drug notes: metformin

Question 1

what class of drugs is metformin?

Answer 1

biguamide

Question 2

what are some examples of biguamides?

Answer 2

• metformin
• phenformin (which has been withdrawn due to toxicity)
• buformin (which has been withdrawn due to toxicity)

Question 3

how does metformin work?

Answer 3

• it binds and inhibits complex 1 (first enzyme in resp chain) of the mitochondrial respiratory chain
• this causes a fall in cellular ATP
• this causes rise in AMP which activates AMP kinase (which decreases production of glucose)
• it also causes a reduction in gluconeogenesis
• increases insulin sensitivity

Question 4

is metformin hydrophobic or hydrophilic?

Answer 4

hydrophilic

Question 5

how is metformin taken up by cells?

Answer 5

• due to being hydrophilic metformin is not readily taken up by cells
• it requires active transport by Organic Cation Transporters (OCTs) which are present in intestines, liver and kidneys

Question 6

what is main role of metformin in the gut?

Answer 6

increases gut glucose utilization and metabolism

Question 7

what is the main role of metformin in the liver?

Answer 7

lowers hepatic glucose production (in patients with poorly controlled diabetes)

Question 8

what are side effects to metformin?

Answer 8

1/5 have GI intolerance:

• diarrhoea
• bloating
• abdominal pain
• dyspepsia

Weight loss
CV benefit
Metformin associated lactic acidosis (MALA)

Question 9

what is done to reduce metformin side effects?

Answer 9

start it slow

initial 500mg daily for one week then increase by 500mg daily once per week

Question 10

what can be done if patient is not reacting well to metformin when started slowly?

Answer 10

could use the modified release formula which means it would release more slowly

Metformin M/R 1g once a day or 2g once a day

Question 11

what effect does metformin have on lactate production?

Answer 11

it increases lactate production especially by gut and liver

Question 12

what normally clears lactate?

Answer 12

-liver and kidneys

Question 13

what injury is associated with increased risk of metformin associated lactic acidosis?

Answer 13

acute kidney injury as kidneys usually clear the lactate

Question 14

what should be done to metformin dose if renal function falls?

Answer 14

it should be decreased

max dose 1g daily if eGFR <45ml/min
contraindicated if eGFR <30ml/min

Question 15

what is first line therapy for type 2 diabetes?

Answer 15

metformin and lifestyle change