GLP-1 Agonists, DPP-IV Inhibitors, and Amylin Mimetics

Question 1

What is Glucagon-like Peptide (GLP-1) and how are diabetic patients affected?

Answer 1

Incretin hormone
Enhances glucose dependent insulin secretion
Exhibits other anti-hyperglycemic actions once released from the gut
Patients with DM may have lower GLP-1 secretion or impaired response

Question 2

Exenatide (Byetta, Bydureon) and Liraglutide (Victoza) are _____ ______ at the GLP-1 rc.

Answer 2

full agonists

Question 3

What is Dipeptidyl Peptidase IV (DDP-IV)?

Answer 3

An enzyme that rapidly inactivates GLP-1 and GIP (glucose-dependent insulinotropic polypeptide)
Also on surface of multiple cell types that inactivates multiple bioactive peptides

Question 4

Sitagliptan (Januvia) and Saxagliptan (Onglyza) are ____, _____, _____ DPP-IV inhibitors

Answer 4

potent, selective, reversible

Question 5

Exenatide (Byetta, Bydureon) and Liraglutide (Victoza) MOA:

Answer 5

GLP-1 Agonists
Increases insulin secretion by beta pancreatic cells
Glucose-dependent
Suppresses secretion of glucagon by alpha cells (=dec. glucose production)
Slows gastric emptying
Increases satiety, decreases appetite

Question 6

What other benefit besides BG control could Exenatide (Byetta, Bydureon) and Liraglutide (Victoza) have?

Answer 6

Weight loss

Question 7

How are Exenatide (Byetta, Bydureon) and Liraglutide (Victoza) admistered and how are they different from endogenous GLP-1?

Answer 7

SubQ

They are resistant to degradation by DPP-IV (just agonist at same rc as GLP-1, not structurally similar to it)

Question 8

The GLP-1 agonist Bydureon is dosed how often?

Answer 8

Once weekly

extended release formulation of exenatide which is usually only has a half life of 2.4hrs

Question 9

Which GLP-1 agonist would not require dose adjustment in renally impaired patients?

Answer 9

Liraglutide (Victoza)

Question 10

AE of GLP-1 agonists include:

Answer 10

Exenatide (Byetta, Bydureon) and Liraglutide (Victoza)

N/V/D
**Pancreatitis
Hypoglycemia (low risk)

Question 11

DDP-IV inhibitors Sitagliptan (Januvia), Saxagliptan (Onglyza), and Linagliptin (Tradjenta) MOA:

Answer 11

Decreases degradation of endogenous GLP-1 so..
Increases insulin secretion by beta pancreatic cells
Glucose-dependent
Suppresses secretion of glucagon by alpha cels
Slows gastric emptying
Increases satiety, decreases appetite

Question 12

DDP-IV inhibitors Sitagliptan (Januvia), Saxagliptan (Onglyza), and Linagliptin (Tradjenta) effect on body weight:

Answer 12

Neutral

Question 13

How are DDP-IV inhibitors administered?

Answer 13

PO

Question 14

How is Sitagliptan (Januvia) excreted?

Answer 14

Largely unchanged in the urine

Question 15

How is Saxagliptan (Onglyza) metabolized and why could that be important?

Answer 15

By CYP 3A4 to an active metabolite

Could cause drug interactions and be associated with renal or hepatic concerns

Question 16

AE of DDP- IV inhibitors:

Answer 16

Hypoglycemia (low to none)
URI
HA
Hypersensitivity reaction 
Longterm clinical effects unknown (d/t actions in other areas of the body)

Question 17

When is endogenous Amylin secreted?

Answer 17

Co-secreted with insulin by beta pancreatic cells

Insulin and amylin rise and fall together with complementary actions in regulating circulating nutrient levels

Question 18

How are amylin levels affected in patients with DM?

Answer 18

Absolute or relative amylin deficiency present

Question 19

How does amylin effects glucose?

Answer 19

By slowing gastric emptying and regulating post prandial glucagon and reducing food intake

Question 20

Amylin mimetic, Pramlintide (Symlin), MOA:

Answer 20

Amylin analogue
Slows gastric emptying 
Increases satiety 
Suppresses post prandial glucagon rise 
Glucose dependent 

(No weight gain)

Question 21

How are Amylin mimetics administered?

Answer 21

SubQ

Question 22

AE of amylin mimetics, Pramlintide (Symlin):

Answer 22

Nausea

No hypoglycemia alone but at risk when given with insulin