Antidiabetic drugs

Question 1

1) Name the P drug which is a Biguanide.
2) Give the P drug examples of Sulfonylureas.
3) Name the P drug which is a Meglitinide.

Answer 1

1) Metformin
2) Gliclazide and Glimepiride.
3) Repaglinide

Question 2

1) Name the 2 P drugs which are DPP-4 inhibitors.
2) Name the P drug which is a thiazolidinedione.
3) Name the P drug which is a glucosidase inhibitor.

Answer 2

1) Sitagliptin and Linagliptin
2) Pioglitazone
3) Acarbose

Question 3

1) Name 3 P drugs which are SGLT-2 inhibitors.

2) Name 2 P drugs which are GLP-1 agonists.

Answer 3

1) Empagliflozin, Canagliflozin and Dapagliflozin

2) Liraglutide and Semaglutide

Question 4

Give the main common clinical indication for the use of Metformin.

Answer 4

T2DM as a first choice medication for control of blood glucose, used alone or in combination with other oral hypoglycaemic drugs (sulphonylureas or insulin).

Question 5

1) How does Metformin lower blood glucose?
2) What does Metformin suppress?
3) What does Metformin increase?
4) What does Metformin suppress?

Answer 5

1) By increasing the response (sensitivity) to insulin.
2) It suppresses hepatic glucose production (glycogenolysis and gluconeogenesis).
3) Increases glucose uptake and utilisation by skeletal muscle.
4) It suppresses intestinal glucose absorption.

Question 6

1) Why is hypoglycaemia not a risk factor of Metformin?

2) How can Metformin prevent the worsening of insulin resistance and slow deterioration of DM?

Answer 6

1) Because it does not stimulate pancreatic insulin secretion.
2) By reducing weight gain and inducing weight loss.

Question 7

1) What adverse effect does Metformin commonly cause which can also result in weight loss?
2) What is a rare adverse effect associated with Metformin use?

Answer 7

1) GI upset (nausea, vomiting, taste disturbance, anorexia and diarrhoea).
2) Lactic acidosis which can be fatal if untreated (does not occur in stable patients).

Question 8

Name 3 things which can precipitate lactic acidosis with Metformin use?

Answer 8

1) Intercurrent illness which causes Metformin accumulation (for example, worsening renal impairment).
2) Increased lactate production (sepsis, hypoxia, cardiac failure).
3) Reduced lactate metabolism (liver failure).

Question 9

1) How is Metformin excreted?
2) When is Metformin contraindicated and when is a dose reduction required?
3) When should Metformin be withheld?

Answer 9

1) Unchanged by the kidney.
2) Contraindicated in severe renal impairment and a dose reduction is required for patients with moderate renal impairment.
3) When there is AKI (sepsis/ shock/ dehydration) or severe tissue hypoxia (cardiac or respiratory failure/ MI).

Question 10

1) Why is caution with the use of Metformin required in hepatic impairment?
2) Why should Metformin be withheld during acute alcohol intoxication?
3) Why should Metformin be used with caution in chronic alcohol overuse?

Answer 10

1) Because clearance of excess lactate may be impaired.
2) Because in acute alcohol intoxication it can precipitate lactic acidosis.
3) Because there is a risk of hypoglycaemia.

Question 11

1) Why must Metformin be withheld before and for 48 hours after injection of IV contrast media?
2) What other drugs need to be used with caution in combination with Metformin and why?
3) Name 3 drugs which elevate blood glucose and therefore reduce the efficacy of Metformin.

Answer 11

1) Because there is an increased risk of renal impairment, metformin accumulation and lactic acidosis.
2) Drugs such as ACEi’s, NSAIDs and diuretics which have potential to impair renal function, especially when used in combination with Metformin (ensure to monitor renal function).
3) Prednisolone, thiazides and loop diuretics as they oppose the actions and reduce efficacy of Metformin.

Question 12

1) How is Metformin available for administration?
2) Why should Metformin be started at a low dose and increased gradually?
3) Describe the common regimen for the commencement of Metformin.

Answer 12

1) Available for oral administration.
2) Because this way, GI adverse effects of Metformin are better tolerated.
3) Common regimen = start Metformin 500mg OD with breakfast, then increase dose by 500mg weekly to 500-850mg TDS with meals.

Question 13

1) Give 2 reasons as to why Metformin would be stopped.
2) If patients find GI side effects difficult to tolerate, what could be done to help?
3) For safety, what must you do before starting Metformin?

