"Newer" Non-Insulin Analogues

Question 1

List the 3 “newer” options of non-insulin analogues.

Answer 1

• GLP-1 agonist
• DPP-IV inhibitor
• SGLT2 inhibitor

Question 2

What are incretins?

Answer 2

Gut peptides that modulate insulin secretions in response to nutrients in the bowel

Question 3

GLP-1 Agonist MOA

Answer 3

• Stimulate GLP-1 receptor in incretin system
• **Stimulates insulin secretion, inhibition of glucagon secretion, hepatic glucose production, gastric emptying, and appetite

Question 4

DPP-IV MOA

Answer 4

-Prevent peptide inactivation by DPP-IV –> inc active levels of incretin hormones

Question 5

What are the GLP-1 Agonists? Which is the only PO option?

Answer 5

• Exenatide
• Semaglutide (PO or SC)
• Liraglutide
• Lixisenatide
• Dulaglutide

Question 6

GLP-1 Agonist Indications

Answer 6

• Mono/combo therapy
• Weight loss aid (higher dose liraglutide) w/ diet and exercise
• 10# weight loss at 1 yr
• Approved for pts with or without DM and BMI 30 or higher or 27 or higher and weight-related condition

Question 7

GLP-1 Agonist Pearls

Answer 7

• **Dec A1c 1-1.5%, weight loss/appetite suppression (sema, lira dula, ER exenatide > others)
• Rare hypoglycemia
• **Store in fridge
• Antibodies may develop

Question 8

GLP-1 Agonist Precautions/CI

Answer 8

• CKD
• **Slows gastric emptying–> CI in mod-severe gastroparesis!
• Thyroid issue–> refer to JB

Question 9

GLP-1 Agonist ADRs

Answer 9

• GI intolerance (nausea) IR >ER
• BBW thyroid cancer
• **Acute pancreatitis/pancreatic CA–> monitor high risk pts
• Biliary/GB dz?

Question 10

What are the DPP-IV Inhibitors?

Answer 10

• Sitagliptin*
• Saxagliptin
• Linagliptin*
• Alogliptin

Question 11

DPP-IV Inhibitors Indications

Answer 11

-Mono/combo therapy

Question 12

DPP-IV Inhibitor Pearls

Answer 12

• Dec A1c 0.5-1.0%
• **More effective at reducing postprandial BG than fasting BG
• Weight neutral

Question 13

DPP-IV ADRs

Answer 13

• Caution w CKD
• Hypersensitivity rxn (urticaria)
• **Acute pancreatitis/cancer
• Severe joint pain (rare)

Question 14

You want to put your DMII patient on an SGLT2 inhibitor. Which one will you choose?

Answer 14

Empagliflozin

Question 15

SGLT2 Inhibitor MOA

Answer 15

• SGLT2 is transmembrane protein in kidney

- SGLT2 inhibition dec glucose/Na reabsorption, inc urinary glucose/Na, and dec [BG]/BP

Question 16

SGLT2 Inhibitors Indications

Answer 16

• Mono/combo therapy

- HFrEF

Question 17

When should your patient take their empagliflozin?

Answer 17

Before the first meal of the day

Question 18

A patient is at increased risk of AKI if they are on an SGLT2 inhibitors + what other drugs?

Answer 18

• NSAIDs
• Diuretics
• ACE/ARB
• Monitor renal fcn

Question 19

SGLT2 Pearls

Answer 19

• No hypoglycemia
• Some wt loss
• Dec A1c 0.5-1.0%, dec fasting and post-prandial BG

Question 20

SGLT2 ADRs

Answer 20

• Careful in CKD
• **UTI
• Fournier’s Gangrene
• **Bladder cancer (dapagliflozin)
• Careful using in pts who are high risk for amputation
• **Volume depletion/hypotension
• Inc fracture risk
• **Euglycemic DKA