How do Sulfonylureas work?
Increase insulin secretion from the pancreas
Which are short acting and which are long acting sulfonylureas? (5)
Glibenclamide (longest acting)
Which sulfonyurea is most prone to causing Hypoglyceamia, and therefore should be avoided in which population group?
Glibencamide (longest acting)
Avoid use in the elderly
How should sulfonylurea induce Hypoglyceamia be treated?
Hypoglyceamia can persist for many hours.
It must always be treated in hospital
NB: Hypoglyceamia with sulfonylureas is uncommon and usually indicates excessive dosage
When in the T2 diabetes treatment guidelines is a sulfonylurea indicated?
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
What side effects can sulphonylureas cause? (4)
GI disturbance: Diarrhoea, constipation, nausea, vomitting
Fever (usually in first 6- 8 weeks)
Jaundice (avoid in severe liver impairment)
What is Metformins Mechanism of Action?
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!
Main side effects of Metformin? (3)
GI upset- take with food, use MR if intolerable
Metformin can cause Lactic Acidosis. What would be potential risk factors for this?
risk factors such as
renal dysfunction (as metformin accumulates),
heavy alcohol ingestion
IV contrast media- reduces renal function therefore lactic acidosis risk
Poor tissue perfusion/ poor renal function= risk of lactic acidosis
What vitamin can Metformin cause deficiency in?
Can lead to vitamin B12 deficient aneamia: symptoms= increased tirednes, weakness, mouth ulcers, pins and needles
When does metformin become contra-indicated in renal impairment?
In severe renal impairment
eGFR falls below 30 ml/min/ 1.73m2
In moderate impairment (eGFR under 45) a dose reduction is needed
Max dose of metformin?
2g a day
What is Acarbose and what is its mechanism?
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!)
What are the common Side effects of acarbose?
FLATULENCE- advise this will decrease with time
Diarrhoea/ Soft stools (as poo becomes sugary due to limited glucose absorption)
Other GI effects
How should patients be advised to take Acarbose?
Chew with first moutful of food or swallow with a little liquid immediately before food.
What happens if a patient on metformin is injected with Iodine X-ray contrast media?
Renal function deteriorates rapidly
can then increase risk of Lactic acidosis
What enzyme do the Gliptins inhibit?
How does this help lower glucose?
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!
What are the side effects of the gliptins (dipeptidylpeptidase 4 inhibitors)? (5)
Upper respiratory tract infections
Trigger insulin release so some weight gain?
There is less risk of Hypoglyceamia with the gliptins!
Which of the gliptins (Dipeptidylpeptidase-4 inhibitors) should patients have their liver function monitored if taking?
Report symptoms of liver disease: nausea, vomitting, abdominal pain, fatigue, dark urine
Which oral antidiabetics can cause acute pancreatitis?
What are the symptoms of this?
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
What is the mechanism of action of the Thiazolidinediones? (Only one licensed in UK is pioglitazone)
Reduces peripheral insulin resistance
Which oral antidiabetics must care be taken with in Heart Failure? And what cancer can it possibly increase risk of?
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
can oral anti-diabetic drugs cause headaches?
Yes- alot of them cause a headache, particularly pioglitazone and the gliptins
How do the Meglitinides work?
Can you name them?
When should they be taken?
Stimulate insulin secretion
Take 30 minutes before meals
Can you name any oral anti-diabetic drugs that can cause liver toxicity?
The Gliptins- linagliptin, sitagliptin, vildagliptin
What are GLP-1 agonists? How do they work?
Glucagon-like peptide-1 receptor agonists
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!
What drug do we have to be particularly vigelant for symptoms such as persistent and severe abdominal pain, nausea and vomitting?
Exenatide (GLP-1 agonist)
These are symptoms of pancreatitis- exanatide can cause severe pancreatitis- discontinue permanently
What should patients be advised to do if they miss a dose of Exenatide? How should it usually be administered?
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
What are the SGLT2 inhibitors?
How do they work?
Sodium Glucose Co-transporter 2 inhibitors
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
What important Side effect can the SGLT2 inhibitors (Canagliflozin, dapagliflozin, empagliflozin) cause?
What concomitant drugs/ conditions could increase the risk of this?
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
Constipation (less water in stools)
Increased risk: things that also decrease fluid volume
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
0.5 percentage points
Which class of oral anti-diabetics can increase the risk of Genital infections- Thrush and UTI's? Name me some of them
The SGLT2 inhibitors:
What condition, other than diabetes, can metformin be used in Unlicensed?
Poylcystic ovary syndrome
It helps to normalise the menstrual cycle an ovulation
What are patients on pioglitazone urged to report?
Symptoms of bladder cancer:
Also signs of liver toxicity: blood in urine, severe stomach pain/ nausea and vomiting
When should sulfonylureas be taken?
Patient with hepatic impairment prescribed a sulfonylurea?
Reduce the dose- sulfonylureas metabolised hepatically- they will accumulate and cause hypoglyceamia
How should Acarbose be taken?
Chewed with first mouthful of food/ with a bit of water immediately before food
What is the name of the thiazide diuretic that can be chronic intractable hypoglyceamia in Neonates/ children?
(remember diuretics can cause hyperglyceamia)
You have a patient suffering from newly diagnosed T2 diabetes with poor renal function, What would be your first line choice of antidiabetic?
A sulfonylurea- Gliclazide
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?
This is a NICE recommendation