DM5

What is the mechanism of action (MOA) of Thiazolidinediones (Pioglitazone)?

Activate the nuclear transcription factor PPAR-g

What is the primary action and clinical advantages of Pioglitazone?

• Action: ↑ peripheral insulin sensitivity\n- Advantages: no hypoglycemia

What are the highlighted disadvantages and cost of Pioglitazone “TZD”?

• Disadvantages: weight gain, edema, HF, fractures

• Cost: high

What is the mechanism and primary action of Sulfonylureas (Glyburide, Glipizide, Gliclazide)?

closes K ATP channels on β-cell.

↑ insulin secretion

What are the advantages of Sulfonylureas?

Generally well tolerated

What are the highlighted disadvantages and cost of Sulfonylureas?

• Disadvantages: serious hypoglycemia, weight gain, may blunt MI preconditioning, low "durability"

• Cost: low

What is the mechanism and primary action of Meglitinides (Repaglinide, Nateglinide)?

closes K ATP channels on ẞ-cell.

↑ insulin secretion

What is the unique advantage of Meglitinides compared to other secretagogues?

Accentuated effect around meal ingestion

What are the disadvantages and cost of Meglitinides?

• Disadvantages: hypoglycemia, weight gain

• Cost: medium

What is the mechanism of action (MOA) of SGLT2 inhibitors (Canagliflozin and dapagliflozin)?

Inhibit SGL2 glucose reabsorption in the kidney.

What are the physiological actions and a key advantage of SGLT2 inhibitors?

• Actions: ↓ reabsorption of glucose ↑ urinary glucose excretion, ↓ reabsorption of Na

• may reduce systolic blood pressure.

What are the highlighted disadvantages and cost category for SGLT2 inhibitors?

• Disadvantages: candidiasis, UTI, and urinary frequency, hypotension particularly in the elderly.

• Cost: medium