Diabetes / Glucose

Question 1

OHAs

Answer 1

Biguanides:

• Metformin decreases hepatic glucose production, GIT glucose absorption, and increases insulin sensitivity (which increases peripheral glu uptake and utilisation)

Sulfonylureas:

• Gliclazide: stimulates insulin release from pancreatic beta cells; reduces insulin uptake and glucose output by the liver; increases insulin sensitivity at peripheral target sites. Also has antithrombotic effects (it also reduces microthrombosis by decreasing platelet aggregation and adhesion, and by restoring fibrinolysis with an increase in tPA activity); and antioxidant effects (decreases plasma levels of peroxidized lipids and increased erythrocyte superoxide dismutase activity).

Thiazolidinediones:

• pioglitazone: improves target cell response to insulin, without increasing pancreatic insulin secretion. It is a potent and selective agonist for peroxisome proliferator-activated receptor-gamma (PPARgamma). Activation of nuclear PPARgamma receptors influences the production of a number of gene products involved in glucose and lipid metabolism. PPARgamma is abundant in the cells within the renal collecting tubules; fluid retention results from stimulation by thiazolidinediones which increases sodium reabsorption.

SGLT2 inhibitors:

• canagliflozin: Inhibits SGLT2 in the PCT, reducing reabsorption of filtered glucose from the tubular lumen and lowers the renal threshold for glucose (RTG). SGLT2 is the main site of filtered glucose reabsorption. Reduction of filtered glucose reabsorption and lowering of RTG result in increased urinary excretion of glucose, thereby reducing plasma glucose concentrations.

GLP-1 (glucagon-like peptide 1) analogues:

• exenatide: increases glucose-dependent insulin secretion, decreases inappropriate glucagon secretion, increases pancreatic beta-cell growth/replication, slows gastric emptying, and decreases food intake. Exenatide administration results in decreases in hemoglobin A1c by approximately 0.5% to 1% (immediate release) or 1.5% to 1.9% (extended release).

Answer 2

Gliclazide