T2DM therapeutics

Question 1

Metformin adverse effects

Answer 1

GI side effects:
Anorexia, nausea, vomiting, diarrhoea, abdo pain, taste disturbance
GI side effects in up to 25%; only 5% cannot tolerate the drug

Interference with vitamin B12 and folic acid absorption (anaemia is rare)

Lactic acidosis

    - 1 case per 100,000 treated patients
    - Can be fatal

Liver failure

Rash

Question 2

Lactic acidosis and Metformin

Answer 2

Lactic acidosis:
Rarely causes it de novo, but caution in patients at high pre-existing risk eg acute heart failure, sepsis, acute MI, respiratory failure, hypotension for any cause

Question 3

Metformin and Renal toxicity

Answer 3

Avoid or stop if eGFR 150μmol/l
Half dose if eGFR 30-45 ml/min
Temporarily withhold if IV contrast being used eg. Angiography, CT scan

Question 4

Metformin and liver toxicity

Answer 4

Discontinue if advanced cirrhosis/liver failure
Discontinue if risk of lactic acidosis eg encephalopathy, alcohol excess
May be beneficial in Non-alcoholic fatty liver disease (NAFLD)

Question 5

Gliclazide

Answer 5

Sulphonylurea

40mg od -160mg bd

Question 6

Glibenclamide

Answer 6

Sulphinylurea 5mg - 15mg od

Question 7

Glimepiride

Answer 7

1mg-6mg od

Question 8

Sulphonylurea adverse effects

Answer 8

Hypoglycaemia
Greatest risk with older agents eg chlorpropramide and glibenclamide
Particular care in elderly/frail, alcohol excess, liver disease

Weight gain
Only 1st line use in underweight T2DM, or 2nd line as add-on to metformin, or in those intolerant to metformin

GI upset, headache

Rarely hypersensitivity, blood dyscrasias and liver dysfunction

Avoid in severe renal or hepatic failure

Question 9

Which type of drug might cause hypersensitivty and blood dyscrasias and liver dysfunction?

Answer 9

Sulphonylureas

Question 10

PPARy agonists?

Answer 10

Thiazolidinediones –> pioglitazone 15-45 mg od

Question 11

TZD bad side effects :( </3

Answer 11

RISK OF HIP FRACTURE

Weight Effect: load of shite but interesting
Increase almost inevitable
Due to increase in subcutaneous (but not visceral) fat and fluid retention

Heart Failure
Fluid retention results in near doubling of risk of admission with heart failure (risk still low in non-elderly without pre-existing HF)

Question 12

SGLT2 inhibitor

Answer 12

Dapagliflozin

-acts on the incretin pathway