286. Mechanism of action of hypoglycaemic drugs

Question 1

List the classes of hypoglycaemic drugs (5)

Answer 1

Biguanides
Sulphonylureas
Thiazolidinediones
Incretin mimetic and DDP-4 inhibitors
SGLT2 inhibitors

Question 2

Describe the mechanism of action of sulphonylureas

Answer 2

Inhibits ATP-sensitive K+ channels, closing them
This leads to depolarisation as K+ cannot leave the cell
Ca+ influx into the beta cell as a result which leads to exocytosis of insulin

Question 3

Name examples of sulphonylureas

Answer 3

Gliclazide
Glimepiride
Tolbutamide
Glipizide
Glibenclamide

Question 4

Biguanides (metformin) are the most widely prescribed hypoglycaemic drug. What is its mechanism of action?

Answer 4

Mimics insulin by inhibiting hepatic gluconeogenesis
- inhibits G6Pase and PEPCK
Mechanism of action is uncertain but all involve inhibition of liver mitochondrial function

Question 5

What is the mechanism of action of thiazolidinediones and which one is still used?

Answer 5

Stops inappropriate deposition of lipid in non-adipose tissues (which leads to insulin resistance) - therefore improves insulin sensitivity

Pioglitazone still used

Question 6

What are incretins and name 2 of them. What enzyme inactivates these?

Answer 6

Gastrointestinal hormones that potentiate insulin secretion

• glucagon-like peptide-1 (GLP-1)
• Gastric inhibitory peptide (GIP)

Inactivated by dipeptidyl peptidase-4 (DPP-4)

Question 7

Name two incretin mimetics, how these are administered and how these improve insulin secretion

Answer 7

Exenatide, liraglutide
Injected
Not cleaved by DDP-4

Question 8

Name two DDP-4 inhibitors, how these are administered and how the increase insulin secretion

Answer 8

Sidagliptin, vildagliptin
Oral drugs
Increase endogenous incretin-mediated increase in insulin secretion

Question 9

Name 3 SGLT2 inhibitors

Answer 9

Canagliflozin
dapagliflozin
empagliflozin

Question 10

What are the mechanisms of action of SGLT2 inhibitors?

Answer 10

Inhibits renal uptake of glucose from filtrate by SGLT2
Reduces hyperglycaemia

Also reduces blood pressure and EMPA-REG and CANVAS trials suggest it reduces cardiovascular mortality and hospitalisation due to cardiovascular events