Oral Anti-diabetic agents Flashcards
MOA: enhances secretion of insulin by beta cells, decreases glucagon production, and increases tissue sensitivity to insulinGlimepiride (sulfonylurea)
Glimepiride (sulfonylurea)
How does glimepiride increase the secretion of insulin from beta cells?
By blocking the same ATP-sensitive K+ channels that are blocked by ATP when endogenous glucose is high
Administered once-daily with ER formulation or 30 minutes before meals
Metabolized by liver AND kidneys
Contraindication in patients with liver or kidney disease
Glimepiride (sulfonyurea)
AEs: hypoglycemia, esp. when given with insulin (not as bad as earlier formulations)
Weight gain
GI/skin/liver/blood abnormalities
Glimepiride (sulfonylurea)
Similar mechanism as for SUs, but lower effect
Faster, but shorter action than SUs
Perhaps safer in kidney disease
Meglitinides
MOA: targets AMP kinase, a critical regulator of glucose metabolism
Metformin (biguanide, additional liver enzyme targets are being identified or implicated)
MOA: effects primarily in the LIVER, decreases glucose production, increases glucose uptake, so makes insulin work better
Metformin (biguanide)
T/F: Metformin cannot be used with sulfonylureas, due to the risk of hypoglycemia
False. Different MOAs and metformin does not cause hypoglycemia
Administered once-daily with ER formulation or 2-4 times per day after meals
Renal excretion without metabolism (concerns with moderate-severe kidney disease)
Metformin (biguanide)
AEs: does not cause hypoglycemia or weight gain Lactic acidosis GI effects (metallic taste, diarrhea, nausea, vomiting, anorexia)
Metformin (biguanide)
This potentially serious side effect from this drug is more common in patients with impaired renal function, excessive alcohol intake, and/or increased hypoxemic conditions.
What is lactic acidosis from metformin (biguanide)?
Microbial sugars that inhibit sugar metabolizing enzymes, like a-glucosidase and amylase, in the gut
Acarbose
MOA: slow formation and absorption of glucose in the gut, by inhibiting hydrolysis of disaccharides and complex carbohydrates
Acarbose
Poorly absorbed, remains in the gut
Not a powerful drug. Mainly used in mild disease or with other agents.
Acarbose (decrease glucose formation in the gut)
Do not cause hypoglycemia ON THEIR OWN, but with insulin or other oral agents, can increase hypoglycemia risk
Acarbose
What do you give someone on acarbose who is hypoglycemic?
Glucose (NOT SUCROSE, or other di+saccharides)
AEs: flatulence, cramps, diarrhea that diminish with time and are additive with another agent with similar side effects
Limited use in the US because of all the farting
Acarbose (additive with metformin)
MOA: binds and activates peroxisome proliferator-activated receptor-y (PPAR-y), a nuclear transcription factor receptor that enhances transcription of insulin-responsive genes
Pioglitazone, rosiglitazone (thiazolidinediones, TZDs)
Effects: decreases gluconeogenesis, glucose output, and triglyceride synthesis is LIVER
Increases glucose uptake and utilization in MUSCLE
Increases glucose uptake and decreases fatty acid production in ADIPOCYTES
Pioglitazone, rosiglitazone (TZDs)
Used for Type 2 insulin resistance
Best taken with food one time daily
Metabolized in liver (safe with renal disease)
Pioglitazone, rosiglitazone
AEs: hepatotoxicity and fatal liver disease
CVD/death risk
May increase bladder cancer risk
Increase fracture risk
Pioglitazone, rosiglitazone
AEs: dose-dependent edema, increase in CHF, myocardial ischemia, angina, and myocardial infarction
Similar for all agents in this class
Pioglitazone, rosiglitazone (had a BBW for over a year, but was removed)
Metformin + sulfonylureas A. Decreased uptake + increased insulin effects B. Proven efficacy, different mechanisms C. Effects not well documented D. Additive GI side effects
B. Proven efficacy, different mechanisms
Metformin + meglitinides
A. Decreased uptake + increased insulin effects
B. Proven efficacy, different mechanisms
C. Effects not well documented
D. For fasting hyperglycemia + for post-prandial sugar
D. For fasting hyperglycemia + for post-prandial sugar
Metformin + thiazolidinediones
A. Decreased uptake + increased insulin effects
B. Useful synergy for reducing insulin resistance
C. Effects not well documented
D. Additive GI side effects
B. Useful synergy for reducing insulin resistance
Acarbose + SUs
A. Decreased uptake + increased insulin effects
B. Useful synergy for reducing insulin resistance
C. Effects not well documented
D. Additive GI side effects
A. Decreased uptake + increased insulin effects
Thiazolidinediones + SUs or meglitinides
A. Decreased uptake + increased insulin effects
B. Useful synergy for reducing insulin resistance
C. Effects not well documented
D. Additive GI side effects
C. Effects not well documented
Analog of gut peptide glucagon-like peptide-1, an “incretin” release in response to food
Exenatide (GLP-1 agonists, Bydureon)
Effects:
Potentiates insulin SECRETION, decreases glucagon, slows gastric emptying, promotes satiety
Exenatide (GLP-1 agonists, Bydureon)
Induces moderate reductions in fasting glucose but marked reductions in post-prandial glucose
Does not cause weight gain…often causes weight loss!
Exenatide (GLP-1 agonists, Bydureon)
Exenatide (GLP-1 agonists, Bydureon)
Exenatide (GLP-1 agonists, Bydureon)
Exenatide cousin approved for weight loss
Liraglutide (Victoza)
ADEs: nausea
Increased risk of hypoglycemia, esp. with SUs
Avoid in renal failure
Exenatide (GLP-1 agonists)
ADEs: alters absorption of some antibiotics and contraceptives, take 1 hour before
Thyroid tumors
Pancreatitis
Exenatide (GLP-1 agonists)
MOA: inhibits dipeptidyl-peptidase IV, the enzyme that degrades endogenous incretins (like GLP-1)
Sitagliptin (Januvia, DDP-IV inhibitors)
Effects- through increasing ENDOGENOUS incretins
Potentiates insulin SECRETION, decreases glucagon, no obvious weight gain or loss
Sitagliptin (Januvia, DPP-IV inhibitors)
Orally effective in once per day monotherapy or in combination
Risk of severe joint pain
Heart failure risk, but only with certain drugs in the class
Sitagliptan (Januvia, DPP-IV inhibitors)
ADEs: increased hypoglycemia risk when used in combo
Increased risk of respiratory tract infections
Renal elimination is a concern in some patients
Sitagliptin (Januvia, DPP-IV inhibitors)
MOA: inhibits sodium-glucose co-transporter 2 (SGLT2), the enzyme that mediates glucose re-absorption in the kidney
Increases urinary glucose excretion
Canagliflozin (Invokana)
Orally effectives, one time daily dosing, usually in the AM
No effects directly on insulin
Concerns about renal injury (with at least some agents)
Cangliflozin (Invokana, SLGT2 inhibitors)
ADEs: increased risk of genital and urinary tract infections
Diuretic effect can cause dehydration, hypovolemia, hypotension (esp. in elderly and those on diuretics)
Fracture risk warning
Cangliflozin (Invokana, SLGT2 inhibitors)
