Therapeutic Regimens and Methods for Reducing Body Weight and/or Serum Lipids using a GLP-1R and GCGR Agonist

1 . A method for treatment of chronic weight management in a human being in need thereof comprising, administering to the human being a once weekly therapeutically effective amount of a pharmaceutical dosage formulation comprising at least 1.2 mg and up to 2.4 mg of a peptide product according to SEQ ID NO: 1, or a peptide product that is at least 80% identical to a peptide of SEQ ID NO: 1, and wherein the human being in need thereof has a co-morbidity selected from one or more of cardiovascular disease, hypertension, dyslipidemia, dysglycemia, and obstructive sleep apnea.

2 . The method of claim 1 , wherein the treatment further reduces serum lipids.

3 . A method for treatment of chronic weight management in a human being in need thereof comprising, administering to the human being a once weekly therapeutically effective amount of a pharmaceutical dosage formulation comprising at least 1.2 mg and up to 2.4 mg of a peptide product according to SEQ ID NO: 1, or peptide product that is at least 80% identical to a peptide of SEQ ID NO: 1, and wherein the treatment further reduces serum lipids.

4 . The method of claim 3 , wherein the human being in need thereof has a co-morbidity selected from one or more of cardiovascular disease, hypertension, dyslipidemia, dysglycemia, and obstructive sleep apnea.

5 . The method of any preceding claim , wherein the peptide product is at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98% or at least 99% identical to a peptide of SEQ ID NO: 1.

6 . The method of any preceding claim , wherein the peptide product is 100% identical to a peptide of SEQ ID NO: 1.

7 . The method of any preceding claim , wherein the pharmaceutical dosage formulation is administered subcutaneously or by parenteral injection.

8 . The method of any preceding claim , wherein the pharmaceutical dosage is an aqueous formulation comprising one or more of polysorbate 20, arginine, or mannitol.

9 . The method of any preceding claim , wherein the pharmaceutical dosage formulation comprises about 0.025-0.5% (w/w) polysorbate 20, about 0.2-0.5% (w/w) arginine, and about 3-6% (w/w) mannitol in water (pH 7.7±0.1).

10 . The method of any preceding claim , wherein the pharmaceutical dosage formulation comprises about 0.2% (w/w) polysorbate 20, about 0.348% (w/w) arginine, about 4.260% (w/w) mannitol in water (pH 7.7±0.1).

11 . The method of any preceding claim , wherein the human being is obese or overweight.

12 . The method of any preceding claim , wherein the human being in need thereof has a body mass index (BMI kg/m 2 ) of at least 25.

13 . The method of any preceding claim , wherein the human being in need thereof has a body mass index (BMI kg/m 2 ) of at least 30.

14 . The method of any preceding claim , wherein the human being in need thereof has a body mass index (BMI kg/m 2 ) of at least 35.

15 . The method of any preceding claim , wherein the human being in need thereof has a body mass index (BMI kg/m 2 ) of at least 40.

16 . The method of any preceding claim , wherein the treatment maintains weight loss.

17 . The method of any preceding claim , wherein the treatment reduces relative body weight by at least about 10%, by at least about 15% or by at least about 20%.

18 . The method of any preceding claim , wherein the treatment reduces lean body mass by less than about 25%.

19 . The method of any preceding claim , wherein the human being in need thereof has an HbA1C value of about 5.7% to 6.4%.

20 . The method of claim 1-14 , wherein the human being in need thereof has an HbA1C value of about 4.0% to 5.6%.

21 . The method of any preceding claim , wherein the pharmaceutical dosage formulation comprises about 1.2 mg of the peptide product.

22 . The method of any preceding claim , wherein the pharmaceutical dosage formulation comprises about 1.8 mg of the peptide product.

23 . The method of any preceding claim , wherein the pharmaceutical dosage formulation comprises about 2.4 mg of the peptide product.

24 . The method of any preceding claim , wherein the pharmaceutical dosage formulation comprises (2.4 mg/ml; 0.24% (w/w)) of the peptide product; Mannitol (42.6 mg/mL; 4.26% (w/w)); Arginine (3.48 mg/mL; 0.348% (w/w)); and polysorbate 20 (2 mg/mL; 0.2% (w/w)) in sterile water.

25 . The method of any preceding claim , wherein the pharmaceutical dosage formulation comprises (1.8 mg/ml; 0.18% (w/w)) of the peptide product; Mannitol (42.6 mg/mL; 4.26% (w/w)); Arginine (3.48 mg/mL; 0.348% (w/w)); and polysorbate 20 (2 mg/mL; 0.2% (w/w)) in sterile water.

