Oral antidiabetics

Question 1

How do Sulfonylureas work?

Answer 1

Increase insulin secretion from the pancreas

Question 2

Which are short acting and which are long acting sulfonylureas? (5)

Answer 2

Short acting:

Gliclazide
Glipizide
Tolbutamide

Longer acting:
Glimepramide
Glibenclamide (longest acting)

Question 3

Which sulfonyurea is most prone to causing Hypoglyceamia, and therefore should be avoided in which population group?

Answer 3

Glibencamide (longest acting)

Avoid use in the elderly

Question 4

How should sulfonylurea induce Hypoglyceamia be treated?

Answer 4

Hypoglyceamia can persist for many hours.
It must always be treated in hospital

NB: Hypoglyceamia with sulfonylureas is uncommon and usually indicates excessive dosage

Question 5

When in the T2 diabetes treatment guidelines is a sulfonylurea indicated?

Answer 5

After diet/ lifestyle, then metformin alone have been tried:

Can use a sulfonylurea instead if metformin Contra-indicated, patient is NOT overweight or rapid response is needed as glucose levels very high.

If metformin alone does not work, can then add in a sulfonylurea

Question 6

What side effects can sulphonylureas cause? (4)

Answer 6

Weight gain

GI disturbance: Diarrhoea, constipation, nausea, vomitting

Fever (usually in first 6- 8 weeks)

Jaundice (avoid in severe liver impairment)

Question 7

What is Metformins Mechanism of Action?

Answer 7

It is a Biguanide:

Decreases gluconeogenesis (production of new glucose) and increases peripheral utilisation of glucose

Remember: metformin produce normoglyceamia rather than hypoglyceamia

NB: It does not increase insulin secretion like other oral antidiabetics, therefore it does not cause weight gain!

Question 8

Main side effects of Metformin? (3)

Answer 8

GI upset- take with food, use MR if intolerable

Weight loss

Taste disturbance

Question 9

Metformin can cause Lactic Acidosis. What would be potential risk factors for this?

Answer 9

risk factors such as

renal dysfunction (as metformin accumulates),

liver disease,

heavy alcohol ingestion

IV contrast media- reduces renal function therefore lactic acidosis risk

Poor tissue perfusion/ poor renal function= risk of lactic acidosis

Question 10

What vitamin can Metformin cause deficiency in?

Answer 10

Vitamin B12

Can lead to vitamin B12 deficient aneamia: symptoms= increased tirednes, weakness, mouth ulcers, pins and needles

Question 11

When does metformin become contra-indicated in renal impairment?

Answer 11

In severe renal impairment

eGFR falls below 30 ml/min/ 1.73m2

In moderate impairment (eGFR under 45) a dose reduction is needed

Question 12

Max dose of metformin?

Answer 12

2g a day

Question 13

What is Acarbose and what is its mechanism?

Answer 13

Alpha glucosidase inhibitor- (remember Alpha= Acarb) this enzyme breaks down starch and disaccharides to glucose, so Acarbose stops this, thereby delaying the digestion and absorption of starch and sucrose- small but significant effect in loweing blood glucose.

Acarbose= Starchy effects (potatoes!)

Question 14

What are the common Side effects of acarbose?

Answer 14

FLATULENCE- advise this will decrease with time

Diarrhoea/ Soft stools (as poo becomes sugary due to limited glucose absorption)

Other GI effects

Question 15

How should patients be advised to take Acarbose?

Answer 15

Chew with first moutful of food or swallow with a little liquid immediately before food.

Question 16

What happens if a patient on metformin is injected with Iodine X-ray contrast media?

Answer 16

Interaction:

Renal function deteriorates rapidly

can then increase risk of Lactic acidosis

Question 17

What enzyme do the Gliptins inhibit?

How does this help lower glucose?

Linagliptin
Sitagliptin
Vildagliptin
Saxagliptin

Answer 17

Inhibit an enzyme called Dipeptidylpeptidase-4

This enzyme breaks down incretins, incretins trigger insulin secretion and lower glucagon secretion, therefore they are good at helping control glucose, so by inhibiting the enzyme that breaks them down, gliptins increase incretin levels.

Gliptins.. incretins… gliptins…. incretins!

Question 18

What are the side effects of the gliptins (dipeptidylpeptidase 4 inhibitors)? (5)

Answer 18

Upper respiratory tract infections

Gatro-intestinal upset

Peripheral oedema

Pancreatitis

Trigger insulin release so some weight gain?

There is less risk of Hypoglyceamia with the gliptins!

Question 19

Which of the gliptins (Dipeptidylpeptidase-4 inhibitors) should patients have their liver function monitored if taking?

Answer 19

Vildagliptin

Report symptoms of liver disease: nausea, vomitting, abdominal pain, fatigue, dark urine

Question 20

Which oral antidiabetics can cause acute pancreatitis?
What are the symptoms of this?

