Core Drugs Of Diabetes

Question 1

What are 4 drugs used to treat diabetes?

Answer 1

Metformin

Dipeptidyl-peptidase 4 inhibitors (DPP-4) inhibitors

Sulphonylurea

Sodium glucose co-transporter inhibitors (SGLT2 inhibitors)

Question 2

What is the mechanism of action of metformin?

Answer 2

Activates AMPK in hepatocyte mitochondria.

This inhibits ATP production

This blocks gluconeogenesis and subsequent glucose output

It also blocks adenylate Cyclase which promotes fat oxidation (breakdown)

Both of these help to restore insulin sensitivity

Question 3

What is the drug target of metformin?

Answer 3

5’-AMP-activated protein kinase (AMPK)

In the hepatocyte mitochondria

Question 4

What are the main side effects of metformin?

Answer 4

GI side effects in 20-30% of patients - abdominal pain, decreased appetite, diarrhoea, vomiting

Particularly present when high doses are given. Slow increases in dose may increase tolerability

Question 5

What features of Metformin allow it to have its effects?

Answer 5

Highly polar (so can’t cross plasma membranes easily)

Requires organic cation transporter-1 (OCT-1) to access tissues

Explains why it can accumulate in the liver (therapeutic effects) and GI tract (side effects)

Question 6

When is metformin most effective?

Answer 6

In the presence of endogenous insulin.

So when there are still some pancreatic beta islet cells working

Question 7

What is an example of a DPP-4 inhibitor?

Answer 7

Sitagliptin

Question 8

What is the mechanism of action of DPP-4 inhibitors?

Answer 8

Inhibitions the action of DPP-4, an enzyme present in vascular endothelium and can metabolism incretins in the plasma

Incretins (eg. GLP-1) are secreted By enteroendocrine cells and help stimulate the production of insulin when it’s needed (eg. After eating) and reduce the production of glucagon but the liver when it isn’t needed (eg. During digestion)

They also slow down digestion and decrease appetite

Question 9

What is the drug target of DPP-4 inhibitors

Answer 9

DPP-4

On the vascular endothelial

Question 10

What are the main side effects of DPP-4 inhibitors?

Answer 10

Upper respiratory tract infections (5% of patients)

Flu like symptoms (headache, runny nose, sore throat)

Less common: severe allergic reactions
Avoid in patients with pancreatitis

Question 11

What is a pro of metformin and DPP-4 that other diabetes drugs don’t have?

Answer 11

They do not cause weight gain

Question 12

When are DPP-4 Is most effective?

Answer 12

When there are some residual pancreting beta islets functioning and producing insulin

As they augment insulin secretion

Question 13

What is an example of a sulphonylurea

Answer 13

Gliclazide

Question 14

What is the mechanism of action of sulphonylurea?

Answer 14

Inhibits the ATP-sensitive potassium (KATP) channel on the pancreatic beta cell.

This channel controls beta cell membrane potential

Inhibition causes depolarisation which stimulates Ca2+ influx and subsequent insulin vesicle exocytosis

Question 15

What is the drug target of sulphonylurea?

Answer 15

ATP- sensitive potassium channel

In the pancreatic beta cell

Question 16

What are the side effects of sulphonylurea?

Answer 16

Weight gain

Hypoglycaemia

Question 17

When are sulphonylureas most effective?

Answer 17

They augment insulin secretion

So work best when there are still some functioning beta cells

(The weight gain caused by sulphonylurea can be counteracted by giving metformin too)

Question 18

What is an example of an SGLT2 inhibitor?

Answer 18

Dapaflifozin

Question 19

What is the mechanism of action of SGLT2 inhibitors?

Answer 19

Reversibly inhibits sodium glucose co-transporter -2 in the renal Proximal convoluted tubule

This reduces glucose reabsorbtion and increases urinary glucose secretion

Question 20

What is the drug target of SGLT2 inhibitors?

Answer 20

Sodium glucose co-transporter 2

In the proximal convoluted tubules of the kidney

Question 21

What are the side effects of SGLT2 inhibitors?

Answer 21

Uro genital infection due to increased glucose load

Slight decrease in bone formation

Can worsen diabetic ketoacidosis (stop immediately)

They also cause weight loss and a reduction in BP

Question 22

When would SGLT2 inhibitors be less effective?

Answer 22

They rely on normal renal function

So in patients with renal impairment they would be less effective