Abstract: The present invention relates to exendin-4 derivatives and their medical use, for example in the treatment of disorders of the metabolic syndrome, including diabetes and obesity, as well as reduction of excess food intake.

Abstract: Provided herein are peptides and variant peptides that exhibit enhanced activity at the GLP-1 receptor, as compared to native glucagon.

Abstract: Provided herein are methods and compositions to achieve a sustained delay in the progression of, or an amelioration of diabetes in a subject, or a delay in diabetes onset in a subject at risk for diabetes, comprising an abbreviated course of administration of a pharmaceutical composition comprising an exendin or an exendin agonist analog in an amount effective to induce ? cell regeneration.

Abstract: Prodrug formulations of glucagon superfamily peptides are provided wherein the glucagon superfamily peptide has been modified by the linkage of a dipeptide to the glucagon superfamily through an amide bond linkage. The prodrugs disclosed herein have extended half lives and are converted to the active form at physiological conditions through a non-enzymatic reaction driven by chemical instability.

Abstract: A method for inhibiting dipeptidyl-peptidase IV is provided and includes administering a peptide to the dipeptidyl-peptidase IV, in which the peptide is isolated from a gelatin hydrolysate produced by enzymatic digestion with alcalase (ALA), bromelain (BRO), and flavourzyme (FLA).

Abstract: Novel protracted exendin-4 compounds and therapeutic uses thereof.

Abstract: The present invention relates to use of GLP-1 or a related molecule having GLP-effect for the manufacture of a medicament for preventing or treating diabetes in a mammal. The amount and timing of administration of said medicament are subsequently reduced to produce a “drug holiday”. Practice of the invention achieves effective therapy without continuous drug exposure and without continuous presence of therapeutic levels of the drug. The invention also discloses a method of treating diabetes and related disorders in a mammal by administering glucagon like peptide (GLP-1) or a related molecule having GLP-1 like effect and thereby providing a therapeutically effective amount of endogenous insulin.

Abstract: Oligosaccharide chain added GLP-1 peptides are more stable in blood and more active in controlling blood-sugar levels than GLP-1 peptides without added oligosaccharides. Oligosaccharide chain added GLP-1 peptides having GLP-1 activity include at least one or at least two amino acids each substituted with an oligosaccharide chain added amino acid in GLP-1; a peptide having the amino acid sequence of GLP-1 with deletion, substitution or addition of one or several amino acids; or a GLP-1 analog. Oligosaccharide chain added GLP-1 peptides with at least one amino acid substituted with an oligosaccharide chain added amino acid include an oligosaccharide chain with oligo hyaluronic acid. Oligosaccharide chain added amino acids include oligosaccharide chains attached to amino acids via linkers.

Abstract: Peptide-peptidase inhibitor conjugate molecules are disclosed. These conjugate molecules are useful as agents for the treatment and prevention of metabolic and cardiovascular diseases, disorders, and conditions. Such diseases, conditions and disorders include, but are not limited to, hypertension, dyslipidemia, cardiovascular disease, eating disorders, insulin-resistance, obesity, and diabetes mellitus of any kind, and other diabetes-related disorders.

Abstract: The present invention relates to the field of metabolic compound conjugates, methods of forming said conjugates and uses of these conjugates in the treatment of diabetes and conditions related to this condition. The metabolic compound conjugates of this invention include a metabolic peptide having a glucagon-like peptide (GLP-1) receptor binding motif for action on a GLP-1 receptor and at least one oligomer conjugation site for binding with at least one oligomer, wherein the oligomer includes a polyethylene glycol moiety (PEG), and/or alkyl moiety.

Abstract: The disclosure provides N-terminus conformationally constrained compounds, which may comprise peptide mimetics and/or amino acid substitutions, which may be used in peptides, such as GLP-1 receptor agonist compounds, to induce ?-turn secondary structure at the N-terminus. The N-terminus conformationally constrained compounds may be used for research purposes; to produce GLP-1 receptor agonist compounds having improved GLP-1 receptor binding activity, enzymatic stability, or in vivo glucose lowering activity; and to develop GLP-1 receptor agonist compounds which have fewer amino acid residues. The disclosure also provides GLP-1 receptor agonist compounds, such as exendins, exendin analogs, GLP-1(7-37), GLP-1(7-37) analogs, comprising the N-terminus conformationally constrained compounds. The compounds are useful for treating various diseases, such as diabetes and obesity. The disclosure also provides methods for chemically synthesizing the N-terminus conformationally constrained compounds.

