Management of Type II Diabetes Flashcards by Sophie Pitcairn

Why is metformin normally first choice?

Improves outcomes, well tolerated and cheap

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What solution does metformin do?

Improves insulin action

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Where does metformin work?

On the liver and muscles

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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

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What is the half life of metformin?

6 hrs

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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

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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

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What are some types of Sulphonylureas?

Glimepiride, Gliclazide and Glipizide
The Gli…ides

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When are Sulphonylureas used?

If osmotic symptoms or HbA1c increasing rapidly titration based on home glucose monitoring

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What is the solution of Sulphonylureas?

Increases insulin release - works on defected Beta cell function but lowers across all body

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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

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Describe glimepiride

1-6mg given daily
Metabolised by liver
60% renal excretion in 24 hrs
Actions lasts 12-24hrs

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Describe gliclazide

40-320mg twice daily
Metabolised by liver
Less than 5% excretion in 24hrs
Action lasts 10-15hrs

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Describe Glipizide

2.520mg twice daily
Metabolised by liver
90% excretion in 3 days
Action lasts 6-12 hrs

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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

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What are the advantages of Sulphonylureas?

Rapid improvement in control
Rapid improvement if symptomatic
Rapid titration
Cheap
Generally well tolerated

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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

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What thiazolidinedione (glitazone) is used?

Pioglitazone

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What is the solution of Pioglitazone?

Improves insulin action by acting on liver, adipose tissue and muscle

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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

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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