Pharmacological Treatment of Diabetes Flashcards
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Class of medications and examples
- Biguanides → Metformin (oral)
- Sulfonylureas → Tolbutamide, Glimepiride (oral)
- Thiazolidinediones → Pioglitazone, Rosiglitazone (oral)
- a-glucosidae inhibitors → Acarbose (oral)
- Meglitinides → Repaglinide, Nateglinide (oral)
- SGLT2 inhibitors → Canagliflozin, Dapagliflozin (oral)
- Insulin → Many, from rapid to long-acting (Inj.)
- GLP-1 analogs → Exenatide, Liraglutide (Inj.)
- DPP4 inhibitors → Sitagliptin, Saxagliptin (oral)
- TZIELD → teplizumab-mzwv (inj.)
biguanide mechanism
decreases hepatic glucose production, decreases intestinal absorption of glucose, and improves insulin sensitivity by increasing peripheral glucose uptake and utilization
* metformin
* first line medication
biguanide advantages
decreases risk for diabetes related end-points
* reduce plasma TAG and LDL levels
* Dont see weight increases
* Can be used as mono therapy
* Lower costs
* Improves insulin sensitivity
biguanide disadvantages
risk is minimal
* GI disturbances
* lactic acidosis
* Cannot be used if impaired renal function and liver toxicity
* Biggest concern is hypoglycaemia
sulfonylureas mechanism of action
Primary is increase insulin secretion where it binds on beta cells receptors and similar mechanism to glucose (K+ATP channel closes, Ca opens etc.)
* bypass glucose metabolism and force insulin secretion
* tolbutamide
* glimepiride
sulfonylureas advantages
- low cost med
- No effect on plasma lipid levels
- no injections, oral med, start with small dose and titrate up
- Have huge and rapid effect, induces insulin excretion in a matter of seconds and reduces the plasma glucose
sulfonylureas disadvantages
- weight gain
- Can build a tolerance (around 10 years)
- At risk of hypoglycaemia
- Only beneficial for those with mild to moderate hyperglycaemia (??)
- Need functional beta cells
TZDs mechanismof action
Binds to PPARs as agonist ligand regulating insulin response primarly in fat metabolism but also glucose uptake in muscle and liver
* pioglitazone
* rosiglitazone
TZDs advantages
- Dont cause as much hypoglycaemia
- no contraindication with renal disease
- Increase in HDL
- Decreases plasma TAG
TZDs disadvantages
- Costly
- Weight gain
- increased LDL –> hypercholesterolemia
- Fluid retention —> Edema
- ALT increase —> hepatic toxicity
- Teratogen
a-glucosidae inhibitors mechanism of action
inhibit a-glucosidase enzymes in lumen of intestine that break down complex CHO so digestion of CHO is delayed and slows down entry of glucose to blood stream (↓ absorption) allowing more time for insulin to be released which helps manage post prandial
* acarbose
a-glucosidae inhibitors advantages
- less hypoglycaemic effect since it just delays/ prevents absorption of glucose
- No resistance over time
- No change in weight
- No change in LDL and HDL
- Original mode of action so can be used with another mode of action
a-glucosidae inhibitors disadvantages
- not as effective as monotherapy
- Effectiveness may be reduced if diet is already reduced in CHO
- GI disturbance because CHO reaches parts of colon not normally found in
Meglitinides mechanism of action
similar to sulfonylureas → Primary is increase in insulin secretion where it binds on beta cells receptors and similar mechanism to glucose (K+ATP channel closes, Ca opens etc. ). So bypass glucose metabolism and force insulin secertion
* Repaglinide
* Nateglinide
Meglitinides advantages
- low cost med
- No effect on plasma lipid levels
- no injections, oral med, start with small dose and titrate up
- Have huge and rapid effect, induces insulin excretion in a matter of seconds and reduces the plasma glucose
Insulin mechanism of action
Different forms of insulin: rapid, longer acting, split dose regime, combination
* individualistic → person chooses what works best for them
* Got good at estimating how much they need
What kind of hormone is GLP-1?
Glucagon-like peptide-1 (GLP-1) → an incretin hormone
* has similar gene to proglucagon but is cleaved differently in the intestine
What is the incretin effect?
If sweetened beverage is orally taken glucose goes up and insulin goes up as in the blue line. But If you inject same amount of glucose less insulin is released as in the purple line. Therefore something along the GI tract helps with insulin secretion and need these for full insulin secretion effect (GLP-1)
What happens to GLP-1 in T2D?
reduced in IGT and even more reduced in T2D
* Diabetic patients show normal response if injected with GLP-1
What does GLP-1 improve?
- Increases insulin biosynthesis and secretion
- Promotes beta-cell mass expansion via cell proliferation and survival
- Other effects include: slowing of GI transit, Induces satiety (increases appetite signal in the brain), neuro/ cardio protection
