Described herein are methods and compositions for treating diabetes mellitus, concerning oral pharmaceutical compositions comprising insulin in combination with a GLP-1 analogue.

Described herein are methods and compositions for treating diabetes mellitus, concerning oral pharmaceutical compositions comprising insulin in combination with a GLP-1 analogue.

A composition in the form of an injectable aqueous solution, the pH of which is from 3.0 to 4.4, including at least a rapid-acting insulin analog and at least one glucagon suppressor with prandial action. The glucagon suppressor with prandial action is selected from the group consisting of an amylin analog or an amylin receptor agonist or a GLP-1 analog or a GLP-1 receptor agonist (GLP-1 RA). The glucagon suppressor with prandial action is an amylin analog or an amylin receptor agonist. The glucagon suppressor peptide with prandial action is pramlintide.

Embodiments of the invention provide swallowable devices, preparations and methods for delivering therapeutic agents within the GI tract such as neutralizing proteins (NP) particularly antibodies which neutralize interleukins. Many embodiments provide a swallowable device e.g., a capsule for delivering various agents into the intestinal wall (IW). Embodiments also provide agent preparations that are configured to be contained within the capsule, advanced from the capsule into the IW and degrade to release the agent into the bloodstream to produce a therapeutic effect. The preparation can be operably coupled to delivery means having a first configuration where the preparation is contained in the capsule and a second configuration where the preparation is advanced out of the capsule into the IW. Embodiments of the invention are particularly useful for the delivery of interleukin NP's (INP) for treatment of inflammatory conditions where such INP's are poorly absorbed, tolerated and/or degraded within the GI tract.

Embodiments of the invention provide swallowable devices, preparations and methods for delivering therapeutic agents within the GI tract such as neutralizing proteins (NP) particularly antibodies which neutralize interleukins. Many embodiments provide a swallowable device e.g., a capsule for delivering various agents into the intestinal wall (IW). Embodiments also provide agent preparations that are configured to be contained within the capsule, advanced from the capsule into the IW and degrade to release the agent into the bloodstream to produce a therapeutic effect. The preparation can be operably coupled to delivery means having a first configuration where the preparation is contained in the capsule and a second configuration where the preparation is advanced out of the capsule into the IW. Embodiments of the invention are particularly useful for the delivery of interleukin NP's (INP) for treatment of inflammatory conditions where such INP's are poorly absorbed, tolerated and/or degraded within the GI tract.

Provided is a pharmaceutical composition for treating and/or preventing fatty liver disease, particularly nonalcoholic fatty liver disease, the pharmaceutical composition having an excellent ACC2-selective inhibitory action and having no side effects such as an increase in plasma triglyceride or a decrease in platelet concentration.

A pharmaceutical composition for treating and/or preventing fatty liver disease, the pharmaceutical composition comprising a compound represented by Formula (I):

##STR00001## wherein R.sup.1 is haloalkyl or non-aromatic carbocyclyl, R.sup.2 is a hydrogen atom or halogen, R.sup.3 is halogen, ring A is a group represented by the formula:

##STR00002## -L.sup.1- is —O—(CH.sub.2)—, —(CH.sub.2).sub.2—, or the like, R.sup.4 is alkyl or haloalkyl, and R.sup.5 is alkylcarbonyl or carbamoyl, or a pharmaceutically acceptable salt thereof.

Provided herein are spirolactone compounds of Formula I that are useful as inhibitors of ACC1 and/or ACC2. The spirolactone compounds described herein can be used for treating a disease or disorder associated with aberrant ACC1 and/or ACC2 activities, for example, non-alcoholic steatohepatitis (NASH), acne, obesity, diabetes, and cancer. Also provided herein are pharmaceutical compositions comprising the spirolactone compound of Formula I, or pharmaceutically acceptable salt thereof. ##STR00001##

Provided herein are spirolactone compounds of Formula I that are useful as inhibitors of ACC1 and/or ACC2. The spirolactone compounds described herein can be used for treating a disease or disorder associated with aberrant ACC1 and/or ACC2 activities, for example, non-alcoholic steatohepatitis (NASH), acne, obesity, diabetes, and cancer. Also provided herein are pharmaceutical compositions comprising the spirolactone compound of Formula I, or pharmaceutically acceptable salt thereof. ##STR00001##

Incretin analogs are provided that have activity at each of the GIP, GLP-1 and glucagon receptors. The incretin analogs have structural features resulting in balanced activity and extended duration of action at each of these receptors. Methods also are provided for treating diseases such as diabetes mellitus, dyslipidemia, fatty liver disease, metabolic syndrome, non-alcoholic steatohepatitis and obesity.

The disclosure provides peptide products comprising a peptide covalently attached to a surfactant moiety which have improved properties, including increased duration of action and bioavailability. The peptide products are useful for treating insulin resistance, diabetes, obesity, metabolic syndrome and cardiovascular diseases, and conditions associated therewith, such as NASH and PCOS.