26 – Other Diabetes Drugs

Sulfonylureas

Tolbutamide
Glyburide
Glipizide
Glimepiride

1. What is an insulin secretagogue? (LP p291)

A drug that insulin secretion

2. Why are insulin secretagogues used only in type 2 diabetes? (LP p291)

3. What are the 3 sulfonylureas most commonly in use today? (LP p291)
•
• Glipizide
• Glimepiride

4. What is the mechanism of action of sulfonylureas? (LP p291)

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5. What pharmacokinetic property makes glyburide, glipizide, and glimepiride more widely-used than
tolbutamide? (LP p291)
Their half-lives allow for dosing

6. What is the primary adverse effect of the sulfonylureas? (LP p291)

7. What drugs commonly interact with sulfonylureas? (LP p293)

• Sulfonamides
•
• Allopurinol

8. What is the expected effect of combining the above drugs with a sulfonylurea? (LP p293)
• Increased risk of
• Make the sulfonylurea

Metformin

9. In what patients does the American Diabetes Association (ADA) recommend using metformin? (LP p297)

10. What is the mechanism of action of metformin? (LP p293)

• Inhibits hepatic
• Improves peripheral glucose uptake
• Affects lipids—modestly lowers LDL and raises HDL

11. When is it dangerous to give metformin? (LP p293)

—metformin stays around longer in the blood, with more potential for side
effects

12. What are the adverse effects of metformin? (LP p293)

• Nausea
• Diarrhea
•

13. What adjustment in metformin dose has to be made in patients with serum creatinine >1.5? (LP p293)

14. What adjustment in metformin dose needs to be made in a patient receiving IV contrast? (LP p293)
for 48 hours after the contrast load

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15. In what other disease is metformin sometimes used? (LP p293)

Thiazolidinediones (TZDs)

16. What two TZDs are still on the market? (LP p294)

17. What is the mechanism of action of the TZDs? (LP p294)

• Ligands of PPAR-γ
• Regulate adipocyte fatty acid production
• Regulate glucose uptake and utilization
• in muscle tissue, liver tissue, and adipocytes

18. What labs need to be monitored when starting a TZD? (LP p294)

19. What are the adverse effects of TZDs? (LP p294)

20. In what disease must TZDs not be used (or used only with extreme caution)? (LP p294)

21. What additional risk is associated with rosiglitazone? (LP p294)

Increased risk of

22. What are the “off-label” uses for TZDs? (LP p295)
• Experimental use for
• (Non-Alcoholic Steatohepatitis)

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Quick Review 1

1. Which anti-diabetic category matches the following side effect? (LP p291-296)

Hypoglycemia
May cause lactic acidosis (rarely)
Contraindicated in moderate to severe CHF
Slightly increases risk of MI
MOA: Stimulate insulin release from beta-cells
MOA: Bind PPAR and increase insulin sensitivity

2. A 60-year-old patient with diabetes mellitus for 10 years is currently taking metformin, glyburide, and
pioglitazone. His HbA1C is 8.5, and he is subsequently started on insulin therapy. What alteration in his oral
diabetic medications should be made?

3. A 35-year-old diabetic female that smokes and is on oral contraceptive pills come to the ER for acute chest
pain with shortness of breath. Physical exam reveals an edematous right ankle, tachypnea, and tachycardia.
It is decided that she needs imaging to rule-out pulmonary embolism. In this patient, why might a V/Q scan
be preferred over CT scan of the chest?

4. What are the contraindications to metformin use? (LP p293)

5. A patient taking glipizide comes to the clinic for hypoglycemia. What is the most appropriate course of action
in this patient?

6. What medication cocktail is commonly seen in older patients with a long history of type 2 DM?
• Diabetic medications
•
• ACE inhibitor
•

7. What is the goal HbA1C in patients with diabetes mellitus?

8. How much should you expect an optimized oral diabetic medication to reduce HbA1C after several months of
use?

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DPP-4 Inhibitors

Sitagliptin
Saxagliptin

1. What are incretin hormones? (LP p295)

Hormones that:
• Stimulate secretion
• Inhibit secretion

2. What is the action of dipeptidyl peptidase-4 (DPP-4)? (LP p295)

3. What is the mechanism of action of DPP-4 inhibitors? (LP p295)

• Inhibit DPP-4
• stay active longer
• insulin and glucagon

4. Are DPP-4 inhibitors used in type 1 or type 2 diabetes? (LP p295)

5. Why must you be careful when using a DPP-4 inhibitor with sulfonylureas? (LP p296)
Increased risk of

6. What dose adjustments need to be made when using a DPP-4 inhibitor in a patient with renal insufficiency?
(LP p295)

7. What are the adverse effects of DPP-4 inhibitors? (LP p296)

Risk of (especially when used with sulfonylureas)

Incretin Mimetics

Exenatide
Liraglutide

8. From what is exenatide derived? (LP p296)

• Synthetic version of
• Found in saliva of Gila monster
• Similar properties to (an incretin hormone)