Abstract: The present invention provides pharmaceutical compositions comprising at least one polypeptide having GLP-1 activity wherein an effective dose of said pharmaceutical composition comprises 15 mg, 30 mg, 50 mg or 100 mg of said polypeptide having GLP-1 activity. Also provided are methods of administering the pharmaceutical compositions of the invention.

Abstract: Stable pharmaceutical composition comprising insulinotropic peptide.

Abstract: Methods and compositions for treating patients (e.g., patients who are insulin resistant, patients who have diabetes, or are at risk for developing diabetes) are disclosed herein. The methods can include administration of an ?1 antitrypsin (AAT) polypeptide or an agent, such as a nucleic acid molecule or organic compound, that promotes the expression or activity of ?1-antitrypsin.

Abstract: The present invention refers to the use of Lixisenatide or/and a pharmaceutically acceptable salt thereof, for the manufacture of a medicament for the treatment of diabetes mellitus type 2, for inducing weight loss in diabetes type 2 patients or/and for preventing weight gain in diabetes type 2 patients.

Abstract: The present invention refers to a pharmaceutical combination for use in inducing weight loss in diabetes type 2 patients or/and for preventing weight gain in diabetes type 2 patients.

Abstract: The invention discloses site-specific mono-PEGylated Exendin analogs in which any amino groups can be mono-PEGylated as well as their preparation method and use. The method of the present invention adopts a more stable protective group Dde (N-?-1-(4,4-dimethyl-2,6-dioxo-cyclohexylene)) to avoid multi-PEGylated side reactions rendered by unstable protecting groups, achieving mono-PEGylated Exendin analogs at a high recovery with a low reaction molar ratio.

Abstract: The invention is directed to a pharmaceutical composition comprising at least one FGF-21 (fibroblast growth factor 21) compound, at least one GLP-1R (glucagon-like peptide-1 receptor) agonist and optionally at least one anti-diabetic drug and/or at least one DPP-4 (dipeptidyl peptidase-4) inhibitor for the treatment of at least one metabolic syndrome and/or atherosclerosis, in particular diabetes, dyslipidemia, obesity and/or adipositas. The invention is also directed to a pharmaceutical composition comprising at least one FGF-21 (fibroblast growth factor 21) compound, at least one DPP-4 (dipeptidyl peptidase-4) inhibitor and optionally GLP-1R (glucagon-like peptide-1 receptor) agonist and/or at least one at least one anti-diabetic drug for the treatment of at least one metabolic syndrome and/or atherosclerosis, in particular diabetes, dyslipidemia, obesity and/or adipositas.

Abstract: Methods are provided for coating crystalline microparticles with an active agent by altering the surface properties of the microparticles in order to facilitate favorable association on the microparticle by the active agent. Type of surface properties that are altered by the disclosed methods include by electrostatic properties, hydrophobic properties and hydrogen bonding properties.

Abstract: Prodrug formulations of glucagon superfamily peptides are provided wherein the glucagon superfamily peptide has been modified by the linkage of a dipeptide to the glucagon superfamily through an amide bond linkage. The prodrugs disclosed herein have extended half lives and are converted to the active form at physiological conditions through a non-enzymatic reaction driven by chemical instability.

Abstract: Provided herein are peptides and variant peptides that exhibit enhanced activity at the GLP-1 receptor, as compared to native glucagon.

Abstract: The present invention discloses a modified exendin or pharmaceutically acceptable salts thereof, wherein the modified exendin comprises an amino acid sequence having at least 90% sequence identity to SEQ ID No. 17 and the amino acid sequence has a higher stability than the non-modified exendin of SEQ ID No. 4. These compounds are useful in treating type 2 diabetes as GLP-1 receptor agonists.

