Exam 1 - Biguanides

Question 1

What are the characteristics of the Biguanides?

Answer 1

● Not hypoglycemic agent
● MOA : Decreases hepatic glucose production by INHIBITING GLUCONEOGENESIS: metformin indirectly activates AMP­dependent kinase (AMPK) which is normally activated when cellular energy ATP/AMP ratio is low (i.e.,decreased energy reserves). Activated AMPK is required for the expression of a nuclear protein known as SHP, which in turn can inhibit the expression of hepatic gluconeogenic genes. The ability of metformin to indirectly activate AMPK may result from it ability to inhibit Complex I of the mitochondrial oxidative phosphorylation process thereby decreasing the ATP/AMP ratio
● Increases sensitivity of muscle, adipose to insulin
● Does not stimulate insulin secretion
● Decreases intestinal glucose absorption

Question 2

What are the Biguanide drugs?

Answer 2

Metformin (Glucophage)

Question 3

What are the characteristics of Metformin?

Answer 3

● Can be used in combinations with sulfonylureas, TZD’s, DPP­4 inhibitors, insulin
● Not hypoglycemic agent
● “Gold standard” for Type­2
● Weight Neutral or Loss
● ↑HDL, ↓triglyceride, ↓tot cholest
● “Anti-­hyperglycemic”
Possible lactic acidosis ( don’t use in kidney or liver disease patients, or those with CHF)
● N/V, GI disturbances including ( diarrhea ) → releases 5­HT in gut