Answer 13

1) If adverse effects are intolerable or if new contraindications develop.
2) Changing from a standard to a modified-release preparation may help.
3) Measure renal function before starting treatment, and then measure at least annually.

Question 14

1) When might renal function need to be measured more frequently?
2) How long should conservative treatment be tried for for T2DM before introducing drug therapy?
3) Why is Metformin usually the first choice of drug treatment in T2DM unless contraindicated?

Answer 14

1) In people with deteriorating renal function or an increased risk of renal impairment (needs to be measured at least twice annually).
2) For 3 months.
3) Because it does not cause weight gain where as insulin and drugs which increase insulin secretion cause weight gain which can worsen DM over the long term.

Question 15

Give the main common clinical indication for the use of Sulphonylureas.

Answer 15

Used in T2DM as a single agent to control blood glucose and reduce complications where metformin is contraindicated or not tolerated.

Can also be used in combination with Metformin (and/ or other hypoglycaemic agents) where blood glucose is not adequately controlled on a single agent.

Question 16

1) How do sulphonylureas lower blood glucose?
2) What do sulphonylureas block and what does this cause?
3) What causes the stimulation of insulin secretion with sulphonyl ureas?

Answer 16

1) By stimulating pancreatic insulin secretion.
2) They block ATP-dependent K+ channels in pancreatic beta-cell membranes, causing depolarisation of the cell membrane and opening voltage-gated Ca2+ channels.
3) Increases in intracellular Ca2+ concentrations stimulate insulin secretion.

Question 17

1) Sulphonylureas are only effective in which types of patients?
2) Why is stimulation of insulin by sulphonylureas associated with weight gain?
3) What is a negative effect of weight gain caused by sulphonylureas?

Answer 17

1) They are only effective in patients with residual pancreatic function.
2) Because insulin is an anabolic hormone.
3) Weight gain increases insulin resistance and can worsen DM in the long-term.

Question 18

Describe the dose related side effects of Sulphonylureas.

Answer 18

GI upset: nausea, vomiting, diarrhoea, constipation - these are usually mild and infrequent.

Question 19

1) Name a potentially serious adverse effect of sulphonylureas.
2) When might this potentially serious side effect be more likely?
3) How long might sulphonylurea-induced hypoglycaemia last for?

Answer 19

1) Hypoglycaemia.
2) More likely with high treatment doses, in cases where drug metabolism is reduced or where other hypoglycaemic medications are prescribed.
3) Can last for hours, and if severe, should be managed in hospital.

Question 20

Name 3 rare hypersensitivity reactions which can occur with use of sulphonylureas.

Answer 20

1) Hepatic toxicity (e.g. cholestatic jaundice)
2) Drug hypersensitivity syndrome (rash, fever and internal organ involvement).
3) Haematological abnormalities (e.g. agranulocytosis)

Question 21

1) Where is gliclazide metabolised?
2) How is gliclazide excreted?
3) When might a dose reduction of sulphonylureas be required?
4) When might you need to monitor blood glucose levels carefully in a patient taking sulphonylureas?

Answer 21

1) Metabolised in the liver (half-life of 10-12 hours)
2) Unchanged drug and metabolites are excreted in the urine.
3) In those with hepatic impairment.
4) In those with renal impairment as this might cause a slower level of excretion (risk of hypoglycaemia).

Question 22

When should sulphonylureas be prescribed with caution?

Answer 22

In those at an increased risk of hypoglycaemia:

1) hepatic impairment (reduced gluconeogenesis)
2) malnutrition
3) adrenal or pituitary insufficiency (lack of counter-regulatory hormones)
4) in the elderly.

Question 23

1) When is the risk of hypoglycaemia increased in patients taking Sulphonylureas?
2) When is efficacy of Sulponylureas reduced?

Answer 23

1) When there is co-prescription of other anti diabetic drugs (Metformin, Thiazolidinediones - Pioglitazone and insulin).
2) Efficacy is reduced by drugs that elevate blood glucose (e.g. Prednisolone, thiazide and loop diuretics).

Question 24

1) Which types of sulphonylureas are easiest to use?
2) How are sulphonylureas administered?
3) At what times of day should sulphonylureas be taken?

Answer 24

1) Those with a shorter duration of action and hepatic metabolism (e.g. gliclazide) - particularly in the elderly with impaired renal function.
2) Oral administration only.
3) With meals.

Question 25

Why might it be useful to measure renal and hepatic function before treatment?

Answer 25

In order to determine if there is any need for caution or to identify contraindications to treatment.

Question 26

During acute illness, why are all hypoglycaemics less effective at controlling blood glucose and why are side effects more likely?

