Management of Type II Diabetes Flashcards
Why is metformin normally first choice?
Improves outcomes, well tolerated and cheap
What solution does metformin do?
Improves insulin action
Where does metformin work?
On the liver and muscles
What is the mechanism of action of metformin?
Biguanide
Improves insulin sensitivity - affects glucose production and decreases FA synthesis
Improves receptor function and inhibits gluconeogenic pathways
What is the half life of metformin?
6 hrs
What are the advantages of metformin?
Improves cardiovascular outcomes and mortality in obese
Efficacious
Normally well tolerated
Not associated with weight gain
HbA1c reduction
Also can be used in pregnancy
Cheap
What are the disadvantages of metformin?
GI side effects - diarrhoea and bloating
Risk of lactic acidosis by inhibiting lactic acid uptake by liver
Risk vitamin B12 malabsorption
What are some types of Sulphonylureas?
Glimepiride, Gliclazide and Glipizide
The Gli…ides
When are Sulphonylureas used?
If osmotic symptoms or HbA1c increasing rapidly titration based on home glucose monitoring
What is the solution of Sulphonylureas?
Increases insulin release - works on defected Beta cell function but lowers across all body
What is the mechanism of action of Sulphonylureas?
Binds to sulfonylurea receptor on functioning pancreatic beta cells
Binding closes the linked ATP sensitive potassium channels
Decreased influx - depolarisation of beta cell
Voltage gated Ca channels open - translocation and exocytosis of secretory granules of insulin
Describe glimepiride
1-6mg given daily
Metabolised by liver
60% renal excretion in 24 hrs
Actions lasts 12-24hrs
Describe gliclazide
40-320mg twice daily
Metabolised by liver
Less than 5% excretion in 24hrs
Action lasts 10-15hrs
Describe Glipizide
2.520mg twice daily
Metabolised by liver
90% excretion in 3 days
Action lasts 6-12 hrs
What are some drug interactions with Sulphonylureas?
Displace sulfonylureas from plasma proteins
Reduce hepatic sulfonylurea metabolism
Decrease urinary excretion of sulfonylureas or their metabolism
Intrinsic hypoglycaemic activity
What are the advantages of Sulphonylureas?
Rapid improvement in control
Rapid improvement if symptomatic
Rapid titration
Cheap
Generally well tolerated
What are the disadvantages of sulphonylureas?
Risk of hypoglycaemia
Weight gain
Caution in renal and hepatic disease
CI in pregnancy and breast feeding
Side effects - hypersensitivity and photosensitivity reaction, and blood disorders
What thiazolidinedione (glitazone) is used?
Pioglitazone
What is the solution of Pioglitazone?
Improves insulin action by acting on liver, adipose tissue and muscle
What is the mechanism of action of pioglitazone?
Selectively stimulates the nuclear receptor peroxisome proliferator activated receptor gamma and to lesser extent PPAR alpha
Modulates transcription of insulin sensitive genes
What is the action of Pioglitazone?
Reduces insulin resistance in liver and peripheral tissues, increases expense of insulin dependant glucose, decreases withdrawal of glucose from liver, and reduces quantity of glucose, insulin and glycated haemoglobin
What are the advantages of Pioglitazone?
Good if people are insulin resistance is significant
HbA1c reduced by 0.6-1.3%
Cheap
Cardiovascular safety
What are the disadvantages of Pioglitazone?
Increase risk of bladder cancer
Fluid retention - CCF
Weight gain
Fractures in females
When is insulin used in T2D?
Progressive relative insulin deficiency
Use may become inevitable
Describe supplementary insulin therapy
Easy introduction to insulin
Low risk of hypoglycaemia
Possible weight gain
When is isophane insulin given?
Humulin I or H insulatard
Once daily injection
Usually at bedtime
What are some gliflozins (SGLT2 inhibitors)?
Canagliflozin, Dapagliflozin and Empagliflozin
What is the solution of gliflozins?
Increase excretion of glucose in urine as majority of glucose is reabsorbed by SGLT2 in proximal tubule - selectively inhibit receptors
What are the SGLT2 inhibitor effects?
Gets rid of glucose - lowers HbA1c
Gets rid of water - hypotension and dehydration
Gets rid of calories - lose weight with same intake
Gets rid of sodium - lowers systolic blood pressure
Greater risk of urogenital infection
Describe SGLT2 inhibitors and CV safety
Reduces CV outcomes and mortality
Describe renal outcomes with canagliflozin
Reduction in renal outcomes like end stage kidney disease and mortality
Describe dapagliflozin and heart failure
Reduces HF and its outcomes/ mortality
Describe Canagliflozin
100mg once daily
Do not start if eGFR under 30
On GJF
Describe Empagliflozin
10mg once daily
Without CV disease then don’t start if eGFR is under 60 and if under 40 with CV disease then stop
On GJF
Describe dapagliflozin
10mg once daily
Do not start if eGFR is under 15
On GJF
When is SGLT2 inhibitors used?
2nd line is those with high CV risks
1st line in those whose CV risk is high but metformin not tolerated
Check if increased risk of DKA
What are the advantages of SGLT2 inhibitors?
Weight loss
No risk of hypoglycaemia
Good effects on glycaemic control
Beneficial effect for CV and renal outcomes
2nd or 3rd line agent
Can add to insulin regimens
What are the disadvantages of SGLT2 inhibitors?
Expensive
Side effects - UTI, fungal infections and osmotic agents
Risk of digital amputation
Risk of DKA
Cl in pregnancy and breast feeding
Don’t use in renal impairment
What are incretin mimetics?
GLP1 - gliptins
DPPIV - tides
There is diminished incretin effect if have T2D
What are types of DPPIV inhibitors?
Gliptins
Saxagliptin, sitagliptin and vildagliptin
What is the solution of incretin mimetics?
Increase insulin release
What is the mode of action of gliptins?
DPP4 inhibitors that delay the breakdown of incretins and thereby increase active incretin levels
Increase of incretins - increase insulin and decreases glucagon so decreases glucose
What are the advantages of DPPIV inhibitors?
Usually well tolerated
Can be used as 2nd or 3rd line agents
Can be used in renal impairment
No risk of hypoglycaemia
Weight neutral
What are the disadvantages of DPPIV inhibitors?
Relatively small effects on glycaemic control
CI in pregnancy and breastfeeding
Nausea
What are some GLP-1 analogues?
Tides
Exenatide, Liraglutide and Lixisenatide
What is the mode of action for GLP1 analogues?
Injectable analogues of GLP1 - resistant to enzyme degradation and greatly prolonged biological half life
Release incretin gut hormones so increase insulin and decrease glucagon
What are the guidelines for GLP1 analogues?
BMI<35
Stop after 6/12 unless HbA1c -1% and weight -3%
3rd line agent
Can be in combination with oral agents and/ or basal insulin
What are the advantages of GLP-1 analogues?
Weight loss
No risk of hypoglycaemia
3rd line agent
Can be used with basal insulin
Some have benefit for CV disease
What are the disadvantages of GLP-1 analogues?
Injection
Expensive
Cl in pregnancy and breastfeeding
Nausea and vomiting
What medication is given first line not at high CV risk?
Metformin
What medication is given if chronic heart failure or established atherosclerotic CVD?
Metformin
As soon as metformin is tolerable then SGLT2 inhibitor and if metformin contraindicated then SGLT2 inhibitor alone
Same for high risk CVD
What is considered if metformin is contraindicated?
DPP4 inhibitors - gliptins
Pioglitazone
Sulfonylurea
SGLT2 inhibitor for some people