Description

Composition:

Each uncoated bilayer tablet contains:

Glimepiride USP – 1mg

Pioglitazone Hydrochloride IP

to Pioglitazone 15mg

Metformin Hydrochloride IP- 500mg

(as extended release)

Mechanism:

Glimepiride is an insulin secretagogue and, like other sulfonylureas, is only effective in patients with residual pancreatic beta-cell activity. They act at ATP-dependent potassium channels on the cell membrane of pancreatic beta cells, causing iatrogenic depolarization by preventing potassium from exiting the cell. The depolarization activates voltage-dependent calcium channels on the cell membrane, leading to a rise in intracellular calcium and subsequent exocytosis of insulin into the bloodstream.

The mechanism through which TZDs exert their anti-diabetic effect is augmenting insulin sensitivity by acting on muscle, adipose, and liver tissue. TZDs increase peripheral tissue glucose utilization and, to some extent, decrease glucose production in the liver. This action involves activating a nuclear receptor, the gamma isoform of peroxisome proliferator-activated receptor (PPAR-gamma). The activation of this nuclear receptor, in turn, alters the gene transcription of several genes involved in glucose and lipid metabolism, along with energy balance. Some genes are stimulated, and some genes are inhibited. This includes the genes for fatty acid transporter protein, lipoprotein lipase, glucokinase, and the GLUT4 glucose transporter.

Metformin is a biguanide drug that reduces blood glucose levels by decreasing glucose production in the liver, decreasing intestinal absorption, and increasing insulin sensitivity. Metformin decreases both basal and postprandial blood glucose levels.