemia in diabetics and non-diabetics. This combined treatment conveys the benefits of both compounds while reducing side effects associated with each compound. [0010] In accordance with the present invention, a pharmaceutical combination is provided for use in treatment of dyslipidemia in diabetics and in non-diabetics, which combination comprises a GLP-1 compound and another antidyslipidemic drug. [0011] One object of the present invention is to provide methods, which can effectively be used in the treatment or prophylaxis of dyslipidemia, hyperlipoproteinemia, hypertriglyceridemia, hyperlipidemia or hypercholesterolemia. [0012] The invention includes a method for the treatment or prophylaxis of dyslipidemia, hyperlipoproteinemia, hypertriglyceridemia, hyperlipidemia or hypercholesterolemia, which method comprises administration of a GLP-1 compound and an antidyslipidemic drug to a patient in need thereof. [0013] In one embodiment of the invention, the GLP-1 compound is a stable derivative of a GLP-1 analog. A preferred embodiment is a GLP-1 analog with a lipophilic substituent, preferably Arg.sup.34, Lys.sup.26(N.sup..epsilon.-(.gamma.-Glu(N.sup..alpha.-hexadecanoyl)))-GLP- -1(7-37). [0014] In other embodiments of the invention the antidyslipidemic drug is a statin, a squalene synthase inhibitor, a bile acid binding resin or an IBAT inhibitor. [0015] In yet another embodiment of the invention the antidyslipidemic drug and the GLP-1 compound are administered in suboptimal dosages. In yet another embodiment of the invention the antidyslipidemic drug and the GLP-1 compound are administered in amounts and for a sufficient time to produce a synergistic effect. DEFINITIONS [0016] Co-administration: In the context of the present application, co-administration of two compounds is defined as administration of the two compounds to the patient within 24 hours, including separate administration of two medicaments each containing one of the compounds as well as simultaneous administration whether or not the two compounds are combined in one formulation or whether they are in two separate formulations. [0017] Effective dosage: An effective dosage is a dosage which is sufficient in order for the treatment of the patient to be effective. [0018] GLP-1 compound: A GLP-1 analog or a derivative thereof or exendin-4, an exendin-4 analog or a derivative thereof. For example, Gly.sup.8-GLP-1(7-37) designates a fragment of GLP-1 formally derived from GLP-1 by deleting the amino acid residues Nos. 1 to 6 and substituting the naturally occurring amino acid residue in position 8 (Ala) by Gly. Examples of derivatives of GLP-1 analogs can be found in WO 98/08871 and WO 99/43706. Likewise, exendin-4 and analogs and derivatives thereof are described in WO 99/43708, WO 00/66629 and WO 01/04146. [0019] In the present application an analog of a parent protein means a protein wherein one or more amino acid residues of the parent protein have been substituted by other amino acid residues and/or wherein one or more amino acid residues of the parent protein have been deleted and/or wherein one or more amino acid residues have been inserted into the parent protein. Such an insertion of amino acid residues can take place at the C-terminal, at the N-terminal, within the peptide sequence or a combination thereof. In the present application the term "derivative" means a chemical derivative of the parent protein, i.e. a protein wherein at least one of the constituent amino acid residues are covalently modified. Examples of such covalent modifications are acylations, alkylations, esterifications, glycosylations and PEGylations. Continue reading about Combined use of a glp-1 compound and another drug for treating dyslipidemia... Full patent description for Combined use of a glp-1 compound and another drug for treating dyslipidemia Brief Patent Description - Full Patent Description - Patent Application Claims Click on the above for other options relating to this Combined use of a glp-1 compound and another drug for treating dyslipidemia patent application. ###  How KEYWORD MONITOR works... a FREE service from FreshPatents1. Sign up (takes 30 seconds). 2. Fill in the keywords to be monitored. 3. Each week you receive an email with patent applications related to your keywords. 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