T2DM Drugs Mechanisms of Action

Question 1

Glucagon-like peptide-1 (GLP-1) agonists

Answer 1

In simple terms:

• GLP1 analogues stimulate insulin secretion and reduce glucagon secretion in a glucose-dependent manner. They also delay gastric emptying and reduce appetite.

In complex terms:

• GLP-1 is secreted by L cells of the small intestine in response to food ingestion. It enhances insulin secretion, suppresses glucagon secretion and slows gastric emptying.
  GLP-1 agonists activate the GLP-1 receptor and causes insulin secretion and subsequent reduction in blood glucose levels.

Question 2

Sulfonylureas

Answer 2

In simple terms:

• Stimulates pancreatic beta-cells, promoting the release of insulin

In more complex terms:

• Stimulate pancreatic beta cells to secrete insulin by binding to the beta cell sulfonylurea receptor. This results in potassium efflux and depolarisation of the cells, which eventually leads to exocytosis of secretory granules containing insulin.

Question 3

SGLT2 (sodium-glucose co-transporter 2) inhibitors

Answer 3

In simple terms:

• Increase urinary glucose excretion, thus reducing blood glucose levels.

In more complex terms:

• Act on sodium-glucose co-transporters in the proximal convoluted tubules of the kidneys to reduce glucose reabsorption and increase urinary glucose excretion.

Another name for SGLT-2 inhibitors is gliflozins, as they all end in the suffix -gliflozin.

Question 4

Pioglitazone (Thiazolidinediones)

Answer 4

In simple terms:

• Act by increasing peripheral insulin sensitivity, thus lowering blood glucose levels.

In more complex terms:

• Reduces peripheral insulin resistance by acting as an agonist to the PPAR-gamma receptor, which controls adipocyte differentiation and function

Question 5

Metformin

Answer 5

Is a Biguanide

In simple terms:

• Works by increasing peripheral insulin sensitivity and enhancing hepatic glucose uptake, thus lowering blood glucose levels.

In more complicated terms:

• Decreases gluconeogenesis and increases peripheral utilisation of glucose. For this reason it is sometimes referred to as an “insulin sensitiser”.

Metformin may also be used in polycystic ovarian syndrome and non-alcoholic fatty liver disease.

Question 6

DPP4-Inhibitors “gliptin”

Answer 6

Work by inhibiting the enzyme DPP4, which breaks down incretin hormones. This leads to an increase in insulin production and a decrease in glucagon release.