9. From what is liraglutide derived? (LP p296)

Synthetic analog of
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10. Which incretin mimetic can be dosed once daily? (LP p296)

11. How are the incretin mimetics administered? (LP p296)

12. What are the adverse effects of the incretin mimetics? (LP p296)
•
- Nausea/vomiting
- Diarrhea
- Satiety/anorexia
•
• (rare)
• in rats (liraglutide only)

Other Drugs

Pramlintide Acarbose
Repaglinide Miglitol
Nateglinide

Synthetic Amylin Analog (Pramlintide)

13. What cell type produces the hormone amylin? (LP p290-291)
Produced in the of the pancreas
Released along with

14. How does amylin reduce the body’s demand for insulin? (LP p290-291)
• Delays and improves satiety
• Decreases glucagon secretion

15. How is pramlintide administered? (LP p290-291)

just before meals

16. What are the adverse effects of pramlintide? (LP p290-291)

•
• Anorexia
• Avoid in diabetic gastroparesis

Meglitinides
17. What is the mechanism of action of meglitinides? (LP p292)
•
• Work like sulfonylureas but bind to a different site on the potassium channel

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18. Because of fast onset and short duration of action, when must the meglitindes be taken? (LP p292)

19. What are the adverse effects of the meglitinides? (LP p292)

20. Which drugs interact with the meglitinides? (LP p292)

• of CYP3A4 will reduce meglitinide metabolism and
glucose-lowering effects
- Antifungals (ketoconazole, itraconazole, fluconazole)
- (erythromycin, clarithromycin)
• of CYP3A4 will increase meglitinide metabolism and
glucose-lowering effects
- Carbamazepine
- Rifampin
- Barbiturates

α-Glucosidase Inhibitors
21. What is the mechanism of action of the α-glucosidase inhibitors? (LP p295)
• Inhibit α-glucosidase enzyme in the
• Inhibit to glucose and other sugars

22. What side effects are associated with α-glucosidase inhibitors? (LP p295)

Medications for Hypoglycemia

Glucagon
Diazoxide

23. What are the therapeutic uses for glucagon?

24. What are the therapeutic uses for diazoxide?

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Quick Review 2

1. Which medication should you avoid in patients with gastroparesis? (LP p290-291)

2. Which medications can cause hypoglycemia? (LP p291-296)

• Sulfonylureas
• (Sitagliptin, Saxagliptin)
• Meglitinides (Repaglinide, Nateglinide)

3. Why are the meglitinides not used as often as the sulfonylureas? (LP p297)
• Frequent (30 minutes before eating)
• side effects (abdominal cramping, diarrhea, nausea)

4. Place the following diabetes drugs into their appropriate drug classification. (LP p291-296)
(Pramlintide, Repaglinide, Nateglinide, Acarbose, Miglitol, Exenatide, Liraglutide, Sitagliptin
Saxagliptin)

Synthetic Amylin Analog Meglitinides

, Nateglinide

α-Glucosidase Inhibitors Incretin Mimetics

Acarbose, Exenatide,

DPP-IV Inhibitors
, Saxagliptin

5. Which medications have the positive side effect of weight loss?

and Liraglutide

6. Which medications prevent the breakdown and absorption of glucose? (LP p297)

7. Which medications can have the rare adverse effect of pancreatitis?

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End of Session Quiz

1. Place the following diabetes drugs into the correct category (acarbose, exenatide, glimepiride, glipizide,
glyburide, liraglutide, metformin, miglitol, nateglinide, pioglitazone, pramlintide, repaglinide, rosiglitazone,
saxagliptin, sitagliptin, tolbutamide) (LP p290-297):

Insulin secretagogues Amylin analogues

Insulin sensitizers α-glucosidase inhibitors

Dipeptidyl peptidase-IV inhibitors Incretin mimetics

2. Which of the above medications are classified as thiazolidinediones (TZDs)? (LP p297)

3. Which of the drugs above are given via subcutaneous injection? (LP p290-296)

4. What are the most important adverse effects of: (LP p291-295)

Sulfonylureas

Metformin

Thiazolidinediones (TZDs)

5. Metformin is commonly used as a first-line diabetic medication. What are the contraindications to using
metformin? (LP p293)

6. What is the mechanism of action of exenatide? (LP p296)

7. Which diabetic agents work by delaying the intestinal breakdown and absorption of dietary carbohydrates?
(LP p295)

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8. Which thiazolidinedione is associated with an increased risk of MI? (LP p294)

9. Which diabetic agents require routine monitoring of liver enzymes (AST and ALT)? (LP p294)

10. Which diabetic medications are potentially helpful in treating patients with polycystic ovarian syndrome
(PCOS)? (LP p293)

11. What medication sometimes used to reverse hypoglycemia, can also be used to raise the heart rate in
patients with bradycardia?

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