Abstract: Physical crystal structures of a compound of the formula I: are provided including the free base monohydrate thereof (form H-1) and the hydrochloric acid salt thereof, including hydrochloric acid salt containing 0.75 equivalent of H2O (form H0.75-3) and hydrochloric acid salt containing 2 equivalents of H2O (form H2-1), and hydrochloric acid salt Pattern P-5, preferably in substantially pure form, and other forms as described herein, pharmaceutical compositions containing structures of compound I or IA, processes for preparing same, intermediates used in preparing same, and methods of treating diseases such as diabetes using such structures.

Abstract: Disclosed are compositions and methods for increasing diabetes resolution in a diabetic patient having undergone gastric restrictive surgery, entailing use of active agent that produces an incretin-like effect in the patient.

Abstract: A milk protein hydrolysate which is preferably caseinoglycomacropeptide and/or a whey protein in a bioavailable form is used for the manufacture of a composition for the treatment or prevention of diabetes or syndrome X. The invention also relates to a method of treatment or prevention of diabetes or syndrome X utilizing such compositions, a method for assessing proglucagon gene expression and GLP-1 release by a cell line derived from an adenocarcinoma of human caecum.

Abstract: Provided herein are glucagon analogs comprising a modified amino acid sequence of native human glucagon (SEQ ID NO: 2) that exhibit activity at the glucagon receptor, activity at the GLP-1 receptor, or activity at each of the glucagon receptor and the GLP-1 receptor. In some embodiments, the glucagon analog exhibits at least 100% or more of the activity of native glucagon at the glucagon receptor and/or at least 100% or more of the activity of native GLP-1 at the GLP-1 receptor. In some embodiments, the glucagon analog has an EC50 at the GLP-1 receptor which is within 50-fold or less than the EC50 at the glucagon receptor. In some embodiments, the glucagon analog has an EC50 at the GLP-1 receptor which is two- to ten-fold greater than the EC50 at the glucagon receptor. Related conjugates, dimers and multimers, and pharmaceutical compositions, and uses thereof, are further provided.

Abstract: Compounds are provided having inter alia good duration of action, high potency and/or convenient dosing regimens including oral administration. The compounds are engineered polypeptides which incorporate an albumin binding domain in combination with one or more biologically active polypeptides. Also provided are pharmaceutical compositions and methods of treatment for diseases and disorders including obesity and overweight, diabetes, dyslipidemia, hyperlipidemia, Alzheimer's disease, fatty liver disease, short bowel syndrome, Parkinson's disease, cardiovascular disease, and other and disorders of the central nervous system.

Abstract: Methods and compositions are provided for evaluating a diabetic patient for treatment with an incretin-based therapy. In certain embodiments, evaluation is ongoing and the patient is evaluated at multiple times. In additional embodiments, a diabetic patient is treated with an incretin-based therapy after the patient has been evaluated for expression levels of GLP-1R in a biological sample. In some aspects, the biological sample is specifically a blood sample that has been enriched for peripheral blood monocytes.

Abstract: Provided herein are peptide combinations comprising a GIP agonist peptide and a glucagon antagonist peptide. In some embodiments, the peptide combination is provided as a composition, e.g., a pharmaceutical composition, while in other embodiments, the peptide combination is provided as a kit. In yet other embodiments, the peptide combination is provided as a conjugate, e.g., a fusion peptide, a heterodimer. In specific aspects, the GIP agonist peptide is an analog of native human glucagon. In specific aspects, the glucagon antagonist peptide is an analog of native human glucagon. In some embodiments, the GIP agonist peptide is covalently attached to the glucagon antagonist peptide via a linker. Method of treating a disease, e.g., a metabolic disorder, such as diabetes and obesity, comprising administering the peptide compositions described herein are further provided.

Abstract: The present invention relates generally to novel, selectable hybrid polypeptides useful as agents for the treatment and prevention of metabolic diseases and disorders which can be alleviated by control plasma glucose levels, insulin levels, and/or insulin secretion, such as diabetes and diabetes-related conditions. Such conditions and disorders include, but are not limited to, hypertension, dyslipidemia, cardiovascular disease, eating disorders, insulin-resistance, obesity, and diabetes mellitus of any kind, including type 1, type 2, and gestational diabetes.

