Method of treating the syndrome of coronary heart disease risk factors in humans

1. A method for treating one or more conditions of metabolic syndrome of Coronary Heart Disease Risk Factors (CHDRF) comprising at least one of Insulin Resistance, BetaCell Dysfunction, Impaired Glucose Tolerance, Type 2 Diabetes, overweightness, obesity and dyslipidemia in a patient suffering therefrom, the method comprising administering to said patient, by a pharmaceutically effective mode, a drug composition comprising:

an opioidergic agent; and

an insulin secretagogue.

2. The method of claim 1 , wherein the opioidergic agent is an opiate antagonist, an opiate having μ-agonist activity or a combination thereof.

3. The method of claim 2 , wherein the opiate antagonist comprises a single molecular entity.

4. The method of claim 2 , wherein the opiate antagonist comprises a combination of molecular entities.

5. The method of claim 2 , wherein the opiate having μ-agonist activity comprises a single molecular entity.

6. The method of claim 2 , wherein the opiate having μ-agonist activity comprises a combination of molecular entities.

7. The method of claim 2 , wherein the drug composition comprises a peripherally acting μ-agonist.

8. The method of claim 7 , wherein the drug composition comprises loperamide.

9. The method of claim 2 , wherein the drug composition comprises a centrally acting μ-agonist.

10. The method of claim 2 , wherein the drug composition further comprises an opiate having mixed μ-agonist and κ antagonist activity.

11. The method of claim 10 , wherein the opiate having mixed μ-agonist and κ antagonist activity is buprenorphine.

12. The method of claim 2 wherein the opioidergic agent includes at least one of the following:

i) dihydromorphine;

ii) morphine;

iii) hydromorphone;

iv) methadone;

v) fentanyl;

vi) sufentanyl;

vii) buprenorphine;

viii) demorphine;

ix) codeine;

x) ethylmorphine;

xi) etonitazene;

xii) hydrocodone;

xiii) levorphanol;

xiv) norcodeine;

xv) normophine;

xvi) (D-Ala 2 -N-Me-Phe 4 -Gly 3 -ol)-Enkephalin (DAMGO); and

xvii) oxycodone.

13. The method of claim 2 , wherein the opioidergic agent includes at least one of the following:

i) nalmefene;

ii) naltrexone;

iii) nor-binaltorphimine;

iv) (−)-(1R,5R,9R)-5,9-diethyl-2-(3-furylmethyl)-2-hydroxy-6,7-benzomorphan (MR 2266);

v) a triethylenedioxy derivative of B-naltrexamine (TENA); and

vi) guanidylated naltrindole (GNTI).

14. The method of claim 2 , wherein the condition included within the CHDRF Syndrome is Insulin Resistance (IR).

15. The method of claim 2 , wherein the condition included within the CHDRF Syndrome is Beta-Cell Dysfunction.

16. The method of claim 2 , wherein the condition included within the CHDRF Syndrome is Impaired Glucose Tolerance (IGT).

17. The method of claim 2 , wherein the condition included within the CHDRF Syndrome is Type 2 Diabetes.

18. The method of claim 2 , wherein the condition included within the CHDRF syndrome is overweight.

19. The method of claim 2 , wherein the condition included within the CHDRF syndrome is obesity.

20. The method of claim 2 , wherein the condition included within the CHDRF syndrome is dyslipidemia.

21. The method of claim 1 , wherein the insulin secretagogue includes at least one of the following:

i. sulphonylureas;

ii. tolbutamide;

iii. chlorpropamide;

iv. glimepiride;

v. glipizide;

vi. glyburide;

vii. meglitinides;

viii. repaglinide;

ix. pramlintide;

x. morphilinoguanide;

xi. acetylcholine;

xii. muscannic agonists;

xiii. carbachol;

xiv. bethanechol;

xv. beta-L-glucose pentaacetate;

xvi. chiro-inositol;

xvii. myo-inositol;

xviii. GIP;

xix. GLP-1; and

xx. Extendin-4.

