Type 2 diabetes mellitus Flashcards
2
What are the medications used in type 2 diabetes?
• Metformin (usual first line treatment)
• Sulfonylurea (backup first line treatment and usual second line treatment)
○ Glimepiride
○ Gliclazide
○ Glipizide
• Thiazolidinedione (backup second line treatment and also a third line treatment)
○ Pioglitazone
• DPP-IV inhibitor (backup second line treatment and also a third line treatment)
○ Sitagliptin
• SGLT-2 inhibitor (backup second line treatment and also a third line treatment)
○ Empagliflozin
• GLP-1 agonists (third line treatment)
○ Lixisenatide
• Insulin (third line treatment)
What is the mechanism of action of metformin?
increases the action of insulin (Liver)
What is the mechanism of action of sulfonylurea?
- Increases insulin release (Pancreas)
○ Binds to sulfonylurea receptors on functioning pancreatic beta-cells
○ Binding closes the linked ATP sensitive potassium channels
○ Decreased potassium influx depolarises the beta-cell membrane
○ Voltage dependant calcium channels open and result in an influx in calcium cell surface
What is the mechanism of action of Thiazolidinedione?
- Increases the action of insulin (Liver)
○ Selectively stimulates the nuclear receptor peroxisome proliferator-activated receptor gamma (PPAR-gamma) and to a lesser extent PPAR-alpha
○ Modulates the transcription of the insulin sensitive genes involved in the control of glucose and lipid metabolism in the muscle, adipose tissue and the liver
○ Reduces insulin resistance in the liver and peripheral tissues
○ Increases the expense of insulin dependent glucose
○ Decreases withdrawal of glucose from the liver
○ Reduces quantity of glucose, insulin and glycated haemoglobin in the blood stream
What is the mechanism of action of DPP-IV inhibitors?
increases the release of insulin
What is the mechanisms of action of SGLT-2 inhibitors
Decreases blood glucose levels
What is the mechanisms of action of GLP-1 agonists?
Increases the release of insulin
What is the mechanisms of action of insulin?
increases blood insulin levels
What are the advantages of metformin?
- Increases cardiovascular outcomes and mortality in obese individuals with type 2 diabetes mellitus
- Cheap
- It is very effective (when used alone it can decrease the blood fasting glucose 22-26%)
- Normally well tolerated
- Not associated with weight gain
- HbA1c reduction by 12-17%
- Also used in pregnancy now
What are the disadvantages of metformin?
- Risk of lactic acidosis by inhibiting lactic acid uptake by the liver □ Hypoxia □ Renal failure □ Hepatic failure □ Alcohol abuse □ GI side effects 20-30% ® Dose dependant □ Risk of vitamin B12 malabsorption
What type of adverse drug reaction does sulfonylurea have?
- Displaces sulfonylurea from plasma proteins □ Clofibrate □ Phenylbutazone □ Salicylates □ Sulphonamides - Reduce hepatic sulfonylurea metabolism □ Dicumarol □ Chloramphenicol □ MAOIs □ Phenylbutazone - Decreased urinary excretion of sulfonylureas or their metabolites □ Allopurinol □ Probenecid □ Phenylbutazone □ Salicylates □ Sulphonamides - Intrinsic hypoglycaemic activity □ Insulin □ Alcohol □ β-blockers □ Salicylates □ MAOIs □ Guanethidine
What are the advantages of sulfonylurea?
- Used with metformin
- Rapid improvement in control
- Rapid improvement if symptomatic
- Rapid titration
- Cheap
- Generally well tolerated
What are the disadvantages of sulfonylureas?
- Risk of hypoglycaemia
- Weight gain
- Caution in renal and hepatic disease
- Cl in pregnancy and breastfeeding
- Side effects include:
□ Hypersensitivity and photosensitivity reactions
□ Blood disorders
What are the advantages of thiazolidinedione?
- Good for people if insulin resistance is significant
- HbA1c reduced by 0.6-1.3%
- Cheap
- Cardiovascular safety established
What are the disadvantages of Thiazolidinedione?
- Increased risk of bladder cancer
- Fluid retention
- Weight gain
- Fractures in females
□ Small increased risk
□ TZDs effect bone turnover
□ Reduced BMD
□ Initial report of increased distal fractures in women
