Treatment of Type 2 Diabetes: Oral Agents

Question 1

Organ systems targeted by glucose-lowering therapies + role in regulating glucose homeostasis

Answer 1

• 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

Question 2

Main classes of non-insulin medications

Answer 2

• 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

Question 3

Sulfonylureas: examples

Answer 3

ex. glipizide, glyburide

Question 4

Sulfonylureas: MOA

Answer 4

• MOA: Increase endogenous insulin secretion by closing ATP sensitive K+ channels → depolarization → Voltage gated Ca2+ channels → exocytosis of insulin
• SOA: Pancreas

Question 5

Biguanide: examples, MOA

Answer 5

• ex. Metformin
• MOA: Acts at the liver to potentiate suppressive effects of insulin on hepatic glucose production
• SOA: Liver

Question 6

Thiazolidinediones: examples

Answer 6

ex. Pioglitazone, rosiglitazone

Question 7

Thiazolidinediones: MOA

Answer 7

• 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)

Question 8

Incretin enhancers (GIP,GLP, DDP): MOA

Answer 8

• MOA: Incretins contribute to the control of postprandial glycemia by ↑ insulin
• SOA:
  
  • GI
  • pancreas

Question 9

GLP-1 Agonists: exmaples

Answer 9

ex. exenatide, liraglutide

Question 10

GLP-1 Agonists: MOA

Answer 10

• MOA: GLP-1 amplifies glucose stimulated insulin secretion, inhibits glucagon secretion, slows gastric emptying, and increases satiety in the CNS
• SOA:
  
  • GI
  • pancreas

Question 11

DPP4 inhibitors: examples

Answer 11

sitagliptin

Question 12

DPP4 inhibitors: MOA

Answer 12

• MOA: DPP4 inhibition prevents GLP-1 degradation ==> Enhance pancreatic insulin secretion and suppress glucagon, no effect on appetite or gastric emptying
• SOA:
  
  • GI
  • pancreas

Question 13

Amylin analogue: examples

Answer 13

pramlintide

Question 14

Amylin analogue: MOA

Answer 14

• 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

Question 15

Blood glucose and HbA1c goals for adults w/DM

Answer 15

• 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

Question 16

Routine monitoring for adults with diabetes

Answer 16

• 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

Question 17

Characteristics of incretin enhancers

Answer 17

• 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

Question 18

GLP-1 and T2D

Answer 18

Type 2 diabetics have normal or elevated levels of GLP-1 but are resistant to its insulin stimulatory actions

Question 19

Fxn of DPP-4 (dipeptidyl peptidase-IV)

Answer 19

an enzyme that rapidly inactivates (within minutes) GLP-1 & GIP