Oral Anti-diabetic agents

Question 1

MOA: enhances secretion of insulin by beta cells, decreases glucagon production, and increases tissue sensitivity to insulinGlimepiride (sulfonylurea)

Answer 1

Glimepiride (sulfonylurea)

Question 2

How does glimepiride increase the secretion of insulin from beta cells?

Answer 2

By blocking the same ATP-sensitive K+ channels that are blocked by ATP when endogenous glucose is high

Question 3

Administered once-daily with ER formulation or 30 minutes before meals
Metabolized by liver AND kidneys
Contraindication in patients with liver or kidney disease

Answer 3

Glimepiride (sulfonyurea)

Question 4

AEs: hypoglycemia, esp. when given with insulin (not as bad as earlier formulations)
Weight gain
GI/skin/liver/blood abnormalities

Answer 4

Glimepiride (sulfonylurea)

Question 5

Similar mechanism as for SUs, but lower effect
Faster, but shorter action than SUs
Perhaps safer in kidney disease

Answer 5

Meglitinides

Question 6

MOA: targets AMP kinase, a critical regulator of glucose metabolism

Answer 6

Metformin (biguanide, additional liver enzyme targets are being identified or implicated)

Question 7

MOA: effects primarily in the LIVER, decreases glucose production, increases glucose uptake, so makes insulin work better

Answer 7

Metformin (biguanide)

Question 8

T/F: Metformin cannot be used with sulfonylureas, due to the risk of hypoglycemia

Answer 8

False. Different MOAs and metformin does not cause hypoglycemia

Question 9

Administered once-daily with ER formulation or 2-4 times per day after meals
Renal excretion without metabolism (concerns with moderate-severe kidney disease)

Answer 9

Metformin (biguanide)

Question 10

AEs: does not cause hypoglycemia or weight gain
Lactic acidosis
GI effects (metallic taste, diarrhea, nausea, vomiting, anorexia)

Answer 10

Metformin (biguanide)

Question 11

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.

Answer 11

What is lactic acidosis from metformin (biguanide)?

Question 12

Microbial sugars that inhibit sugar metabolizing enzymes, like a-glucosidase and amylase, in the gut

Answer 12

Acarbose

Question 13

MOA: slow formation and absorption of glucose in the gut, by inhibiting hydrolysis of disaccharides and complex carbohydrates

Answer 13

Acarbose

Question 14

Poorly absorbed, remains in the gut

Not a powerful drug. Mainly used in mild disease or with other agents.

Answer 14

Acarbose (decrease glucose formation in the gut)

Question 15

Do not cause hypoglycemia ON THEIR OWN, but with insulin or other oral agents, can increase hypoglycemia risk

Answer 15

Acarbose

Question 16

What do you give someone on acarbose who is hypoglycemic?

Answer 16

Glucose (NOT SUCROSE, or other di+saccharides)

Question 17

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

Answer 17

Acarbose (additive with metformin)

Question 18

MOA: binds and activates peroxisome proliferator-activated receptor-y (PPAR-y), a nuclear transcription factor receptor that enhances transcription of insulin-responsive genes

Answer 18

Pioglitazone, rosiglitazone (thiazolidinediones, TZDs)

Question 19

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

Answer 19

Pioglitazone, rosiglitazone (TZDs)

Question 20

Used for Type 2 insulin resistance
Best taken with food one time daily
Metabolized in liver (safe with renal disease)

Answer 20

Pioglitazone, rosiglitazone

Question 21

AEs: hepatotoxicity and fatal liver disease
CVD/death risk
May increase bladder cancer risk
Increase fracture risk

Answer 21

Pioglitazone, rosiglitazone

Question 22

AEs: dose-dependent edema, increase in CHF, myocardial ischemia, angina, and myocardial infarction
Similar for all agents in this class

Answer 22

Pioglitazone, rosiglitazone (had a BBW for over a year, but was removed)

Question 23

Metformin + sulfonylureas
A. Decreased uptake + increased insulin effects
B. Proven efficacy, different mechanisms
C. Effects not well documented
D. Additive GI side effects

Answer 23

B. Proven efficacy, different mechanisms

Question 24

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

Answer 24

D. For fasting hyperglycemia + for post-prandial sugar

Question 25

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

Answer 25

B. Useful synergy for reducing insulin resistance

Question 26

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

Answer 26

A. Decreased uptake + increased insulin effects

Question 27

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

Answer 27

C. Effects not well documented

Question 28

Analog of gut peptide glucagon-like peptide-1, an "incretin" release in response to food

Answer 28

Exenatide (GLP-1 agonists, Bydureon)

Question 29

Effects: | Potentiates insulin SECRETION, decreases glucagon, slows gastric emptying, promotes satiety

Answer 29

Exenatide (GLP-1 agonists, Bydureon)

Question 30

Induces moderate reductions in fasting glucose but marked reductions in post-prandial glucose Does not cause weight gain...often causes weight loss!

Answer 30

Exenatide (GLP-1 agonists, Bydureon)

Question 31

Exenatide (GLP-1 agonists, Bydureon)

Answer 31

Exenatide (GLP-1 agonists, Bydureon)

Question 32

Exenatide cousin approved for weight loss

Answer 32

Liraglutide (Victoza)

Question 33

ADEs: nausea Increased risk of hypoglycemia, esp. with SUs Avoid in renal failure

Answer 33

Exenatide (GLP-1 agonists)

Question 34

ADEs: alters absorption of some antibiotics and contraceptives, take 1 hour before Thyroid tumors Pancreatitis

Answer 34

Exenatide (GLP-1 agonists)

Question 35

MOA: inhibits dipeptidyl-peptidase IV, the enzyme that degrades endogenous incretins (like GLP-1)

Answer 35

Sitagliptin (Januvia, DDP-IV inhibitors)

Question 36

Effects- through increasing ENDOGENOUS incretins | Potentiates insulin SECRETION, decreases glucagon, no obvious weight gain or loss

Answer 36

Sitagliptin (Januvia, DPP-IV inhibitors)

Question 37

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

Answer 37

Sitagliptan (Januvia, DPP-IV inhibitors)

Question 38

ADEs: increased hypoglycemia risk when used in combo Increased risk of respiratory tract infections Renal elimination is a concern in some patients

Answer 38

Sitagliptin (Januvia, DPP-IV inhibitors)

Question 39

MOA: inhibits sodium-glucose co-transporter 2 (SGLT2), the enzyme that mediates glucose re-absorption in the kidney Increases urinary glucose excretion

Answer 39

Canagliflozin (Invokana)

Question 40

Orally effectives, one time daily dosing, usually in the AM No effects directly on insulin Concerns about renal injury (with at least some agents)

Answer 40

Cangliflozin (Invokana, SLGT2 inhibitors)

Question 41

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

Answer 41

Cangliflozin (Invokana, SLGT2 inhibitors)