GLP-1R and GCGR Agonists, Formulations, and Methods of Use

1 . (canceled)

2 . A pharmaceutical dosage formulation comprising an agonist peptide with affinity for glucagon-like peptide 1 receptor (GLP-1R) and glucagon receptor (GCGR) wherein: the peptide is modified with a non-ionic glycolipid surfactant; the dosage is configured to induce weight loss with reduction of one or more adverse events as compared to an agonist with unbalanced affinity for GLP-1R and GCGR, the adverse events being selected from nausea, vomiting, diarrhea, abdominal pain and constipation, upon administration to a mammal.

3 - 7 . (canceled)

8 . The pharmaceutical dosage formulation of claim 2 wherein the dual agonist peptide is any one of SEQ ID NOS: 1-10 or 12-27.

9 . (canceled)

10 . The pharmaceutical dosage formulation of claim 2 , wherein the surfactant is a 1-alkyl glycoside class surfactant.

11 - 17 . (canceled)

18 . The pharmaceutical dosage formulation of claim 2 , wherein the concentration of the dual peptide agonist is 0.05 to 20 mg/ml.

19 - 27 . (canceled)

28 . The pharmaceutical dosage formulation of claim 2 configured such that the time to reach a therapeutic dose is about four weeks or less.

29 . The pharmaceutical dosage formulation of claim 28 wherein the therapeutic dose exhibits a C max of from about 10 to about 300 ng/ml; a T max of from about 10 to about 36 hours; and/or, an AUC 0-168 of from about 1,000 to 100,000 h*ng/mL.

30 . (canceled)

31 . A method for inducing weight loss in a mammal, the method comprising administering pharmaceutical dosage formulation of claim 2 to a mammal, wherein the method reduces the incidence of one of more adverse events as compared to an agonist with unbalanced affinity for GLP-1R and GCGR, the adverse events being selected from nausea, vomiting, diarrhea, abdominal pain and constipation, upon administration to a mammal.

32 - 34 . (canceled)

35 . The method of claim 31 , wherein the pharmaceutical dosage is administered is administered subcutaneously.

36 - 48 . (canceled)

49 . A pharmaceutical dosage formulation configured for subcutaneous administration comprising an agonist peptide with affinity for glucagon-like peptide 1 receptor (GLP-1R) and glucagon receptor (GCGR) wherein the peptide product is represented as SEQ ID NO: 1; the dosage is configured to induce weight loss with reduction of one or more adverse events as compared to an agonist with unbalanced affinity for GLP-1R and GCGR, the adverse events being selected from nausea, vomiting, diarrhea, abdominal pain and constipation, upon administration to a mammal.

50 . The pharmaceutical dosage formulation of claim 49 , wherein weight loss is at least 5%, at least 10%; or from about 1% to about 20%; or from about 5% to about 10% (w/w).

51 . The pharmaceutical dosage formulation of claim 49 , wherein the dosage is configured as a weekly dosage form, optionally configured for administration from about 2 weeks to about 8 weeks.

52 . (canceled)

53 . The pharmaceutical dosage formulation of claim 51 , wherein administration to a mammal of a single dose, as compared to administration of an approximate equimolar dosage of semaglutide, exhibits a lower C max at about 1 day, about 2 days, about 3 days, about 4 days, about 5 days, about 6 days or about 7 days following administration.

54 . The pharmaceutical dosage formulation of claim 49 , wherein the dosage is configured to administer to a human between about 0.1 to about 15 mg per week; optionally about 1 to about 7 mg per week; or optionally about 1 to 5 mg per week.

55 . The pharmaceutical dosage formulation of claim 49 configured to be administered to the mammal once weekly for at least, or up to six weeks.

56 . The pharmaceutical dosage formulation of claim 49 , wherein the dosage is configured to reach a therapeutic dose in about four weeks or less following first weekly administration.

57 . The pharmaceutical dosage formulation of claim 56 , wherein the therapeutic dose exhibits a C max of from about 10 to about 300 ng/ml, optionally a C max less than 200 ng/ml; a T max of from about 10 to about 36 hours; and/or, an AUC 0-168 of from about 1,000 to 100,000 h*ng/mL.

58 . A method for inducing weight loss in a mammal, the method comprising administering pharmaceutical dosage formulation of claim 49 to a mammal, wherein the method reduces the incidence of one of more adverse events as compared to an agonist with unbalanced affinity for GLP-1R and GCGR, the adverse events being selected from nausea, vomiting, diarrhea, abdominal pain and constipation, upon administration to a mammal at a therapeutic dose.

59 . The method of claim 58 , wherein the pharmaceutical dosage is administered about weekly wherein an initial dose is the therapeutic dose.

60 . The method of claim 58 , wherein the pharmaceutical dosage is administered about weekly from about 2 weeks to about 8 weeks, or longer.