22. The method of claim 1 , wherein the insulin secretagogue is a non-glucose dependent insulin secretagogue, the method producing insulin release patterns capable of attaining glucose dependent, bi-phasic release characteristics with reduced likelihood of producing hypoglycemia.

23. The method of claim 22 , wherein the insulin secretagogue is sulphonylurea.

24. A method for treating one or more conditions of metabolic syndrome of Coronary Heart Disease Risk Factors (CHDRF) comprising at least one of Insulin Resistance, BetaCell Dysfunction, Impaired Glucose Tolerance, Type 2 Diabetes, overweightness, obesity and dyslipidemia in a patient suffering therefrom, the method comprising administering to said patient, by a pharmaceutically effective mode, a drug composition comprising:

an opiate antagonist; and

an insulin secretagogue.

25. The method of claim 24 , wherein the opiate antagonist comprises a single molecular entity.

26. The method of claim 24 , wherein the opiate antagonist comprises a combination of molecular entities.

27. The method of claim 24 , wherein the opiate antagonist includes at least one of the following:

i) nalmefene

ii) naltrexone;

iii) nor-binaltorphimine;

iv) (−)-(1R,5R,9R)-5,9-diethyl-2-(3-furylmethyl)-2-hydroxy-6,7-benzomorphan (MR 2266);

v) a triethylenedioxy derivative of B-naltrexamine (TENA); and

vi) guanidylated naltrindole (GNTI).

28. The method of claim 24 , wherein the condition included within the CHDRF Syndrome is Insulin Resistance.

29. The method of claim 24 , wherein the condition included within the CHDRF Syndrome is Beta-Cell Dysfunction.

30. The method of claim 24 , wherein the condition included within the CHDRF syndrome is Impaired Glucose Tolerance (IGT).

31. The method of claim 24 , wherein the condition included within the CHDRF syndrome is Type 2 Diabetes.

32. The method of claim 24 , wherein the condition included within the CHDRF syndrome is overweight.

33. The method of claim 24 , wherein the condition included within the CHDRF syndrome is obesity.

34. The method of claim 24 , wherein the condition included within the CHDRF syndrome is dyslipidemia.

35. The method of claim 24 wherein the opiate antagonist has IC 50 levels for the μ, δ, and κ opiate receptors, the IC 50 levels being {(IC 50 κ/IC 50 μ)<3} and {(IC 50 κ/IC 50 δ)<3}.

36. The method of claim 24 , wherein the insulin secretagogue includes at least one of the following:

i. sulphonylureas;

ii. tolbutamide;

iii. chlorpropamide;

iv. glimepiride;

v. glipizide;

vi. glyburide;

vii. meglitinides;

viii. repaglinide;

ix. pramlintide;

x. morphilinoguanide;

xi. acetylcholine;

xii. muscannic agonists;

xiii. carbachol;

xiv. bethanechol;

xv. beta-L-glucose pentaacetate;

xvi. chiro-inositol;

xvii. myo-inositol;

xviii. GIP;

xix. GLP-1; and

xx. Extendin-4.

37. The method of claims 24 , wherein the insulin secretagogue is a non-glucose dependent insulin secretagogue, the method producing insulin release patterns capable of attaining glucose dependent, bi-phasic release characteristics with reduced likelihood of producing hypoglycemia.

38. The method of claim 37 , wherein the insulin secretagogue is sulphonylurea.

39. A method for treating one or more conditions of metabolic syndrome of Coronary Heart Disease Risk Factors (CHDRF) comprising at least one of Insulin Resistance, BetaCell Dysfunction, Impaired Glucose Tolerance, Type 2 Diabetes, overweightness, obesity and dyslipidemia in a patient suffering therefrom, the method comprising administering to said patient, by a pharmaceutically effective mode, a drug composition comprising:

an opiate agonist; and

an insulin secretagogue.