Answer 20

Dipeptidylpeptidase-4 inhibitors (gliptins- sitagliptin, Linagliptin etc)

Glucagon-like peptide-1 receptor agonists (Exenatide, Liraglutide, Lixisenatide)

Exanatide especially can cause SEVERE PANCREATITIS

Symtpoms: Persistent and severe abdominal pain
Nausea and vomitting

Question 21

What is the mechanism of action of the Thiazolidinediones? (Only one licensed in UK is pioglitazone)

Answer 21

Reduces peripheral insulin resistance

Question 22

Which oral antidiabetics must care be taken with in Heart Failure? And what cancer can it possibly increase risk of?

Answer 22

Pioglitazone

Incidence of HF increased when pioglitazone is combined with insulin

Also small risk of BLADDER cancer

Signs of bladder cancer: blood in urine, pain on urination, urinary urgency

Question 23

can oral anti-diabetic drugs cause headaches?

Answer 23

Yes- alot of them cause a headache, particularly pioglitazone and the gliptins

Question 24

How do the Meglitinides work?
Can you name them?

When should they be taken?

Answer 24

Nateglinide
Repaglinide

Stimulate insulin secretion

Take 30 minutes before meals

Question 25

Can you name any oral anti-diabetic drugs that can cause liver toxicity?

Answer 25

Pioglitazone

The Gliptins- linagliptin, sitagliptin, vildagliptin

Question 26

What are GLP-1 agonists? How do they work?

Answer 26

Glucagon-like peptide-1 receptor agonists

Examples:
Exenatide
Liraglutide
Lixisenatide

These are given by SUBCUTANEOUS INJECTION- not oral

These work by binding to the GLP-1 receptor causing:

• > Increase in insulin secretion
• > suppression of glucagon secretion (glucagon gets converted in glucose usually)
• > Slow gastric emptying

If given with sulfonylureas or insulin, their dose may need to be reduced as increased risk of hypoglyceamia!

Question 27

What drug do we have to be particularly vigelant for symptoms such as persistent and severe abdominal pain, nausea and vomitting?

Answer 27

Exenatide (GLP-1 agonist)

These are symptoms of pancreatitis- exanatide can cause severe pancreatitis- discontinue permanently

Question 28

What should patients be advised to do if they miss a dose of Exenatide? How should it usually be administered?

Answer 28

Miss that dose out and just continue with the next scheduled dose.

Usual dose is to be injected 1 hour before 2 main meals a day that are at least 6 hours apart

Do not administer the dose after a meal

Some oral med’s need to be given 1 hour before or 4 hours after this drug

Question 29

What are the SGLT2 inhibitors?

3 examples?

How do they work?

Answer 29

Sodium Glucose Co-transporter 2 inhibitors

Gliflozins

Examples:
Canagliflozin
Dapagliflozin
Empagliflozin

(DECeeeee!)

The sodium glucose transporter is found in the kidneys: by inhibiting this they stop glucose be re-absorbed in the renal tubule and therefore more glucose is excreted

Question 30

What important Side effect can the SGLT2 inhibitors (Canagliflozin, dapagliflozin, empagliflozin) cause?
What concomitant drugs/ conditions could increase the risk of this?

Answer 30

Volume depletion !

Think floz= flow

Think: these are inhibiting glucose rer-absorption into the renal tubules. Water usually follows the glucose- less reabsorbed= less water follows= more weeing etc

Patients need to report signs of this:
Dizzy, postural hypotension
Side effects:
Thirst
Constipation (less water in stools)
UTI’s

Increased risk: things that also decrease fluid volume

Antihypertensives
Elderly
diarrhoea

Question 31

Sitagliptin and Vildagliptin, dipeptidyl peptidase enzyme inhibtior enhancing incretin hormone, should only be continued if HbA1c has been reduced by at least ___ percentage points within 6 months of starting treatment

Answer 31

0.5 percentage points

Question 32

Which class of oral anti-diabetics can increase the risk of Genital infections- Thrush and UTI’s? Name me some of them

Answer 32

The SGLT2 inhibitors:

Dapagliflozin

Canagliflozin

Empagliflozin

Question 33

What condition, other than diabetes, can metformin be used in Unlicensed?

Answer 33

Poylcystic ovary syndrome

It helps to normalise the menstrual cycle an ovulation

Question 34

What are patients on pioglitazone urged to report?

Answer 34

Symptoms of bladder cancer:

heamatruria

dysuria

urinary urgency

Also signs of liver toxicity: blood in urine, severe stomach pain/ nausea and vomiting

Question 35

When should sulfonylureas be taken?

Answer 35

WITH MEALS

Question 36

Patient with hepatic impairment prescribed a sulfonylurea?

Answer 36

Reduce the dose- sulfonylureas metabolised hepatically- they will accumulate and cause hypoglyceamia

Question 37

How should Acarbose be taken?

Answer 37

Chewed with first mouthful of food/ with a bit of water immediately before food

Question 38

What is the name of the thiazide diuretic that can be chronic intractable hypoglyceamia in Neonates/ children?

Answer 38

Diazoxide

(remember diuretics can cause hyperglyceamia)

Question 39

You have a patient suffering from newly diagnosed T2 diabetes with poor renal function, What would be your first line choice of antidiabetic?

Answer 39

A sulfonylurea- Gliclazide

Question 40

If a patient is of European Descent and they have a BMI of over 35, and metformin and gliclazide have failed to control their BG, what agent would you consider next?

Answer 40

Exenatide

This is a NICE recommendation