Biguanide

Question 1

What drug class is metformin?

Answer 1

Metformin is a biguanide

Question 2

What are the MOAs of metformin?

Answer 2

Reduces hepatic glucose production; increases peripheral utilisation of glucose

Question 3

What are the indications of metformin?

Answer 3

1. Treatment of T2DM
   Accepted:
2. anovulatory infertility due to PCOS

Question 4

What are the precautions with metformin use?

Answer 4

1. Renal
2. Hepatic (avoid in severe hepatic impairment)
3. surgery
4. Elderly
5. Pregnancy

Question 5

Can you use metformin in a patient who is pregnant or breastfeeding?

Answer 5

• pregnancy: usually replaced with insulin, there is some clinical experience & metformin appears safe (h/w long term data is limited)
• breastfeeding: safe to use

Question 6

What are some common adverse effects of metformin?

Answer 6

Nausea 
Vomiting 
Anorexia
Diarrhoea 
Malabsorption of vitamin B12

Question 7

What are some RARE adverse effects of metformin?

Answer 7

Lactic Acidosis

Acute Hepatitis

Question 8

What is the dosing range of metformin in adults using the conventional tablet for T2DM?

Answer 8

Initially 500mg, 1-3 times daily; may be increased up to 850mg, 2-3 times daily according to response.

Max daily dose = 3g

Question 9

What is the maximum daily dose of a conventional metformin tablet for treatment of T2DM?

Answer 9

max daily dose = 3g

Question 10

What is the dosing range of metformin in adults using the controlled release tablet for T2DM?

Answer 10

Initially 500mg once daily; may be increased up to 2g one daily.

Question 11

What is the maximum daily dose of a controlled release metformin tablet for treatment of T2DM?

Answer 11

max 2g daily dose

Question 12

What is the recommendation for dose conversion from conventional to controlled release metformin?

Answer 12

When changing from conventional tablets, start with the patient’s usual daily dose.
(If >2g daily dose required, use conventional tablets)

Question 13

What dose requires changing from CR to conventional tablets?

Answer 13

If >2g daily dose is required, use conventional tablets

Question 14

What is the dosing for metformin in polycystic ovary syndrome?

Answer 14

500 mg 2-3 times daily as tolerated, has been used; may be increased up to 2g daily

Question 15

What is the maximum daily dose of metformin for treatment of polycycstic ovarian syndrome?

Answer 15

Up to 2 grams daily (conventional)

Question 16

What is the dosing regimens for renally-impaired patients?

Answer 16

A reduced maximum adult dose is suggested for patients with stable renal function:

CrCl 60–90 mL/minute, 2 g daily.

CrCl 30–60 mL/minute, 1 g daily.

CrCl 15–30 mL/minute, 500 mg daily.

Question 17

What is the maximum metformin daily dose for patients with a CrCl 60-90mL/min?

Answer 17

Maximum daily dose = 2g

Question 18

What is the maximum metformin daily dose for patients with a CrCl 30-60mL/min?

Answer 18

Maximum daily dose = 1 g

Question 19

What is the maximum metformin daily dose for patients with a CrCl 15-30mL/min?

Answer 19

Maximum daily dose = 500mg

Question 20

What are the counselling points for metformin?

Answer 20

1. Take with food to reduce stomach upset
2. Swallow whole CR tablets - don’t Crush/chew
3. Tell your doctor immediately if you have loss of appetite, N & V, abdominal pain, crapms, fatigue, diarrhoea or weight loss
4. Drinking alcohol can affect control of your diabetes. It can also increase the risk of serious SEs. Limit your alcohol intake, avoid binge drinking and have something to eat when you drink alcohol.

Question 21

What are the practice points for metformin?

Answer 21

1. slow onset of effect; control may take up to 2 wks to establish
2. check renal function before starting treatment and q4-6mths
3. increase dosage slowly to limit GI adverse effects; reduce or stop if symptoms persist.
4. compliance with treatment is most important, so be guided by convenience for the patient when advising when to take the dose of CR metformin; if GI ADR are a problem with mane consider giving with the evening meal

Question 22

What action does metformin provide with polycystic ovarian syndrome and fertility?

Answer 22

Pre-treatment with metformin may reduce the risk of ovarian hyperstimulation syndrome in women with PCOS undergoing IVF

Question 23

How long does it take for metformin to start working?

Answer 23

Metformin has a slow onset of effect; control may take up to 2 weeks to establish

Question 24

How often should a person’s renal function be monitored when using metformin?

Answer 24

Baseline then every 4-6 months

Question 25

Why is the dose of metformin increased slowly?

Answer 25

Increase dose slowly to minimise GI adverse effects.

Reduce of stop treatment if symptoms persist

Question 26

What is the relationship between metformin and lactic acidosis?

Answer 26

Metformin has rarely been associated with lactic acidosis.

A casual relationship with metformin is not established and epidemiological data suggest that the incidence of lactic acidosis in metformin-treated diabetics is not higher than in patients on other treatments

Question 27

What are the metformin IR and CR product strengths available?

Answer 27

IR: 500mg, 850mg, 1 g
CR: 500mg, 1 g

Question 28

When should metformin be stopped?

Answer 28

Stop metformin if patient becomes acutely unwell and is at risk of further deterioration of renal function

Question 29

What is the recommendation surrounding metformin and surgery?

Answer 29

Stop metformin before surgery; monitor BGL; replace with insulin as required. Restart metformin when patient is no longer fasting and renal function has recovered.

Question 30

What is the precaution with the elderly population and metformin?

Answer 30

Use cautiously.
Check renal function and for adverse effects; reduce dose (or stop treatment) if necessary.

Avoid combination with glibenclamide (the fixed-dose combination is particularly unsuitable as dose titration is difficult).