Answer 26

Because insulin resistance increases and renal and hepatic function may become impaired.

Question 27

In hospital inpatients with severe illness, why might insulin be preferred for control blood glucose levels in comparison with oral hypoglycaemics for a short time?

Answer 27

Because insulin has a short half-life and its dosage can be adjusted more easily than with oral medication in response to acute fluctuations in blood glucose.

Question 28

Give the main common clinical indications for the use of Thiazolidinediones such as Pioglitazone.

Answer 28

In type 2 diabetes:
1) As a single agent in overweight patients where metformin is contraindicated or not tolerated.

2) Added as a second agent to Metformin or sulphonylureas where blood glucose control is inadequate on one drug and the metformin/ sulphonylurea combination is contraindicated or not tolerated.
3) Added as a third agent with Metformin and a sulphonylurea where blood glucose control is inadequate as an alternative to starting insulin.

Question 29

1) What type of drug are Thiazolidinediones?

2) How to Thiazolidinediones lower blood glucose concentrations?

Answer 29

1) Insulin sensitisers.
2) By activating the gamma subclass of nuclear peroxisome proliferator-activated receptors (PPAR-gamma). This induces genes which enhance insulin action in skeletal muscle, adipose tissue and the liver, with increased peripheral glucose uptake and utilisation and reduced hepatic gluconeogenesis.

Question 30

1) Why is hypoglycaemia not a risk with Thiazolidinediones?

2) Do thiazolidinediones cause weight gain or weight loss?

Answer 30

1) Because they do not stimulate pancreatic insulin secretion.
2) They cause weight gain which can increase insulin resistance.

Question 31

Give 3 more common adverse effects of Pioglitazone.

Answer 31

1) GI upset
2) Anaemia
3) Minor neurological effects (dizziness, headache and disturbed vision).

Question 32

1) Name 2 more serious side effects of Pioglitazone.
2) When might these more serious side effects be more likely to occur?
3) There is a small increased risk of what side effect of Pioglitazone, specifically in women?
4) Pioglitazone is associated with a small increased risk of which malignancy?

Answer 32

1) Oedema and cardiac failure.
2) When Pioglitazone is prescribed with insulin.
3) Bone fractures.
4) Bladder cancer.

Question 33

1) Name an idiosyncratic reaction of Pioglitazone.
2) Why was the license for the thiazolidinedione ‘Rosiglitazone’ suspended?
3) Why was Troglitazone withdrawn from the pharmaceutical market?

Answer 33

1) Severe liver toxicity.
2) Because cardiovascular risk associated with this drug appears greater than its potential benefits.
3) Due to liver toxicity.

Question 34

Give 2 contraindications to the use of Pioglitazone.

Answer 34

It is contraindicated in people with heart failure and in patients with bladder cancer or macroscopic haematuria.

Question 35

Give 2 situations when Pioglitazone should be used with caution.

Answer 35

In patients with CVD and in patients with risk factors for bladder cancer (smoking, occupational exposure, prior pelvic irradiation).

Question 36

1) Why is careful consideration needed when prescribing Pioglitazone for the elderly?
2) Why should Pioglitazone be used with caution in patient’s with hepatic impairment?

Answer 36

1) Because they tend to have increased risk of cardiac disease, bladder cancer and bone fractures.
2) Because Pioglitazone is extensively metabolised in the liver and can cause liver toxicity.

Question 37

Describe the only potential drug interaction of Pioglitazone.

Answer 37

When it is prescribed in combination with other anti-diabetic drugs, this increases the risk of adverse events such as hypoglycaemia and cardiac failure.

Question 38

1) How is Pioglitazone available for administration?
2) When should Pioglitazone tablets be taken?
3) What should be measured prior to starting Pioglitazone for safety?

Answer 38

1) Available orally.
2) Should be taken in the morning with a glass of water.
3) Liver enzymes. Treatment should not be started if baseline transaminase levels are increased and may need to be discontinued if values are persistently elevated during treatment.

Question 39

1) Name 2 newer classes of anti diabetic drugs.
2) What do these new classes of drug do?
3) What do GLP-1 agonists do in particular?
4) Describe the place of these drugs in anti-diabetic therapy.

Answer 39

1) DPP-4 inhibitors (sitagliptin) and GLP-1 agonists (exenatide).
2) Reduce blood glucose by increasing insulin and inhibiting glucagon secretion.
3) They slow gastric emptying.
4) They have a similar place as Thiazolidinediones and can be used as an alternative to these, particularly in obese patients, as they promote weight loss.