Provided herein are methods of improving glycemic control, reducing weight, and/or treating type 2 diabetes mellitus in human patients comprising administering GLP-1/glucagon agonist peptides, dapagliflozin, and metformin.

A method for improving the solubility of a physiologically active protein or peptide compared to that of a physiologically active protein or peptide which is not conjugated to an immunoglobulin Fc fragment is disclosed. The method includes steps of conjugating the physiologically active protein or peptide to an immunoglobulin Fc fragment. Also disclosed is a composition for improving the solubility of a physiologically active protein or peptide, which contains an immunoglobulin Fc fragment. The composition improves the solubility compared to a composition without an immunoglobulin Fc fragment.

A method for improving the solubility of a physiologically active protein or peptide compared to that of a physiologically active protein or peptide which is not conjugated to an immunoglobulin Fc fragment is disclosed. The method includes steps of conjugating the physiologically active protein or peptide to an immunoglobulin Fc fragment. Also disclosed is a composition for improving the solubility of a physiologically active protein or peptide, which contains an immunoglobulin Fc fragment. The composition improves the solubility compared to a composition without an immunoglobulin Fc fragment.

The disclosure provides a GLP-1 agonist polypeptide compound having an amino acid sequence: H Xaa.sup.1EGTFTSDVSSYLE Xaa.sup.2QAA Xaa.sup.3EFIAWLVRGRG (SEQ ID NO: 1). The C-terminal amino acid of the polypeptide compound is a carboxyl or the carboxyl is amidated. Xaa.sup.1 and Xaa.sup.2 are the same or different; R.sub.1 is: a straight-chain or branched-chain alkyl containing 2-6 carbon atoms, R.sub.2 is: H or CH.sub.3, X is: O, S or N—CH.sub.3, in the formula, R.sub.1 and R.sub.2 alkyl is optionally substituted by 1-6 halogen atoms.

The disclosure provides a GLP-1 agonist polypeptide compound having an amino acid sequence: H Xaa.sup.1EGTFTSDVSSYLE Xaa.sup.2QAA Xaa.sup.3EFIAWLVRGRG (SEQ ID NO: 1). The C-terminal amino acid of the polypeptide compound is a carboxyl or the carboxyl is amidated. Xaa.sup.1 and Xaa.sup.2 are the same or different; R.sub.1 is: a straight-chain or branched-chain alkyl containing 2-6 carbon atoms, R.sub.2 is: H or CH.sub.3, X is: O, S or N—CH.sub.3, in the formula, R.sub.1 and R.sub.2 alkyl is optionally substituted by 1-6 halogen atoms.

A novel long-acting acylated oxyntomodulin peptide analogue having dual agonism on GLP-1 and glucagon receptors (dual GLP-1R/GlucagonR agonism) and a pharmaceutical composition including the same are disclosed. The novel long-acting acylated oxyntomodulin peptide analogue and the composition are useful for the prevention and treatment of obesity and overweight, or non-insulin-dependent diabetes accompanied by obesity and overweight. The acylated oxyntomodulin peptide analog has dual agonism for GLP-1/glucagon receptors and has an excellent increased in vivo half-life, and the pharmaceutical composition containing the same is useful for the treatment of metabolic diseases such as obesity and diabetes.

A novel long-acting acylated oxyntomodulin peptide analogue having dual agonism on GLP-1 and glucagon receptors (dual GLP-1R/GlucagonR agonism) and a pharmaceutical composition including the same are disclosed. The novel long-acting acylated oxyntomodulin peptide analogue and the composition are useful for the prevention and treatment of obesity and overweight, or non-insulin-dependent diabetes accompanied by obesity and overweight. The acylated oxyntomodulin peptide analog has dual agonism for GLP-1/glucagon receptors and has an excellent increased in vivo half-life, and the pharmaceutical composition containing the same is useful for the treatment of metabolic diseases such as obesity and diabetes.

The present invention provides processes and compounds for the preparation of glucagon and GLP-1 co-agonist compounds that are useful in the treatment of type 2 diabetes, obesity, nonalcoholic fatty liver disease (NAFLD) and/or nonalcoholic steatohepatitis (NASH).

The present invention provides processes and compounds for the preparation of glucagon and GLP-1 co-agonist compounds that are useful in the treatment of type 2 diabetes, obesity, nonalcoholic fatty liver disease (NAFLD) and/or nonalcoholic steatohepatitis (NASH).

An incretin analogue, a preparation method therefor, and the use thereof. The incretin analogue has a GLP-1R/GIPR/GCGR agonist activity, is a triple agonist, and can be used for lowering blood glucose, reducing fat and reducing weight.