Diabetes 6

Question 1

What is the mechanism of action of thiazolidinediones (-glitazones) and what is an example of them?

Answer 1

Enhance the effects of insulin in adipose tissue and skeletal muscle, and inhibits hepatic gluconeogenesis.
Pioglitazone.

Question 2

What are the advantages of glitazones?

Answer 2

• Effective in insulin resistant patients
• Reduced risk of hypoglycaemia
• Positive effect on lipids

Question 3

What are the disadvantages of glitazones?

Answer 3

• Inc. risk of heart failure, bladder cancer, renal impairment and weight gain (fluid retention)

Question 4

What monitoring requirements are required for pioglitazone and what serious symptoms need to be looked out for?

Answer 4

Baseline LFTs, every 2 months for a year then periodically.
Symptoms suggesting liver disease: seek medical attention
Jaundice: discontinue treatment

Question 5

What are incretins?

Answer 5

Gastrointestinal hormones released in response to meals to increase insulin secretion.

Question 6

What are the two types of incretins?

Answer 6

GLP-1 (Glucagon like peptide 1), GIP (Glucose dependent insulinotropic peptide)

Question 7

What enzyme rapidly degrades Incretins?

Answer 7

Dipeptidyl peptidase-4 (DPP4)

Question 8

What effect does type 2 diabetes have on incretin levels?

Answer 8

Reduced GLP-1 levels, GIP action is defective/absent

Question 9

What are two examples of DPP4 inhibitors and what are their advantages?

Answer 9

Apogliptin (OD), Vildagliptin (BD)
Weight neutral, well tolerated.

Question 10

How are GLP-1 agonists administered and what are two examples?

Answer 10

Subcutaneous injection.
Liraglutide (once/twice daily), semaglutide (once weekly)

Question 11

What are the side effects of GLP-1 receptor agonists?

Answer 11

Slight weight loss.
Nausea.
Hypoglycaemia with sulfonylureas.

Question 12

What is the first line treatment for type 2 diabetes in patients not at high CVD risk?

Answer 12

Metformin (Initial dose 500mg OD to 500mg after three weeks, inc dose gradually)
- GI disturbance - Metformin MR
- If Metformin contraindicated:
- DPP4 inhibitor or
- Pioglitazone or
- Sulfonylurea or
- SGLT2 inhibitor

Question 13

What is the first line treatment for type 2 diabetes in patients at with ASCVD, heart failure or high risk of CVD?

Answer 13

Metformin/Metformin MR + SGLT2 inhibitor (started as soon as tolerability to Metformin confirmed)
- If metformin contraindicated: SGLT2 inhibitor alone

Question 14

What additional treatment is offered for type 2 diabetes patients whose CVD risk/status changes while on metformin?

Answer 14

Offer an SGLT2 inhibitor (if not already prescribed)

Question 15

What dual therapy treatment is available for type 2 diabetes patients when metformin monotherapy not controlling HbA1c?

Answer 15

Metformin + DPP4 inhibitor/Pioglitazone/sulfonylurea/SGLT2 inhibitor

Question 16

What is an example of triple therapy treatment that is available for type 2 diabetes patients?

Answer 16

Metformin + sulfonylurea + DPP4 inhibitor/SGLT2 inhibitor/Pioglitazone

Question 17

According to NICE guidelines, when are GLP-1 agonists considered to replace a drug for triple therapy?

Answer 17

If previous triple therapy with metformin and two other oral drug not effective/contraindicated/not tolerated
AND BMI ≥ 35 OR BMI <35 and insulin therapy would have significant occupational implications e.g. operating heavy machinery

Question 18

When would you start insulin therapy in type 2 diabetes?

Answer 18

Dual therapy not controlled HbA1c to below agreed threshold
- Metformin continued, other oral medication reviewed and stopped if necessary

Question 19

What three insulin regimens are available for type 2 diabetes?

Answer 19

• Basal insulin at night/BD (human isophane insulin/prolonged action analogues)
• Biphasic insulin injected OD/BD
• Intensive basal Bolus

Question 20

When is blood glucose monitoring required for type 2 diabetes (not on insulin)

Answer 20

Illness, medication changes, patients troubled by hypoglycaemia, to monitor lifestyle changes.
Test twice in one day per week.