GENERAL: Incretin protein synthesized and released by L cells in ileum and colon in response to glucose ingestion. Secretion impaired in IGT and T2DM. 

MECH: Stimulates insulin secretion. Slows gastric emptying. Suppresses glucacon secretion. Promotes satiety. Improves insulin sensitivity (possibly). Enhances Beta-cell proliferation (maybe). 

KINETICS: Metabolized by dipeptydyl peptidase-4 (DDP-4). Half-life is 2-3 minutes.

GEN: Sulfonylurea drug. 

MECH: Stimulates insulin secretion from beta-cells in pancreas. Improved secretion in response to glucose. 

MECH: Bind SUR1 in beta-cell plasma membrane. Closes ATP sensitive K+ channels (which normally close in response to high intracellular glucose). Plasma membrane depolarizes. Voltage-sensitive Ca channels open. Ca flows into cell stimulating insulin release.

AE: Weight gain, hypoglycemia (esp if >60, bad renal fxn., bad nutr., liver dis., hypoalbuminemia, drug interactions).

CONTRAINDICATIONS: T1DM, pregnancy, lactation, allergy to sulfa drugs, diabetic ketoacidosis.

SYMPTOMS: Shaking, nervousness, sweating, extreme hunger, headache, mood/behavior change, confusion, palpitations, tingling hands tongue lips, vision change, slurred speach, poor coordination, dizzy, unresponsiveness, unconsciousness or seizures. 

MGMT: 1) Ingest carbs. 2) Use intravenous dextrose. 3) Use glucagon.

NOTE: Long-term diabetics may not notice these symptoms and just pass flat out.

GEN: Meglitinide class. Dose before meal. 

GEN: Biguanide class.

MECH: AMP Kinase activity increases with lowered cellular energy stores (low ATP)--metformin enhances AMPK activity. AMPK stimulates hepatic FA oxidation and decr. VLDL synth., incr. glucose uptake and nonoxidative metabolism. It also reduces gluconeogenesis (which is increased in T2DM) and lipogenesis. Increased muscle uptake of Glu too!

USE: Lowers blood glucose and insulin. Improves lipid profiles. Increases insulin sensitivity. Useful in obese patients. FIRST LINE IN DMTYPE2!!

AE: Does NOT cause weight gain. Does NOT cause hypoglycemia. GI - Anorexia, n + v, metallic taste, diarrhea. RARE - anemia, low B12, lactic acidosis.

CONTRAINDICATIONS: Renal or hepatic impairment, high alcohol intake, CHF, hypoxemia, infection, peri-operative periods, metabolic acidosis, pregnancy/lactation, >80.

GENERAL: Thiazolidinediones (TZD) class. EXPENSIVE! DO NOT CAUSE HYPOGLYCEMIA. Takes several weeks to act. Can cause resumption of ovulation.

MECH: Activates PPARgamma (normal ligand is FFA, eicosanoids) which is a transcription factor for a series of genes which increase insulin-dependent glucose disposal in skel muscle, decr. hepatic glucose production (decrease insulin resistance). Also lower blood glucose, insulin and TG levels and enhance adipose differentiation.

USE: Can be used in renal insufficiency!

CONTRA: Hepatic insuff., T1DM, kids, pregnants, lactators, CHF, macular edema.

AE: Fluid retention, weight gain, limb fracture, increase in CV events.

GENERAL: Thiazolidinediones (TZD) class. EXPENSIVE! DO NOT CAUSE HYPOGLYCEMIA. Takes several weeks to act. Can cause resumption of ovulation.

MECH: Activates PPARgamma (normal ligand is FFA, eicosanoids) which is a transcription factor for a series of genes which increase insulin-dependent glucose disposal in skel muscle, decr. hepatic glucose production (decrease insulin resistance). Also lower blood glucose, insulin and TG levels and enhance adipose differentiation.

USE: Can be used in renal insufficiency!

CONTRA: Hepatic insuff., T1DM, kids, pregnants, lactators, CHF, macular edema.

AE: Fluid retention, weight gain, limb fracture, decr. in MI, but incr. in bladder cancer.

GEN: Alpha glucosidase inhibitor. Weight neutral. No hypoglycemia caused.

MECH: Delay carb. absorption in gut by competitive inhibition of enzymes that break carbs into simples sugars like glucoamylase, sucrase and maltase. Only inh. lactose slightly (10%)--so no intolerance conferred.

USE: Only in patients who consume carbs. Moderate post-prandial glucose lowerer. Taken with meals.

AE: Diarrhea, fullness and abd. discomfort, farts, rare liver abn.

CONTRA: pregnants and lactators.

GEN: Alpha glucosidase inhibitor. Weight neutral. No hypoglycemia caused.

MECH: Delay carb. absorption in gut by competitive inhibition of enzymes that break carbs into simples sugars like glucoamylase, sucrase and maltase. Only inh. lactose slightly (10%)--so no intolerance conferred.

USE: Only in patients who consume carbs. Moderate post-prandial glucose lowerer. Taken with meals.

AE: Diarrhea, fullness and abd. discomfort, farts, rare liver abn.

CONTRA: pregnants and lactators.

GEN: GLP-1 Receptor Agonist (incretin). Injection only (twice daily). Promotes weight loss!

MECH: Stronger glucose-stimulated insulin secretion. Decr. glucagon secr. Slow gastric motility.

AE: GI stuff, acute pancreatitis, caution with renal insufficiency.

GEN: GLP-1 Receptor Agonist (incretin). Injection only (once daily). Promotes weight loss!

MECH: Stronger glucose-stimulated insulin secretion. Decr. glucagon secr. Slow gastric motility.

AE: GI stuff, acute pancreatitis, caution with renal insufficiency.

GEN: DPP-4 Inhibitors. Weight neutral.

MECH: Inhibit inhibitor of GLP-1. (Not as effective in increasing GLP-1 receptor as the GLP-1 agonists.

USE: T2DM alone or with metformin and/or sulfonylurea.

AE: Hypersensitivity, runny nose, URIs, headache.

GEN: Amylin analog.

MECH: Amylin is a peptide released with insulin post-prandially. Absent in Type 1s, variable in Type 2s. Slows gastric emptying, reduces post-prandial glucagon secretion, may reduce appetite.

USE: Inject before meal. Use with rapid-acting insulin.

AE: Risk of hypoglycemia. May promote weight loss. GI side effects.

GEN: RAPID insulin.

USE: Mealtime injections.

GEN: RAPID insulin.

USE: Mealtime injections.

GEN: RAPID insulin.

USE: Mealtime injections.

GEN: Duration is dose-dependent. LOW DOSE: INTERMEDIATE, HIGHER DOSE: LONG DURATION insulin.

LONG-ACTING. Cannot be mixed with other insulin in syringe--pH 4.

USE: Good baseline insulin--acts over 24 hrs.

1. Glucocorticoids - increase hepatic glu output and periph. insulin resistance.

2. Estrogens - increase periph insulin resistance.

3. Diuretics (thiazides) - deplete K+, decr. insulin secretion.

4. Diazoxide - blocks insulin secretion.

5. Sympathomimetic agents - block insulin secretion, stimulate hepatic glu output.

6. Nicotinic Acid - incr. insulin resistance, liver damage.