26 . The method of any preceding claim , wherein the pharmaceutical dosage formulation comprises (1.2 mg/ml; 0.12% (w/w)) of the peptide product; Mannitol (42.6 mg/mL; 4.26% (w/w)); Arginine (3.48 mg/mL; 0.348% (w/w)); and polysorbate 20 (2 mg/mL; 0.2% (w/w)) in sterile water.

27 . The method of any preceding claim , wherein the treatment reduces one or more serum lipids selected from serum triglycerides, total serum cholesterol, serum LDL, or serum VLDL.

28 . The method of any preceding claim , wherein the treatment reduces serum triglycerides by at least about 30% after 48 weeks.

29 . The method of any preceding claim , wherein the treatment reduces total serum cholesterol by at least about 10% after 48 weeks.

30 . The method of any preceding claim , wherein the treatment reduces total serum cholesterol by at least about 15% after 48 weeks.

31 . The method of any preceding claim , wherein the treatment reduces serum LDL by at least about 10% after 48 weeks.

32 . The method of any preceding claim , wherein the treatment reduces serum VLDL by at least about 25% after 48 weeks.

33 . The method of any preceding claim , wherein the treatment reduces serum triglycerides by at least about 30% after 48 weeks in human being in need thereof with >150 mg/dL triglycerides at baseline.

34 . The method of any preceding claim , wherein the treatment reduces serum triglycerides by at least about 50% after 48 weeks in human being in need thereof with >150 mg/dL triglycerides at baseline.

35 . The method of any preceding claim , wherein the treatment reduces serum cholesterol by at least about 15% after 48 weeks in human being in need thereof with >200 mg/dL cholesterol at baseline.

36 . The method of any preceding claim , wherein the treatment reduces serum cholesterol by at least about 20% after 48 weeks in human being in need thereof with >200 mg/dL cholesterol at baseline.

37 . The method of any preceding claim , wherein the treatment reduces serum LDL by at least about 15% after 48 weeks in human being in need thereof with >130 mg/dL LDL at baseline.

38 . The method of any preceding claim , wherein the treatment reduces serum LDL by at least about 20% after 48 weeks in human being in need thereof with >130 mg/dL LDL at baseline.

39 . The method of any preceding claim , wherein a steady state therapeutic dose is achieved after a dose escalating phase having a duration of from two to four weeks.

40 . A method for treatment of reducing serum lipids in a human being in need thereof, comprising administering to the human being a once weekly therapeutically effective amount of a pharmaceutical dosage formulation comprising at least 1.2 mg and up to 2.4 mg of a peptide product according to SEQ ID NO: 1, or peptide product that is at least 80% identical to a peptide of SEQ ID NO: 1.

41 . The method of claim 40 , wherein the human being in need thereof has a co-morbidity selected from one or more of obesity, cardiovascular disease, hypertension, dyslipidemia, dysglycemia, type 2 diabetes and obstructive sleep apnea.

42 . The method of claim 40 or 41 , wherein the peptide product is at least 85%, at least 90%, at least 95%, at least 96%, at least 97%, at least 98% or at least 99% identical to a peptide of SEQ ID NO: 1.

43 . The method of claim 40 or 41 , wherein the peptide product is 100% identical to a peptide of SEQ ID NO: 1.

44 . The method of claim 40-43 , wherein the pharmaceutical dosage formulation is administered subcutaneously or by parenteral injection.

45 . The method of claim 40-44 , wherein the pharmaceutical dosage is an aqueous formulation comprising one or more of polysorbate 20, arginine, or mannitol.

46 . The method of any claim 40-45 , wherein the pharmaceutical dosage formulation comprises about 0.025-0.5% (w/w) polysorbate 20, about 0.2-0.5% (w/w) arginine, and about 3-6% (w/w) mannitol in water (pH 7.7±0.1).

47 . The method of any claim 40-46 , wherein the pharmaceutical dosage formulation comprises about 0.2% (w/w) polysorbate 20, about 0.348% (w/w) arginine, about 4.260% (w/w) mannitol in water (pH 7.7±0.1).

48 . The method of any claim 40-47 , wherein the human being is obese or overweight.

49 . The method of any claim 40-48 , wherein the human being in need thereof has a body mass index (BMI kg/m 2 ) of at least 25.

50 . The method of any claim 40-49 , wherein the human being in need thereof has a body mass index (BMI kg/m 2 ) of at least 30.