Abstract: The 30 amino acid peptide GLP-1 has been integrated into the stable host protein human calbindin D9k. The fusion protein binds to GLP-1R. The fusion protein agents can be useful for both diabetes treatment and GLP-1R receptor targeting MR imaging. The fusion protein comprises a first peptide that selectively binds to a site of a target cell and linked to a second peptide, where the fusion protein is more stable than the first peptide alone and may further comprise a detectable label. The first peptide of the fusion protein may be glucagon-like peptide-1 (GLP-1), glucagon-like peptide-1 (GLP-1)(7-36), or glucagon-like peptide-1 (GLP-1) (9-36), or a conservative variant thereof.

Abstract: The present invention relates to exendin-4 derivatives and their medical use, for example in the treatment of disorders of the metabolic syndrome, including diabetes and obesity, as well as reduction of excess food intake.

Abstract: The invention relates to a pharmaceutical composition according to the claim 1 comprising an SGLT2 inhibitor and a GLP-1 receptor agonist which is suitable in the treatment or prevention of diabetes mellitus, impaired glucose tolerance, hyperglycemia or other conditions. In addition the present invention relates to methods for preventing or treating of metabolic disorders and related conditions.

Abstract: A composition for the prevention or treatment of type I diabetes in a subject, said composition comprising a GABAergic and incretin exemplified by GABA and GLP-1/Ex4. These are optionally provided together in a single composition to promote beta-cell regeneration prevent beta-cell apoptosis and control autoimmunity for the prevention and treatment of T1D in mammals.

Abstract: The present invention provides a compound of Formula (I) a pharmaceutically salt thereof wherein R1, R2, Ra, L, Z, Z1 and Z2 are as defined herein, that act as Ghrelin antagonists or inverse agonists; pharmaceutical compositions thereof; and methods of treating diseases, disorders, or conditions mediated by the antagonism of the Ghrelin receptor.

Abstract: The invention is directed to a fusion protein comprising at least one FGF-21 (fibroblast growth factor-21) compound and at least one GLP-1R (glucagon-like peptide-1 receptor) agonist as well as to pharmaceutical compositions, medical uses and methods of treatment involving the fusion protein, particularly in the field of diabetes, dyslipidemia, obesity and/or adipositas.

Abstract: Modified glucagon peptides are disclosed having improved solubility while retaining glucagon agonist activity. The glycogen peptides have been modified by substitution of native amino acids with, and/or addition of, charged amino acids to the carboxy terminus of the peptide. The modified glucagon agonists can be further modified by pegylation, or the addition of a carboxy terminal peptide selected from the group consisting of SEQ ID NO: 20, SEQ ID NO: 21, SEQ ID NO: 23, or both to further enhance the solubility of the glucagon agonist analogs.

Abstract: The present invention relates to methods and pharmaceutical compositions relating to administering hypoglycemic agents and/or GLP-1 agonists wherein the mean maximum plasma concentration (Cmax) and/or Area Under the Curve (AUC) values of the hypoglycemic agent are increased and/or sustained.

Abstract: The present invention relates to pharmaceutical compositions comprising {2-[3-cyclohexyl-3-(trans-4-propoxy-cyclohexyl)-ureido]-thiazol-5-ylsulfanyl}-acetic acid (FRI-1) in combination with an anti-diabetic drug selected from the group consisting of metformin, sitagliptin or exenatide. The present invention also relates to the use of the pharmaceutical compositions in restoring insulin sensitivity and treating type II diabetes, including reducing body weight in subjects undergoing type II diabetes treatment.

Abstract: The disclosure provides Polypeptide Conjugates with multiple improved pharmacological and pharmacokinetic properties and their use in treating various diseases and conditions, such as diabetes and/or obesity.

Abstract: A method for treating or preventing a disease, condition or state in a subject in need thereof by administering to the subject an effective amount of the (?)-enantiomer of perhexyline or a pharmaceutically acceptable salt, prodrug or derivative thereof, substantially free of the (+)-enantiomer, or pharmaceutical composition containing same. The disease, condition or state may be associated with altered tissue energetics, impaired tissue energetics, altered cardiac tissue energetics, impaired cardiac tissue energetics, altered hepatic tissue energetics, impaired hepatic tissue energetics, and diabetes.

