Antidiabetics - Biguanides

Question 1

What is gluconeogenesis?

1 - catabolic process of extracting energy from glucose
2 - anabolic process where glucose is produced from non-carbohydrate sources
3 - anabolic process where glucose is added to make glycogen
4 - catabolic process where lipids are broken down to form free fatty acids

Answer 1

2 - anabolic process where glucose is produced from non-carbohydrate sources

• increased during starvation
• no insulin = hyperglycaemia and gluconeogenesis is increased

Question 2

What is the core Biguanides that we need to be aware of?

1 - Gliclazide
2 - Metformin
3 - Dapagliflozin
4 - Linagliptin

Answer 2

2 - Metformin

Question 3

Is metformin the 1st line treatment for patients with T2DM who have not responded to lifestyle changes in an attempt to control their HbA1c?

Answer 3

• yes
• can also be used as dual or triple therapy in patients with poorly controlled HbA1c

Question 4

Metformin is one of the core Biguanide that we need to know. Metformin has a variety of mechanisms. What affect does metformin have on AMPK in the liver, a protein kinase that is important for cellular energy homeostasis, largely to activate glucose and fatty acid uptake and oxidation when cellular energy is low?

1 - increases gluconeogenesis levels to ensure continues supply of glucose
2 - inhibits gluconeogenesis in skeletal muscle
3 - increases AMPK activity and inhibits gluconeogenesis in the liver, reducing blood glucose
4 - accentuates gluconeogenesis and thus increase blood glucose levels

Answer 4

3 - increases AMPK activity and inhibits gluconeogenesis in the liver, reducing blood glucose

• essentially down regulates genes involved in gluconeogenesis
• lower levels of gluconeogenesis mean lower glucose released into the blood by the liver

Question 5

Does metformin increase or decrease glycogenolysis?

Answer 5

• decreases
• catabolic process of glycogen to glucose
• essentially reduces hepatic glucose production

Question 6

Metformin is one of the core Biguanide that we need to know. Metformin has a variety of mechanisms. What affect does metformin have on AMPK in the adipose tissue and skeletal muscle, a protein kinase that is important for cellular energy homeostasis, largely to activate glucose and fatty acid uptake and oxidation when cellular energy is low?

1 - increases number of GLUT-3 receptors on plasma membranes
2 - signals GLUT-4 to desensitise to insulin
3 - signals GLUT-4 in adipose and skeletal muscle to move to plasma membrane
4 - increases insulin receptors in the brain and liver

Answer 6

3 - signals GLUT-4 in adipose and skeletal muscle to move to plasma membrane

Question 7

Incretins are a group of hormones responsible for reducing blood glucose, such as glucagon like peptide-1 (GLP-1). Enteroendocrine cells are specialised cells that are able to release incretins. Do biguanides, specifically metformin increase or decrease GLP-1 release?

Answer 7

• increase the secretion of GLP-1
• GLP-1 binds to GLP GPCR on pancreas and releases insulin in a glucose dependent manner

Question 8

Do biguanides, such as metformin increase or decrease the synthesis of glucose, lipids and protein?

Answer 8

• inhibit the synthesis of glucose, lipids and protein
• stimulate the uptake of glucose and fatty acid oxidation (using fat to produce energy)

Question 9

Biguanides, commonly known as metformin has what effect on lipogenic (converting fatty acids and glycerol into TAG) enzymes and fatty acid oxidation?

1 - inhibits lipogenic enzymes and increased fatty acid oxidation
2 - inhibits lipogenic enzymes and fatty acid oxidation
3 - increases lipogenic enzymes and fatty acid oxidation
4 - increases lipogenic enzymes and inhibits fatty acid oxidation

Answer 9

1 - inhibits lipogenic enzymes and increased fatty acid oxidation

• lipogenic enzyme inhibition means FFA are not stored as fat
• increase fatty acid oxidation means fat is used as an energy source

Question 10

What % of patients taking metformin experience what GI symptoms such as nausea, vomiting and taste disturbance?

1 - 0.5%
2 - 5%
3 - 15%
4 - 25%

Answer 10

2 - 5%

Question 11

Does metformin typically cause hypoglycaemia?

Answer 11

• no
• does not increase insulin secretion from pancreas

Question 12

Gastrointestinal is potentially the most common side effect of metformin. All of the following are side effects, EXCEPT which one?

1 - headaches
2 - B12 deficiency (reduced absorption)
3 - weight loss/anorexia
4 - lactic acidosis
5 - hypoglycaemia

Answer 12

5 - hypoglycaemia

• B12 deficiency is due to GIT symptoms causing reduced absorption

Question 13

Where is metformin removed from the body?

1 - in tissues
2 - liver
3 - kidneys
4 - urine

Answer 13

3 - kidneys

Question 14

Which of the following is NOT a situation where metformin can be prescribed, but caution should be used?

1 - renal impairment
2 - acute kidney injury
3 - hepatic impairment
4 - chronic alcohol abuse

Answer 14

2 - acute kidney injury

Question 15

Metformin should not be prescribed in all of the following EXCEPT which one?

1 - severe tissue hypoxia
2 - acute kidney injury
3 - hepatic impairment
4 - acute alcohol intoxication

Answer 15

3 - hepatic impairment
- can be used but wit caution
- other things it should not be used

Question 16

How can metformin cause lactic acidosis?

1 - increases lactate production in muscles
2 - alters pH of blood leading to lactic acidosis
3 - reduces gluconeogenesis which uses lactic acid
4 - increases enzymes responsible for lactate production

Answer 16

3 - reduces gluconeogenesis which uses lactic acid

• lactate can be recycled in liver during gluconeogenesis to make energy
• metformin inhibits gluconeogenesis meaning lactate remains in the blood
• kidneys can remove lactate, but patient with diabetes have impaired eGFR meaning lactate cannot be effectively removed

Question 17

Biguanides, commonly known as metformin is able to inhibit lipogenic enzymes (storage of FFA and glycerol as TAG) and increase fatty acid oxidation as an energy source. Taking into account this mechanism, what is metformin able to do that other drugs do not do, and part of the reason why metformin is the 1st line drug?

1 - increases beta cell mass
2 - causes weight loss
3 - causes beta cell hypertrophy
4 - reduces glucagon secretion

Answer 17

2 - causes weight loss

Question 18

Some drugs can raise blood glucose, such as prednisolone, thiazide and loop diuretics. What effect can this have on the efficacy of metformin?

Answer 18

• dampens the efficacy
• drug is not as effective

Question 19

How is metformin typically administered?

1 - orally
2 - IV
3 - MI
4 - SI

Answer 19

1 - orally

Question 20

Metformin should prescribed at a lower dose and then titrated up to reduce GI symptoms. What is the standard dose of metformin?

1 - 100mg OD
2 - 250mg OD
3 - 500mg OD
4 - 1g BD

Answer 20

3 - 500mg OD

• should be taken with a glass of water before ot after meals to reduce GI effects

Question 21

The typical target for HbA1c is 48 mmol/mol. However, if a patients HbA1c is still uncontrolled and >58 mmol/mol, what is typically the target?

1 - <44 mmol/mol
2 - <48mmol/mol
3 - <53mmol/mol
4 - <58mmol/mol

Answer 21

3 - <53mmol/mol