51 . The method of any claim 40-50 , wherein the human being in need thereof has a body mass index (BMI kg/m 2 ) of at least 35.

52 . The method of any claim 40-51 , wherein the human being in need thereof has a body mass index (BMI kg/m 2 ) of at least 40.

53 . The method of any claim 40-52 , wherein the treatment maintains weight loss.

54 . The method of any claim 40-53 , wherein the treatment reduces relative body weight by about at least 10%, by at least 15% or by at least 20%.

55 . The method of any claim 40-54 , wherein the treatment reduces lean body mass by less than about 25%.

56 . The method of any claim 40-55 , wherein the human being in need thereof has an HbA1C value of about 5.7% to 6.4%.

57 . The method of claim 40-56 , wherein the human being in need thereof has an HbA1C value of about 4.0% to 5.6%.

58 . The method of claim 40-57 , wherein the pharmaceutical dosage formulation comprises about 1.2 mg of the peptide product.

59 . The method of claim 40-58 , wherein the pharmaceutical dosage formulation comprises about 1.8 mg of the peptide product.

60 . The method of claim 40-59 , wherein the pharmaceutical dosage formulation comprises about 2.4 mg of the peptide product.

61 . The method of claim 40-60 , wherein the pharmaceutical dosage formulation comprises (2.4 mg/ml; 0.24% (w/w)) of the peptide product; Mannitol (42.6 mg/mL; 4.26% (w/w)); Arginine (3.48 mg/mL; 0.348% (w/w)); and polysorbate 20 (2 mg/mL; 0.2% (w/w)) in sterile water.

62 . The method of claim 40-61 , wherein the pharmaceutical dosage formulation comprises (1.8 mg/ml; 0.18% (w/w)) of the peptide product; Mannitol (42.6 mg/mL; 4.26% (w/w)); Arginine (3.48 mg/mL; 0.348% (w/w)); and polysorbate 20 (2 mg/mL; 0.2% (w/w)) in sterile water.

63 . The method of claim 40-62 , wherein the pharmaceutical dosage formulation comprises (1.2 mg/ml; 0.12% (w/w)) of the peptide product; Mannitol (42.6 mg/mL; 4.26% (w/w)); Arginine (3.48 mg/mL; 0.348% (w/w)); and polysorbate 20 (2 mg/mL; 0.2% (w/w)) in sterile water.

64 . The method of claim 40-63 , wherein the treatment reduces one or more of serum triglycerides, total serum cholesterol, serum LDL, or serum VLDL.

65 . The method of claim 40-64 , wherein the treatment reduces serum triglycerides by at least about 20% after 48 weeks.

66 . The method of claim 40-65 , wherein the treatment reduces serum triglycerides by at least about 30% after 48 weeks.

67 . The method of claim 40-66 , wherein the treatment reduces total serum cholesterol by at least about 10% after 48 weeks.

68 . The method of claim 40-67 , wherein the treatment reduces total serum cholesterol by at least about 15% after 48 weeks.

69 . The method of claim 40-68 , wherein the treatment reduces serum LDL by at least about 10% after 48 weeks.

70 . The method of claim 40-69 , wherein the treatment reduces serum LDL by at least about 20% after 48 weeks.

71 . The method of claim 40-70 , wherein the treatment reduces serum VLDL by at least about 25% after 48 weeks.

72 . The method of claim 40-71 , wherein the treatment reduces serum triglycerides by at least about 30% after 48 weeks in human being in need thereof with >150 mg/dL triglycerides at baseline.

73 . The method of claim 40-72 , wherein the treatment reduces serum triglycerides by at least about 50% after 48 weeks in human being in need thereof with >150 mg/dL triglycerides at baseline.

74 . The method of claim 40-73 , wherein the treatment reduces serum cholesterol by at least about 15% after 48 weeks in human being in need thereof with >200 mg/dL cholesterol at baseline.

75 . The method of claim 40-74 , wherein the treatment reduces serum cholesterol by at least about 20% after 48 weeks in human being in need thereof with >200 mg/dL cholesterol at baseline.

76 . The method of claim 40-75 , wherein the treatment reduces serum LDL by at least about 15% after 48 weeks in human being in need thereof with >130 mg/dL LDL at baseline.

77 . The method of claim 40-76 , wherein the treatment reduces serum LDL by at least about 20% after 48 weeks in human being in need thereof with >130 mg/dL LDL at baseline.

78 . The method of claim 40-77 , wherein a steady state therapeutic dose is achieved after a dose escalating phase having a duration of from two to four weeks.