40. The method of claim 39 , wherein the opiate agonist comprises a single molecular entity.

41. The method of claim 39 , wherein the opiate agonist comprises a combination of molecular entities.

42. The method of claim 39 , wherein the opiate agonist is a peripherally acting μ-agonist.

43. The method of claim 42 , wherein the opiate agonist is loperamide.

44. The method of claim 39 , wherein the opiate agonist is a centrally acting μagonist.

45. The method of claim 39 , wherein the opiate agonist includes at least one of the following:

i) dihydromorphine;

ii) morphine;

iii) hydromorphone;

iv) methadone;

v) fentanyl;

vi) sufentanyl;

vii) demorphine;

viii) codeine;

ix) ethylmorphine;

x) etonitazene;

xi) hydrocodone;

xii) levorphanol;

xiii) norcodeine;

xiv) normophine;

xv) (D-Ala 2 -N-Me-Phe 4 -Gly 3 -ol)-Enkephalin (DAMGO); and

xvi) oxycodone.

46. The method of claim 39 , wherein the condition included within the CHDRF Syndrome is Insulin Resistance.

47. The method of claim 39 , wherein the condition included within the CHDRF Syndrome is Beta-Cell Dysfunction.

48. The method of claim 39 , wherein the condition included within the CHDRF syndrome is Impaired Glucose Tolerance (IGT).

49. The method of claim 39 , wherein the condition included within the CHDRF syndrome is Type 2 Diabetes.

50. The method of claim 39 , wherein the condition included within the CHDRF syndrome is overweight.

51. The method of claim 39 , wherein the condition included within the CHDRF syndrome is obesity.

52. The method of claim 39 , wherein the condition included within the CHDRF syndrome is dyslipidemia.

53. The method of claim 39 , wherein the insulin secretagogue includes at least one of the following:

i. suipnonylureas;

ii. tolbutamide;

iii. chlorpropamide;

iv. glimepiride;

v. glipizide;

vi. glyburide;

vii. meglitinides;

viii. repaglinide;

ix. pramlintide;

x. morphilinoguanide;

xi. acetylcholine;

xii. muscarimc agonists;

xiii. carbachol;

xiv. bethanechol;

xv. beta-L-glucose pentaacetate;

xvi. chiro-inositol;

xvii. myo-inositol;

xviii. GIP;

xix. GLP-1; and

xx. Extendin-4.

54. The method of claims 39 , wherein the insulin secretagogue is a non-glucose dependent insulin secretagogue, the method producing insulin release patterns capable of attaining glucose dependent, bi-phasic release characteristics with reduced likelihood of producing hypoglycemia.

55. The method of claim 39 , wherein the insulin secretagogue is sulphonylurea.

56. The method of claim 2 , wherein opiate agonist comprises tramadol.

57. The method of claim 2 , wherein the drug composition comprises at least one of CHMMO, diprenorphine, and a combination thereof.

58. The method of claim 2 , wherein the opiate antagonist has IC 50 levels for the μ, δ, and κ opiate receptors, the IC 50 levels being {(IC 50 κ/IC 50 μ)<3} and {(IC 50 κ/IC 50 δ)<3}.

59. The method of claim 2 , wherein the opiate antagonist has IC 50 levels for the μ, δ, and κ opiate receptors, the IC 50 levels being {(IC 50 κ/IC 50 μ)<10} and {(IC 50 κ/IC 50 δ)<10}.

60. The method of claim 1 , wherein the drug composition is administered in a daily dose comprising less than about 10 μg/kg opioidergic agent and equal to or less than about 10 μg/kg of insulin secretagogue for monotherapy.

61. The method of claim 39 , wherein opiate agonist comprises tramadol.

62. The method of claim 24 , wherein the drug composition comprises at least one of CHMMO, diprenorphine, and a combination thereof.

63. The method of claim 24 , wherein the opiate antagonist has IC 50 levels for the μ, δ, and κ opiate receptors, the IC 50 levels being {(IC 50 κ/IC 50 μ)<10} and {(IC 50 κ/IC 50 δ)<10}.