Oral hypoglycemics 3 - slides 48 to 66

Question 1

What are DPP4 inhibitors?

Answer 1

Dipeptidyl peptidase 4 inhibitors
Peptidase is involved in the breakdown of GLP-1 and GIP as well as several peptides including peptide YY, neuropeptide Y, and growth hormone releasing hormone
Also involved in T-cell activation (CD26)
Serine protrease cleaves two N-terminal amino acids from peptides with proline or alanine in second position

Question 2

What is Sitagliptin?

Answer 2

Competitive DPP4 inhibitor

Question 3

What is Saxagliptin?

Answer 3

DPP4 inhibitor that binds covalently

Question 4

What is Linagliptin?

Answer 4

DPP4 inhibitor that is combined with metformin

Question 5

What is Alogliptin?

Answer 5

DPP4 inhibitor combined with metformin and pioglitazone

Question 6

What is Vildagliptin?

Answer 6

DPP4 inhibitor that binds covalently; requires further studies on renal insufficiency

Question 7

How well do DPP4 inhibitors inhibit DPP4?

Answer 7

They all inhibit DPP4 by > 95%

Question 8

How are DPP4 inhibitors administered?

Answer 8

Oral

Question 9

What can DPP4 inhibitors be combined with?

Answer 9

Can be combined with merformin, pioglitazone, sulfonylureas, and insulin

Question 10

Metabolism of DPP4 inhibitors?

Answer 10

Excreted unchanged in the urine

Question 11

Adverse effects of DPP4 inhibitors?

Answer 11

Few consistent adverse effects
Can see diarrhea, headaches
Angioedema, anaphylaxis, skin rash
Pancreatitis (related to GLP-1)

Question 12

Which combination of drugs was able to reduce A1C by 2.1%?

Answer 12

Sitagliptin 50 mg and Metformin 1000 mg BID

Question 13

Differences between GLP-1 and DPP-4 inhibition:

Enhancing insulin secretion

Answer 13

Same (+++)

Question 14

Differences between GLP-1 and DPP-4 inhibition:

Reducing glucagon

Answer 14

GLP-1 +++

DPP4 Inhibitors ++

Question 15

Differences between GLP-1 and DPP-4 inhibition:

Postprandial hyperglycemia

Answer 15

Same (Reduced in both)

Question 16

Differences between GLP-1 and DPP-4 inhibition:

Gastric emptying

Answer 16

GLP-1 agonist +++

DPP4 Inhib +

Question 17

Differences between GLP-1 and DPP-4 inhibition:

Satiety

Answer 17

GLP-1 agonist +++

DPP4 inhib None

Question 18

Differences between GLP-1 and DPP-4 inhibition:

N/V

Answer 18

GLP-1 agonist +++

DPP4 inhib None

Question 19

Differences between GLP-1 and DPP-4 inhibition:

Appetite suppressed

Answer 19

GLP-1 agonist +++

DPP4 inhib None

Question 20

Differences between GLP-1 and DPP-4 inhibition:

Weight loss

Answer 20

GLP-1 agonist ++

DPP4 inhib: None

Question 21

Differences between GLP-1 and DPP-4 inhibition:

Administration

Answer 21

GLP-1 Injectable

DPP4 Inhib Oral

Question 22

Differences between GLP-1 and DPP-4 inhibition:

Antibody formation

Answer 22

GLP-1 Yes

DPP4 No

Question 23

Differences between GLP-1 and DPP-4 inhibition:

Safety

Answer 23

GLP-1 Worry about pancreatitis

DPP4 Inhib worry about pancreatitis and allergic rxns (SJS)

Question 24

What are alpha-glucosidase inhibitors? What are some examples?

Answer 24

Competitive inhibitors of alpha-amylase and alpha-glucosidase enzymes in intestinal brush border
They decrease postprandial glucose absorption

Examples: Acarbose, Miglitol

Question 25

Comparing Acarbose and Miglitol: Metabolism/excretion?

Answer 25

Acarbose is not absorbed, metabolized by intestinal bacteria Miglitol has saturable absorption, excreted unhanged in kidney

Question 26

Comparing Acarbose and Miglitol: Dosing

Answer 26

Both take with first bite of each meal

Question 27

Comparing Acarbose and Miglitol: Monitoring?

Answer 27

Monitor liver function with Acarbose (can cause elevated liver enzymes)

Question 28

Adverse effects of Acarbose, Miglitol?

Answer 28

Abdominal pain (21%) Diarrhea (33%) - glucose is food for bacteria, bacteria grow Flatulance (77%) - undigested carbohydrates in colon

Question 29

Contraindications for Acarbose, Miglitol?

Answer 29

Inflammatory bowel disease GI obstruction or ulceration Chronic intestinal disease

Question 30

What is Pramlintide?

Answer 30

Islet amyloid polypeptide, secreted by Islet B cells It binds to the amylin receptor in the CNS to decrease stomach emptying, decrease glucagon release, and increase satiety Also lowers insulin requirement (can lower dose of insulin given), can lead to weight loss

Question 31

Pramlintide dosing

Answer 31

SubQ before meals, can be given with insulin but not mixed with insulin (?????)

Question 32

Indications for Pramlintide?

Answer 32

Type 1 and Type 2 diabetes

Question 33

Adverse effects of pramlintide?

Answer 33

Nausea and hypoglycemia

Question 34

Pramlintide excretion?

Answer 34

Kidney

Question 35

What are SGLT2 inhibitors? Example?

Answer 35

Sodium-glucose transporter in the proximal tubule responsible for glucose reabsorption SGLT1 is responsible for glucose uptake in the GI Decreasing serum glucose, increasing weight loss Canagliflozin, dapagliflozin, empagliflozin

Question 36

Cautions with Canagliflozin?

Answer 36

Approval requires post marketing CV outcomes trial, monitoring for pancreatitis, malignancy, hypersensitivity reactions, adverse pregnancy outcomes, and a bone safety study and 2 pediatric studies

Question 37

Adverse effects with Canagliflozin?

Answer 37

``` UTI's Vaginal yeast infections Headache, diarrhea Diuresis Hypoglycemia Decreased intravascular volume leading to orthostatic hypotension ```

Question 38

Cautions with Dapagliflozin?

Answer 38

FDA denied approval in 2012 citing problems with increased bladder and breast cancer risks, UTI and liver damage. Then approved in 2014.

Question 39

Adverse effects of Dapagliflozin?

Answer 39

Contraction of vascular volume Use caution in renal impairment, if you're on loop diuretics, and in elderly Urinary tract infections

Question 40

Adverse effects of Empagliflozin?

Answer 40

Contraction of vascular volume Use caution in renal impairment, if you're on loop diuretics, and in elderly Hypoglycemia can occur with insulin and sulfonylureas UTI's Vaginal yeast infections Increased LDL

Question 41

What is Degludec?

Answer 41

Extended form of insulin B29 I-glutamyl spacer to hexadecanedioic acid, B30 Thr missing 42 hour duration of action Indicated for type 1 and type 2 diabetes Limits nocturnal hypoglycemia Available as injector pen