Treatment of Type 2 Diabetes: Oral Agents Flashcards
Organ systems targeted by glucose-lowering therapies + role in regulating glucose homeostasis
- Pancreas
- Secretes insulin and glucagon
- Liver
- Major player in gluconeogenesis, glycogen synthesis, etc
- Muscle
- Stores glycogen, undergoes glycogenolysis, takes up glucose when insulin is high
- Adipose tissue
- Takes up glucose when insulin is high
- GI
- Secretes incretin enhancers which assist insulin-mediated reduction of glucose levels
Main classes of non-insulin medications
- Sulfonylureas
- ex. glipizide, glyburide
- Biguanide
- ex. Metformin
- Thiazolidinediones
- ex. Pioglitazone, rosiglitazone
- Incretin enhancers (GIP, GLP, DDP)
- GLP-1 Agonists
- ex. exenatide, liraglutide
- DPP4 inhibitors
- ex. sitagliptin
- Amylin analogue
- ex. pramlintide
Sulfonylureas: examples
ex. glipizide, glyburide
Sulfonylureas: MOA
- MOA: Increase endogenous insulin secretion by closing ATP sensitive K+ channels → depolarization → Voltage gated Ca2+ channels → exocytosis of insulin
- SOA: Pancreas
Biguanide: examples, MOA
- ex. Metformin
- MOA: Acts at the liver to potentiate suppressive effects of insulin on hepatic glucose production
- SOA: Liver
Thiazolidinediones: examples
ex. Pioglitazone, rosiglitazone
Thiazolidinediones: MOA
- Insulin sensitizing → activates PPAR ɣ receptor ==> increases insulin action ==> transcription of genes involved in adipocyte differentiation, glucose & lipid metabolism amongst other.
- SOA:
- Mainly skeletal muscle & adipose tissue
- (liver - decreases gluconeogensis)
Incretin enhancers (GIP,GLP, DDP): MOA
- MOA: Incretins contribute to the control of postprandial glycemia by ↑ insulin
- SOA:
- GI
- pancreas
GLP-1 Agonists: exmaples
ex. exenatide, liraglutide
GLP-1 Agonists: MOA
- MOA: GLP-1 amplifies glucose stimulated insulin secretion, inhibits glucagon secretion, slows gastric emptying, and increases satiety in the CNS
- SOA:
- GI
- pancreas
DPP4 inhibitors: examples
sitagliptin
DPP4 inhibitors: MOA
- MOA: DPP4 inhibition prevents GLP-1 degradation ==> Enhance pancreatic insulin secretion and suppress glucagon, no effect on appetite or gastric emptying
- SOA:
- GI
- pancreas
Amylin analogue: examples
pramlintide
Amylin analogue: MOA
- MOA: Amylin is a peptide co-secreted with insulin, and inhibits gastric emptying and glucagon secretion acutely, leading to reduced food intake and weight loss
- SOA:
- GI
- pancreas
Blood glucose and HbA1c goals for adults w/DM
- Hemoglobin A1c (HbA1c or A1c)
- < 7% (general), 6% (individual)*
- without significant hypoglycemia
- Fasting glucose
- 70-130 mg/dL
- 2 hour postprandial glucose
- < 180 mg/dL
Routine monitoring for adults with diabetes
- home blood glucose monitoring
- check fingerstick blood glucoses at least twice per day at specific timepoints:
- fasting, before lunch, before dinner, and at bedtime
- record: glucose results, insulin admin, diet, physical activity
Characteristics of incretin enhancers
- Incretin enhancers are GI mediated molecules that assist insulin-mediated glucose reduction post-prandium
- serum insulin levels increase significantly more upon oral dosage of glucose vs. IV due to incretin enhancers
- main incretin enhancers: GLP-1 & GIP
- GLP-1 = glucagon-like peptide-1
- GIP = glucose-dependent insulinotropic polypeptide
GLP-1 and T2D
Type 2 diabetics have normal or elevated levels of GLP-1 but are resistant to its insulin stimulatory actions
Fxn of DPP-4 (dipeptidyl peptidase-IV)
an enzyme that rapidly inactivates (within minutes) GLP-1 & GIP
