Diabetes Mellitus: GLP-1 & The New Drugs

Question 1

How does GLP-1 (Incretin) works in normal physiology?

Answer 1

Question 2

In T2DM patients, what has happened to their Incretin (GLP-1)?

Answer 2

They don’t produce as much and thus lose regulation over their sugar & insulin levels.

Question 3

Describe 2 new drugs that affect Incretin (GLP-1).

Answer 3

1. GLP-1 mimetics - GLP-1 is produced by an oral carbohydrate bolus. It increase the levels of GLP-1 in the body and thus the body is able to better regulate insulin and sugar. (e.g. Exenatide)
2. DPP-4 Inhibitors - GLP-1 does not last for long because it is broken down by DPP-4 enzyme. These DPP-4 inhibitors stop the degradation of GLP-1. (e.g. Gliptins)

Question 4

What is one of the major advantages of GLP-1 mimetics (Exenatide) over other treatments?

Answer 4

It typically results in weight loss whilst medciations like insulin, sulfonylureas(e.g. gliclazide) and thiazolidinediones (e.g. glitazones) can result in weight gain.

Question 5

How must exenatide be given?

Answer 5

It must be given by subcutaneous injection within 60 minutes before the morning and evening meals and should not be given after meals.

Question 6

Exenatide is the name of one GLP-1 mimetic. What is a name for another?

Answer 6

Liraglutide

Question 7

What is an advantage of liraglutide over exenatide?

Answer 7

It only needs to be given once daily whilst exenatide is given twice daily.

Question 8

When does NICE suggest that we add exenatide to metformin and a sulfonylurea?

Answer 8

1. BMI >= 35 kg/m² in people of European descent and there are problems associated with high weight
2. BMI < 35 kg/m² and insulin is unacceptable because of occupational implications or weight loss would benefit other comorbidities.

Question 9

In order to justify the use of GLP-1 mimetics, what does NICE expect to see after 6 months of use?

Answer 9

A 1% reduction in HbA1C and a 3% weight loss.

Question 10

What are the main side effects of exanetide?

Answer 10

• N&V (main one)
• Severe Pancreatitis

Question 11

How are DPP-4 inhibitors taken?

Answer 11

Orally

Question 12

Do DPP-4 inhibitors cause weight gain/

Answer 12

No

Question 13

Name some DPP-4 inhibitors.

Answer 13

Vildagliptin

Sitagliptin

Question 14

Do DPP-4 (Vidagliptin, sitagliptin) inhibitors cause hypoglycaemia?

Answer 14

No

Question 15

What are NICE’s guidelines regarding DPP-4 inhibitors?

Answer 15

• Continue DPP-4 inhibitor only if there is a reduction of > 0.5 percentage points in HBA1c in 6 months
• NICE suggest that a DPP-4 inhibitor might be preferable to a thiazolidinedione if:
  
  • Further weight gain would cause significant problems
  • A thiazolidinedione is contraindicated
  • The person has had a poor response to a thiazolidinedione