Diabetes Flashcards
List the various classes of drug used to treat type 2 diabetes, and give an example of each
- Metformin (biguanide)
- Sulphonylureas - e.g. Gliclazide
- Thiazolineinediones - e.g. Pioglitazone
- Meglitidines - e.g. Repaglinide
- DPP4 inhibitors (Gliptins) - e.g. Sitagliptin
- GLP1 analogues - e.g. Exanetide
- SGLT2 inhibitors - e.g. Dapagliflozin
Outline the NICE guidelines on type 2 diabetes management (6 stages)
1) Diet and lifestyle
2) Metformin
3) Metformin + sulphonylurea
4) Metformin + sulphonylurea + either pioglitazone or DPP4 inhibitor
5) Consider other drugs such as GLP1 analogues/SGLT2 inhibitors
6) Insulin
What is the mechanism of action of Metformin?
Increases insulin receptor sensitivity, therefore reducing insulin resistance.
Also inhibits hepatic gluconeogenesis
Does Metformin run the risk of hypoglycaemia?
What about weight gain?
No - doesn’t increase production of insulin
No - associated with reduction in weight gain/weight loss
Name one common and one important ADR associated with metformin
Common - GI upset
Important - lactic acidosis
In whom is Metformin use contraindicated?
Patients with renal failure/severe renal impairment
What sort of drug is Pioglitazone?
Outline its mechanism of action
Thiazolineinedione
Increases insulin sensitivity by binding to and activating one or more peroxisome proliferator-activated receptors - upregulate wide array of proteins which enhance insulin action
They also decrease hepatic gluconeogenesis
Does Pioglitazone cause weight gain? What about hypoglycaemia?
Yes weight gain
No hypoglycaemia
List some common and some severe ADRs of Pioglitazone
Common - GI upset, anaemia, neuro e.g. headache
Serious - cardiac failure and oedema, increased risk of bladder cancer
What class of drug is Gliclazide? Outline its mechanism of action
Sulphonylurea
Acts by inhibiting Beta-cell K+-ATPase channel activity. Therefore K+ acculumulates in the cell, so cell depolarises. This opens voltage-gated calcium channels - increased Ca2+ influx. Therefore increased vesicular fusion - increased insulin release.
Does Gliclazide cause weight gain?
Hypoglycaemia?
Yes to both
List 3 ADRs of Gliclazide
GI upset
Hypoglycaemia
Hypersensitivity (rare)
Outline the theory behind incretin-based therapies (DPP4 inhibitors and GLP1 analogues)
Incretins released from intestine in response to food. One such example is GLP1. Travels to pancreas, where it stimulates Beta cell activity - insulin production.
Therefore increased glucose uptake and reduced gluconeogenesis as relative decrease in glucagon
Therefore can give GLP1 analogues, or DPP4 inhibitors - the latter inhibit enzymes which break down native GLP1
Give an example of a GLP1 analogue
How is it administered?
Exanetide
Injection
Weigh up the advantages and disadvantages of Exanetide
Excellent HbA1c control, promotes weight loss, does not induce hypoglycaemia
BUT very expensive - must be eligible based on various criteria
