Abstract: Polypeptides are provided that have activity at each of the GIP, GLP-1 and glucagon receptors. The polypeptides have structural features resulting in activity and extended duration of action at each of these receptors. Methods also are provided for treating diseases and/or conditions such as obesity, chronic weight management, type 2 diabetes mellitus, non-alcoholic fatty liver disease (NAFLD), non-alcoholic steatohepatitis (NASH), dyslipidemia, metabolic syndrome, Chronic Kidney Disease (CKD), osteoarthritis (OA), obesity-related sleep apnea (OSA) and polycystic ovary syndrome (PCOS).

Abstract: The presently described compounds relate to the treatment of Type I and/or Type II diabetes and/or hyperglycemia. More particularly, the described compounds relate to extended time action acylated insulin compounds that lower blood glucose, pharmaceutical compositions containing such compounds, therapeutic uses of such compounds, and an intermediate compound used to make the acylated insulin compounds.

Abstract: Fatty acid-acylated insulin analogs are soluble at moderately acidic pH and provide long-acting basal control of glucose levels. In such a molecule, the insulin analog portion comprises an insulin A-chain, or an analog thereof, properly cross-linked to an analog of the insulin B-chain, wherein the &egr;-amino group of a Lys residue at either positions 28 or 29 of the B-chain analog is acylated with a fatty acid. The insulin analog portion of the molecules comprises an A-chain of insulin, or an analog thereof, with an optional Arg at position 0, properly cross-linked to a B-chain analog that includes Arg at positions 31 and 32.