Management Of Type 2 Diabetes Flashcards
Why is Metformin usually first choice?
Improves outcome
Well tolerated
Cheap
Wheat are the defects in T2DM?
Beta cell dysfunction
Diminished incretin effect
Excess glucagon
Insulin resistance
Where does Metformin mainly work?
The liver and muscles
What type of drug is Metformin?
Biguanide
What does Metformin do?
Improve insulin sensitivity
How does Metformin improve insulin sensitivity?
Affects glucose production, decrease fatty acid synthesis
Improve receptor function
Inhibit gluconeogenic pathways
What is Metformin half life?
6 hours
What are the advantages of Metformin?
Improves CV outcomes and mortality in obese T2DM
Efficacious
Well tolerated
Not associated with weight gain
HbA1c 12-17% reduction
Used in pregnancy
Cheap
What are disadvantages of Metformin?
GI side effect
Risk of lactic acidosis by inhibiting lactic acid uptake by liver
-hypoxia
-renal failure
-hepatic failure
-alcohol abuse
Risk vit B12 malabsorption
What are sulphonylureas?
The gli…ides - glimepiride, gliclazide, glipizide
When to use sulphonylureas?
If osmotic symptoms or HbA1c increase rapidly titration based on home blood glucose monitoring
What does sulphonylureas do?
Increase insulin release
Where does sulphonylureas act?
On the pancreas
What is the mechanism of action of sulphonylureas?
Bind to sulfonylurea receptors (SUR-1) on functioning pancreatic beta cells
Binding closes the linked ATP- sensitive potassium channel
Decreased potassium influx depolarisation of the beta cell membrane
Voltage- dependent calcium channels open and result in an influx of calcium
Translocation and exocytosis of secretory granule of insulin to the cell surface
What are the advantages of sulfonylurea?
Rapid improvement of control
Rapid improvement if symptoms
Rapid titration
Cheap
Generally well tolerated
What a re the disadvantages of sulfonylurea/
Hypoglycaemia risk
Weight gain
Caution in renal and hepatic disease
CI in pregnancy and breast feeding
SE
-hypersensitivity and photosensitive reactions
-blood disorders
What are thiazolidinediones?
The …glitazones
What do thiazolidinedones do?
Improve insulin action
What do glitazones act on?
Muscle, liver and adipose tissue
What is a thiazolidinediones?
Pioglitazone
What is the mechanism of pioglitazone?
Selectively stimulates the nuclear receptor peroxisomes proliferator- activated receptor gamma and the a lesser extent PPAR-alpha
Modulates the transcription of insulin sensitive genes involved in the control of glucose and lipid metabolism in the muscle, adipose tissue and the liver
What does pioglitazone cause?
Reduce insulin resistance in the liver and peripheral tissues
Increase the expense of insulin dependent glucose
Decrease the withdrawal of glucose from liver
Reduce quantity of glucose, insulin and glycogen Haemoglobin in the bloodstream
What are the advantages of pioglitazone?
Good for signicant insulin resistance
HbA1c by o.6-1.3%
Cheap
CV safety established
What are the disadvantages of pioglitazone/
Increase risk of bladder cancer
fluid retention
Weight gain
Fractures in females
Is insulin treatment the last resort?
No
What does insulin have a low risk of/
Hypoglycaemia
What is the treatment regimen of insulin in t2dm?
Once daily injection
Usually at bedtime
What are different types of gliflozins?
Canaglifolozin, dapagliflozin and empagliflozin
What do gliflozins do?
Selectively inhibit SGLT2 in the renal proximal tubule
What are the effects of SLGT2 inhibitors?
Gets rid of glucose/ more glycosuria
- lowers HbA1c
Gets rid of water/ osmotic diuresis
- hypotension and dehydration
Gets rid of calories/ wastes glucose
- lose weight with same intake
Gets rid of sodium/less reuptake
- lowers systolic bp
Greater risk of urogenital infection
- cystitis and candidiasis
What is the primary CV outcome of SGLT2 inhibitors?
Composite of CV death, nonfatal MI, or non fatal stroke
What is the CV outcome of SGLT2 inhibitors?
Composite of primary + hospitalisation of unstable angina
What are the renal outcomes of canagliflozin?
Composite of end stage kidney disease, doubling of serum creatinine level, death from renal or CV causes
What is the dose of canagliflozin?
What renal impairment does canagliflozin cause?
What is the dose of empagliflozin?
What is the renal impairment of empagliflozin?
What is the does of dapagliflozin?
What renal impairment does dapagliflozin cause?
When are SGLT2-I used
2nd line therapy in thsoe at high CVrisk
1st line in those of high cv risk when Metformin not tolerated
What is the advantage of SGLT2 - I
Weight loss
No risk of hypoglycaemia
Good effect on glycaemic control
Beneficial on cv mortality and renal outcomes
2nd or 3rd line agent
Can add to insulin regimes in T2DM
What are the disadvantages of SGLT2 inhibitors?
Expensive
SE
-UTI, fungal infection, osmotic symptoms
Risk of digital amputation
Risk of DKA
CI in pregnancy and BF
Cannot use in renal impairment
How do gliflozins interfere in renal glucose handling?
Block the Na glucose transporter 2 in the proximal tubule => increase urinary glucose excretion
What type of drugs are GLP1 and DPP IV?
Incretin mimetics
What are incretins?
GLIPTINS
TIDES
What are example of DPPIV- inhibitors
Saxagliptin, sitagliptin, vildagliptin
What do gliptins do?
Increase insulin release
What do gliptins act on?
Pancreas
What is the mode of action of DPPIV-I?
Increase insulin from beta cells -> insulin increases peripheral glucose uptake -> decrease glucose
Decrease glucagon from alpha cells -> increase insulin and decreased glucagon reduce hepatic glucose output -> decrease glucose
What are the advantages of DPPIV-I?
Well tolerated
Used 2nd or 3rd line
Can be used in renal impairment
No risk of hypoglycaemia
Weight neutral
What are disadvantages of DPPIV- inhibitors?
Trial data shows relatively effects of glycaemic control
CI in pregnancy and BF
SE
- nausea
What are examples of GLP-1 analogues?
Exenatide, liraglutide, lixisenatide
What do GLP-I cause/
Increase insulin release
What is the mode of action of GLP1 analogues?
Increase insulin from beta cells -> insulin increases peripheral glucose uptake -> decrease glucose
Decrease glucagon from alpha cells -> increase insulin and decreased glucagon reduce hepatic glucose output -> decrease glucose
What are the advantages of GLP-1 analogue?
Weight loss
No risk of hypoglycaemia
3rd line agent
Can be used with basal insulin
Some have benefited for CV disease
What are disadvantages of GLP-1 analogues?
Injection
Expensive
CI in preg and BF
Se
-nausea, vomiting
