Diabetes

Question 1

Name 4 classes of drugs used to treat diabetes

Answer 1

• Metformin
• DPP-4 inhibitors
• Sulphonylureas
• SGLT2 inhibitors

Question 2

Give an example of a DPP-4 inhibitor

Answer 2

Sitagliptin

Question 3

Give an example of a sulphonylurea

Answer 3

Gliclazide

Question 4

Give an example of a SGLT2 inhibitor

Answer 4

Dapagliflozin

Question 5

What does DPP-4 stand for?

Answer 5

Dipeptidyl-peptidase 4

Question 6

What is the primary mechanism

of action for metformin?

Answer 6

• Activates AMPK (5′-AMP-activated protein kinase enzyme) in hepatocyte mitochondria which inhibits ATP gen.
• This blocks gluconeogenesis and adenylate cyclase which promotes fat oxidation so this helps to restore insulin sensitivity

Question 7

What is the primary mechanism

of action for DPP-4 inhibitors?

Answer 7

• Inhibit the action of DPP-4 (enzyme found in vascular endothelium which metabolises incretins in the plasma)
• As incretins e.g. GLP-1 are secreted by enteroendocrine cells and help stim. insulin gen. when it’s needed and reduce glucagon gen. by the liver when it’s not needed (e.g. during digestion), incretins also slow down digestion and decrease appetite

Question 8

What is the primary mechanism

of action for sulphonylureas?

Answer 8

• Inhibit the ATP-sensitive potassium (KATP) channel on pancreatic beta cells
• This channel controls beta cell membrane potential and inhibition causes depolarisation which stim.s Ca2+ influx and insulin vesicle exocytosis

Question 9

What is the primary mechanism

of action for SGLT2 inhibitors?

Answer 9

Reversibly inhibits sodium-glucose co-transporter 2 (SGLT2) in the PCT (so don’t work in renal impairment) to reduce glucose reabsorption and increase urinary glucose excretion

Question 10

What are some side effects of metformin?

Answer 10

• GI side effects - abdo pain, decreased appetite, diarrhoea and vomiting
• Particularly evident when very high doses are given so a slow increase in dose may improve tolerability

Question 11

What are some side effects of DPP-4 inhibitors?

Answer 11

• Upper resp tract infections
• Flu-like symptoms e.g. headache, runny nose and sore throat
• Serious allergic reactions/avoid in patients w/ pancreatitis

Question 12

What are some side effects of sulphonylureas?

Answer 12

• Weight gain - mitigated by concurrent treatment w/ metformin
• Hypoglycaemia

Question 13

What are some side effects of SGLT2 inhibitors?

Answer 13

• Uro-genital infections due to increased glucose load
• Slight decrease in bone formation
• Can worsen DKA (stop immediately)
• Weight loss
• Reduce BP

Question 14

Why would DPP-4 inhibitors not work if there is no endogenous insulin secretion?

Answer 14

DPP-4 inhibitors (and metformin and sulphonylureas) augment insulin secretion as part of their mechanism so otherwise wouldn’t work