The present invention relates to the discovery of small molecule compounds that act as GLP-1R agonists and/or as positive allosteric modulators (PAMs) of GLP-1R. Such compounds are useful to treat, ameliorate, and/or prevent insulin resistance and/or diabetes in a mammal.

The present invention relates to the discovery of small molecule compounds that act as GLP-1R agonists and/or as positive allosteric modulators (PAMs) of GLP-1R. Such compounds are useful to treat, ameliorate, and/or prevent insulin resistance and/or diabetes in a mammal.

Pharmaceutical compositions useful in the treatment of metabolic disorders including diabetes, the compositions comprising a) a dipeptidyl peptidase IV (DPP IV) inhibitor such as sitagliptin, b) a biguanide such as metformin, and c) a sulfonylurea such as glimepiride, wherein each one of the DPPIV inhibitor, biguanide and sulfonylurea are at a dose that is at about 20-75% of the lowest diabetes therapeutic dose (LDTD).

Pharmaceutical compositions useful in the treatment of metabolic disorders including diabetes, the compositions comprising a) a dipeptidyl peptidase IV (DPP IV) inhibitor such as sitagliptin, b) a biguanide such as metformin, and c) a sulfonylurea such as glimepiride, wherein each one of the DPPIV inhibitor, biguanide and sulfonylurea are at a dose that is at about 20-75% of the lowest diabetes therapeutic dose (LDTD).

Pharmaceutical compositions useful in the treatment of metabolic disorders including diabetes, the compositions comprising a) a dipeptidyl peptidase IV (DPP IV) inhibitor such as sitagliptin, b) a biguanide such as metformin, and c) a sulfonylurea such as glimepiride, wherein each one of the DPPIV inhibitor, biguanide and sulfonylurea are at a dose that is at about 20-75% of the lowest diabetes therapeutic dose (LDTD).

At least five classes of MNP-based compounds have been demonstrated to form supramolecular particles for effective delivery by injection or topically of different types of therapeutic, prophylactic, or diagnostic agents. These compounds are isolated from natural sources such as plants. Exemplary MNP-based compounds, from which synthetic analogs or derivatives are made and appreciated to function similarly, e.g., capable of forming supramolecular particles include diterpene resin acids (e.g., abietic acid and pimaric acid), phytosterols (e.g., stigmasterol and β-sitosterol), lupane-type pentacyclic triterpenes (e.g., lupeol and betulinic acid), oleanane-type pentacyclic tritepenes (e.g., glycyrrhetic acid and sumaresinolic acid), and lanostane-type triterpenes and derivatives (e.g., dehydrotrametenolic acid and poricoic acid A). In some cases the MNP-based compounds are therapeutically effective in the absence of added therapeutic, prophylactic or diagnostic agent. Betulinic acid (BA) NPs were capable of efficiently penetrating ischemic brains and effectively promoting functional recovery as antioxidant agents.

At least five classes of MNP-based compounds have been demonstrated to form supramolecular particles for effective delivery by injection or topically of different types of therapeutic, prophylactic, or diagnostic agents. These compounds are isolated from natural sources such as plants. Exemplary MNP-based compounds, from which synthetic analogs or derivatives are made and appreciated to function similarly, e.g., capable of forming supramolecular particles include diterpene resin acids (e.g., abietic acid and pimaric acid), phytosterols (e.g., stigmasterol and β-sitosterol), lupane-type pentacyclic triterpenes (e.g., lupeol and betulinic acid), oleanane-type pentacyclic tritepenes (e.g., glycyrrhetic acid and sumaresinolic acid), and lanostane-type triterpenes and derivatives (e.g., dehydrotrametenolic acid and poricoic acid A). In some cases the MNP-based compounds are therapeutically effective in the absence of added therapeutic, prophylactic or diagnostic agent. Betulinic acid (BA) NPs were capable of efficiently penetrating ischemic brains and effectively promoting functional recovery as antioxidant agents.

A series of pharmaceutical compositions containing polypeptide dual agonist compounds and pharmaceutically acceptable salts thereof, wherein same have dual agonist effects on a human glucagon-like peptide-1 (GLP-1) receptor and a human blood glucose-dependent insulinotropic polypeptide (GIP) receptor, and can be used for treating non-insulin-dependent diabetes, insulin-dependent diabetes, obesity and other related diseases.

A series of pharmaceutical compositions containing polypeptide dual agonist compounds and pharmaceutically acceptable salts thereof, wherein same have dual agonist effects on a human glucagon-like peptide-1 (GLP-1) receptor and a human blood glucose-dependent insulinotropic polypeptide (GIP) receptor, and can be used for treating non-insulin-dependent diabetes, insulin-dependent diabetes, obesity and other related diseases.

In some embodiments provided herein is a method of treating a coagulopathy in a subject that is being administered or has been administered an antiplatelet agent, the method comprising: (a) determining that the subject has an abnormal result for evaluation of one or more clotting parameters; and (b) after (a), administering to the subject in need thereof an effective amount of a composition comprising platelets or platelet derivatives and an incubating agent comprising one or more salts, a buffer, optionally a cryoprotectant, and optionally an organic solvent.