Therapies for Obesity, Diabetes and Related Indications

Abstract

The invention relates to methods, uses, compositions and formulations including a melanocortin receptor-4 agonist and a glucagon-like peptide-1 receptor agonist for treatment of obesity, diabetes, metabolic syndrome and related indications, diseases or disorders.

We claim: 
     
         1 . A method of decreasing side effects associated with therapeutic agents for treatment of obesity, diabetes or metabolic syndrome in a patient, comprising:
 administration of a quantity of melanocortin receptor-4 agonist, wherein the quantity of melanocortin receptor-4 agonist administered, if administered as a monotherapy not in conjunction with glucagon-like peptide-1 receptor agonist, is not sufficient to initiate the desired pharmacological response in treating at least one condition from the group comprising obesity, diabetes and metabolic syndrome in the patient when administered as a monotherapy; and   administration of a quantity of glucagon-like peptide-1 receptor agonist, wherein the quantity of glucagon-like peptide-1 receptor agonist administered, if administered as a monotherapy not in conjunction with melanocortin receptor-4 agonist, is not sufficient to initiate the desired pharmacological response in treating at least one condition from the group comprising obesity, diabetes and metabolic syndrome in the patient when administered as a monotherapy;   wherein the quantity of the melanocortin receptor-4 agonist and the quantity of glucagon-like peptide-1 receptor agonist are together effective to initiate the desired pharmacological response treating at least one condition from the group comprising obesity, diabetes and metabolic syndrome in the patient,   thereby reducing side effects in the treatment of at least one of obesity, diabetes or metabolic syndrome in the patient.   
     
     
         2 . The method of  claim 1  wherein the quantity of melanocortin receptor-4 agonist administered is not sufficient to initiate the desired pharmacological response of inducing weight loss. 
     
     
         3 . The method of  claim 1  or  2  wherein the quantity of melanocortin receptor-4 agonist administered is sufficient to induce minimal weight loss. 
     
     
         4 . The method of  claim 1  wherein the desired pharmacological response is inducing weight loss. 
     
     
         5 . The method of  claim 1  wherein the desired pharmacological response is inducing glycemic control. 
     
     
         6 . A method of treating obesity or inducing weight loss in an obese patient, comprising the steps of:
 establishing a dose of a glucagon-like peptide-1 receptor agonist which induces glycemic control in the patient but which induces no more than minimal weight loss in the patient;   administration of the dose of the glucagon-like peptide-1 receptor agonist; and   administration of a melanocortin receptor-4 agonist;   wherein the dose of the glucagon-like peptide-1 receptor agonist and the quantity of melanocortin receptor-4 agonist are effective to treat obesity or to induce weight loss.   
     
     
         7 . The method of  claim 6  wherein the dose of glucagon-like peptide-1 receptor agonist does not induce minimal weight loss in the patient. 
     
     
         8 . The method of  claim 6  wherein the administration of the dose of the glucagon-like peptide-1 receptor agonist and administration of a melanocortin receptor-4 agonist are simultaneous. 
     
     
         9 . The method of  claim 8  wherein the simultaneous administration is by means of a combination pharmaceutical composition comprising glucagon-like peptide-1 receptor agonist and melanocortin receptor-4 agonist. 
     
     
         10 . The method of  claim 6  wherein the melanocortin receptor-4 agonist is Ac-Arg-cyclo(Orn-Asn-D-Phe-Arg-Trp-Glu)-NH 2  administered daily. 
     
     
         11 . The method of  claim 6  wherein Ac-Arg-cyclo(Orn-Asn-D-Phe-Arg-Trp-Glu)-NH 2  is administered by subcutaneous injection. 
     
     
         12 . The method of  claim 6  wherein the glucagon-like peptide-1 receptor agonist is administered by subcutaneous injection. 
     
     
         13 . The method of  claim 12  wherein the glucagon-like peptide-1 receptor agonist is liraglutide or exenatide administered daily or twice daily. 
     
     
         14 . The method of  claim 12  wherein the glucagon-like peptide-1 receptor agonist is lixisenatide, albiglutide, dulaglutide or an extended release formulation of exenatide or liraglutide administered at weekly or greater intervals. 
     
     
         15 . The method of  claim 6  wherein administration of the dose of the glucagon-like peptide-1 receptor agonist and administration of a melanocortin receptor-4 agonist elicits a synergistic effect on treatment of obesity. 
     
     
         16 . The method of  claim 6  wherein administration of the dose of the glucagon-like peptide-1 receptor agonist and administration of a melanocortin receptor-4 agonist elicits a synergistic effect on inducing glycemic control.