Pharm Management of T2D Flashcards
Basal vs prandial glucose
Basal: suppresses glucose production between meals and overnight
Prandial: facilitates glucose uptake after meals
When insulin is subcutaneously injected, it forms…
Hexamers (these minimally diffuse, need to break up into monomer form)
4 current basal insulins
Insulin glargine
Insulin glargine U300
Insulin detemir
Insulin degludec
3 types of current bolus insulins
Human regular insulin (humulin R, novolin Toronto)
Analogue rapid insulins (aspart, lispro, glulisine)
Analogue ultra-rapid insulins (ultra-rapid aspart)
General mechanism of action for
- Metformin
- Sulfonylureas
- Thiazolidinediones
- Incretins
- SGLT2 inhibitors
- Alpha-glucosidase inhibitors
- Decreases hepatic glucose output, decreases insulin resistance
- Increases insulin secretion
- Decreases insulin resistance
- Increases insulin secretion, decreases glucose output, decreases gastric emptying
- Increases urinary glucose excretion
- Decreases carb breakdown/absorption
Metformin mechanism
Overall: Decreases hepatic glucose output, decreases insulin resistance
Decrease hepatic glucose production through mild inhibition of the mitochondrial respiratory-chain complex 1
Decrease intestinal glucose absorption
Anti-oxidant properties of metformin on endothelial cells
Metformin
4 advantages
2 disadvantages
Pros: effective glucose lowering, no significant hypoglycemia, durable effect, not associated with weight gain or CV side effects
Cons: GI side effects, rare lactic acidosis
Examples of sulfonylureas
-ide drugs Glyburide Gliclazide Glimepiride Repaglinide Nateglinide
Sulfonylurea mechanism
Act at the beta cell
Block the K ATPase channel, inhibit K efflux, cell depolarizes, opens voltage-dependent Ca channel, Ca influx, release of insulin from vesicles
Sulfonylurea advantages and disadvantages
Pros: cheap, easy to give, effective at lowering glucose
Cons: prone to weight gain, risk of hypoglycemia
Incretins
GI hormones (GIP and GLP1) that are stimulated by food and inactivated by DPP-4 They augment physiologic insulin secretion
How do GLP-1 receptor agonists and DPP-4 inhibitors work?
They prevent the breakdown of incretins (DPP4 inhibitors) or directly stimulate the GLP1 receptor (GLP1 RAs) to stimulate the beta cell to secrete insulin
4 GLP-1 actions
Decreased appetite
Slows gastric emptying
Decreased hepatic glucose output
Increased insulin secretion (glucose dependent)
SGLT2 inhibitors advantages and disadvantages
Pros: easy to administer, effective glucose lowering, promotes weight loss, lowers BP, low risk of hypoglycemia, CV benefits in high risk patients
Cons: polyuria, frequency, volume depletion, hyperkalemia, yeast infections, rare cases of euglycemia DKA
Thiazolidinediones mechanism
PPAR-y activators (on adipose)
Reduces insulin resistance, modifies adipocyte differentiation, inhibits VEGF-induced angiogenesis, reduces leptin levels
TZDs pros and cons
Pros: easy to admin, effective glucose lowering, durable
Cons: cost/coverage, side effects (weight gain from fat storage, edema, worsens CHF, bone fractures in osteoporosis)
Only use these in younger men now
a-glucosidase inhibitor mechanism
Ex: acarbose
Binds to glucosidase enzyme in gut
Competitively inhibits the breakdown of non-absorbable complex polysaccharides
Reduces monosaccharide absorption (glucose)
What is the preferred first line therapy? Why?
Metformin
It is associated with lower all-cause mortality and CV disease mortality than sulfonylureas
In T2D, when would you start on insulin as an initial choice of therapy?
When there is symptomatic hyperglycemia and/or metabolic decompensation (polyuria, polydipsia, weight loss, volume depletion)
- 3 drugs with low risk for hypoglycemia
1. 2 drugs with high risk for hypoglycemia
- metformin, incretin agents, SGLT2 inhibitors
2. insulin, sulfonylureas
- 2 drugs that cause weight loss
2. 3 drugs that cause weight gain
- GLP-1 analogs, SGLT2 inhibitors
2. insulin, TZDs, sulfonylurea
2 drugs that are CV protective
SGLT2 inhibitors
GLP-1 agonists
