Pioglitazone

Pioglitazone is an oral antihyperglycemic agent that acts primarily by decreasing insulin resistance. Chemically, pioglitazone is prepared as hydrochloride salt, which is identified as (±)-5-[[4-[2-(5-ethyl-2-pyridinyl)ethoxy]phenyl]methyl]-2,4-thiazolidinedione monohydrochloride. It has a molecular formula of C19 H20 N2 O3 S•HCl and a molecular weight of 392.90 daltons. The structural formula is:

Pioglitazone hydrochloride is an odorless white crystalline powder that contains one asymmetric carbon in the thiazolidinedione moiety. The synthetic compound is a racemate and the two enantiomers of pioglitazone interconvert in vivo. It is soluble in N,N dimethylformamide, slightly soluble in anhydrous ethanol, very slightly soluble in acetone and acetonitrile, practically insoluble in water and insoluble in ether.

OSENI is available as a fixed-dose combination tablet for oral administration containing 34 mg alogliptin benzoate equivalent to 25 mg alogliptin and any of the following strengths of pioglitazone hydrochloride:
16.53 mg pioglitazone hydrochloride equivalent to 15 mg pioglitazone (25 mg/15 mg)
•
33.06 mg pioglitazone hydrochloride equivalent to 30 mg pioglitazone (25 mg/30 mg)
•
49.59 mg pioglitazone hydrochloride equivalent to 45 mg pioglitazone (25 mg/45 mg)
OSENI is also available as a fixed-dose combination tablet for oral administration containing 17 mg alogliptin benzoate equivalent to 12.5 mg alogliptin and any of the following strengths of pioglitazone hydrochloride:

•
16.53 mg pioglitazone hydrochloride equivalent to 15 mg pioglitazone (12.5 mg/15 mg)
33.06 mg pioglitazone hydrochloride equivalent to 30 mg pioglitazone (12.5 mg/30 mg)
•
49.59 mg pioglitazone hydrochloride equivalent to 45 mg pioglitazone (12.5 mg/45 mg)
OSENI tablets contain the following inactive ingredients: mannitol, microcrystalline cellulose, hydroxypropyl cellulose, croscarmellose sodium, magnesium stearate and lactose monohydrate; the tablets are film-coated with hypromellose, polyethylene glycol, titanium dioxide, talc and ferric oxide (yellow and/or red) and are marked with printing ink (Red A1 or Gray F1).

12 CLINICAL PHARMACOLOGY12.1 Mechanism of Action
12.1 Mechanism of ActionOSENI combines two antihyperglycemic agents with complementary and distinct mechanisms of action to improve glycemic control in patients with type 2 diabetes: alogliptin, a selective inhibitor of DPP-4, and pioglitazone, a member of the TZD class.

Alogliptin

Increased concentrations of the incretin hormones such as glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) are released into the bloodstream from the small intestine in response to meals. These hormones cause insulin release from the pancreatic beta cells in a glucose-dependent manner but are inactivated by the DPP-4 enzyme within minutes. GLP-1 also lowers glucagon secretion from pancreatic alpha cells, reducing hepatic glucose production. In patients with type 2 diabetes, concentrations of GLP-1 are reduced but the insulin response to GLP-1 is preserved. Alogliptin is a DPP-4 inhibitor that slow