Endocrine Learning Objectives 9 Drug Class Mechanism of action Pharmacokinetics Adverse effects Contraindications Insulin lispro Insulin aspart

Short-Acting Insulins

Short acting insulin analogues Bolus dosing Match carbo content of meals

Onset in 5-15 min Duration 2-4 hr Commonly used in insulin pumps

Hypoglycemia Local injection reactions Weight gain

None

Insulin glulisine Onset in 5-15 min Duration 2-4 hr

Regular insulin Onset in 30 min Duration 2-4 hr Used IV in hospital

NPH insulin Insulin glargine Insulin detimir

Intermediate/Long-Acting Insulins

Intermediate/long acting insulin analogues Basal dosing Taken regularly independent of food intake

2x day dosing Onset in 2 hr Duration 18-28 hr Peak 6-10 hr 1x day dosing Onset in 2 hr Duration 20-24 hr 1 or 2x day dosing Onset in 2 hr Duration 6-24 hr

Glipizide Glyburide Glimepiride

Sulfonylureas

Bind to the sulfonylurea receptor (SUR1), closing the ATP-dependent potassium channel Kir6.2 Depolarizing the cell Increased insulin secretion. Expected decrease in A1c 1 to 2%

Dosed orally once or twice daily

Hypoglycemia Weight gain Use with caution in elderly, and in renal and liver failure

None

Nateglinide Repaglinide

Meglitinides

Similar MOA as sulfonylureas, but shorter acting. (bolus) Decrease in A1c 0.5 to 1.5%

Short acting. Dosed orally with each meal

Hypoglycemia (mild) Weight gain (mild) Use with caution in renal and liver failure

Metformin Biguanides

1st line drug in obese pts w DM2 Increases insulin sensitivity, esp liver. Decr hepatic glucose production Decrease in A1c 1 to 2%

Causes weight loss or is weight neutral Does not cause hypoglycemia

GI symptoms (metallic taste, nausea, diarrhea, cramping dose dependent) Lactic acidosis (rare) risk higher in renal, liver, heart disease, & severe illness

Renal insuff (cr > 1.4-1.5 mg/dL) Liver disease, alcohol abuse Heart failure Serious acute illness Age >80 years

Endocrine Learning Objectives 10

Rosiglitazone Pioglitazone

Thiazolidinediones TZD

Agonist @ PPAR g receptor Sensitizes skeletal muscle to insulin Increased glucose uptake incr GLUT-4 transporters Decr hepatic glucose production Decrease in A1c 0.5 to 1.4%

Delayed onset and offset of action May take 6-12 weeks to see peak effect Does not cause hypoglycemia Pioglitizone improves lipid profile

Weight gain Edema/fluid retention Risk of osteoporosis/fractures

Contra in HF, caution in LF Rosiglitizone may be associated with increased risk of CV events

Acarbose a-Glucosidase Inhibitors

Inhibits a-glucosidase, delaying digestion and absorption of carbs Decrease in A1c 0.5 to 0.8%

Flatulence/diarrhea Not well tolerated, not widely used

None

Exenatide Liraglutide

Incretin Mimetics

Promotes glucose-mediated insulin secr GLP-1 mimetics Decr hepatic glucose production Slows gastric emptying Decrease in A1c 0.5 to 1%

Reduces appetite and improves satiety. Does not cause hypoglycemia May support beta cell mass/survival

GI symptoms (nausea, vomiting) Use with caution in renal insufficiency

Sitaglipin Saxaglipin

DPP-4 Inhibitors

Inhibits DDP-4 which breaks down GLP-1 Incr GLP-1 levels and insulin secr Decrease in A1c 0.5 to 0.8%

None

Glucagon cAMP, gluconeo & glycogeno & increased blood glucose levels

None None