Abstract: Novel compounds of the structural formula (I), and the pharmaceutically acceptable salts thereof, are agonists of G-protein coupled receptor 40 (GPR40) and may be useful in the treatment, prevention and suppression of diseases mediated by the G-protein-coupled receptor 40. The compounds of the present invention may be useful in the treatment of Type 2 diabetes mellitus, and of conditions that are often associated with this disease, including obesity and lipid disorders, such as mixed or diabetic dyslipidemia, hyperlipidemia, hypercholesterolemia, and hypertriglyceridemia.

Abstract: The invention relates to a derivative of a GLP-1 analogue, which analogue comprises a first K residue at a position corresponding to position 37 of GLP-1(7-37) (SEQ ID NO: 1), a second K residue at a position corresponding to position 26 of GLP-1(7-37), and a maximum of ten amino acid modifications as compared to GLP-1(7-37), wherein the first K residue is designated K37, and the second K residue is designated K26, which derivative comprises two albumin binding moieties attached to K26 and K37, respectively, wherein the albumin binding moiety comprises a protracting moiety selected from: Chem. 1, Chem. 2, Chem. 3 or Chem. 4; or a pharmaceutically acceptable salt, amide, or ester thereof.

Abstract: The invention relates to a pharmaceutical composition comprising 1.a and/or 1.b according to claim 1 in combination with at least one second therapeutic agent 2 which is suitable in the treatment or prevention of one or more conditions selected from type 1 diabetes mellitus, type 2 diabetes mellitus, impaired glucose tolerance and hyperglycemia. In addition the present invention relates to methods for preventing or treating of metabolic disorders and related conditions.

Abstract: Novel modified exendins and exendin agonists having an exendin or exendin agonist linked to one or more polyethylene glycol polymers, for example, and related formulations and dosages and methods of administration thereof are provided. These modified exendins and exendin agonists, compositions and methods are useful in treating diabetes and conditions that would be benefited by lowering plasma glucose or delaying and/or slowing gastric emptying or inhibiting food intake.

Abstract: The disclosure provides N-terminus conformationally constrained compounds, which may comprise peptide mimetics and/or amino acid substitutions, which may be used in peptides, such as GLP-1 receptor agonist compounds, to induce a ?-turn secondary structure at the N-terminus. The N-terminus conformationally constrained compounds may be used for research purposes; to produce GLP-1 receptor agonist compounds having improved GLP-1 receptor binding activity, enzymatic stability, or in vivo glucose lowering activity; and to develop GLP-1 receptor agonist compounds which have fewer amino acid residues. The disclosure also provides GLP-1 receptor agonist compounds, such as exendins, exendin analogs, GLP-1 (7-37), GLP-1 (7-37) analogs, comprising the N-terminus conformationally constrained compounds. The compounds are useful for treating various diseases, such as diabetes and obesity. The disclosure also provides methods for chemically synthesizing the N-terminus conformationally constrained compounds.

Abstract: The invention provides materials and methods for promoting weight loss or preventing weight gain, and in the treatment of diabetes, metablic syndrome and associated disorders. In particular, the invention provides novel glucagon analogue peptides effective in such methods. The peptides may mediate their effect by having increased selectivity for the GLP-1 receptor as compared to human glucagon.

Abstract: The invention provides materials and methods for promoting weight loss or preventing weight gain, and in the treatment of diabetes, metabolic syndrome and associated disorders. In particular, the invention provides novel glucagon analogue peptides effective in such methods. The peptides may mediate their effect by having increased selectivity for the GLP-1 receptor as compared to human glucagon.

Abstract: An effective combination of 6.25-100 mg of acarbose with a GLP-1 mimetic, such as 5-10 mg exenatide or 0.3-3.0 mg liraglutide.

Abstract: The present invention relates to novel glucagon peptides with improved stability and solubility at neutral pH, to the use of the compounds in therapy, to methods of treatment comprising administration of the compounds to patients in need thereof, and to the use of the compounds in the manufacture of medicaments. The glucagon peptides of the invention are of particular interest in relation to the treatment of hyperglycemia, diabetes and obesity, as well as a variety of diseases or conditions associated with hyperglycemia, diabetes and obesity.