incretin drugs

Question 1

where does insulin secretion occur?

Answer 1

the intestines

Question 2

is the incretin affect lost early or late in T2 diabetes?

Answer 2

early

Question 3

what are the 2 incretin peptides?

Answer 3

GIP and GLP-1

Question 4

where does GIP come from?

Answer 4

K cells

Question 5

Where does GLP-1 come from?

Answer 5

L cells

Question 6

which enzyme breaks down GIP and GLP-1?

Answer 6

DPP-4

Question 7

GIP and GLP-1 has a long half life-true or false?

Answer 7

false
very short half life

Question 8

which pathway do incretins and incretin like drugs act via?

Answer 8

amplifying pathway

Question 9

are incretins G protein coupled?

Answer 9

yes

Question 10

what does an increase in cAMP in the amplifying pathway do?

Answer 10

Close KATP channel (PKA)
Modulate calcium currents (PKA)
Directly on Insulin secretory mechanism

Question 11

what is the main result of incretin drugs

Answer 11

when the pathway is triggered there is augmentation of insulin secretion
NO HYPOGLYCEMIA

Question 12

GLP-1 leads to

Answer 12

increase in insulin production

Question 13

which has better insulin secretion-incretin drugs or sulphylureas?

Answer 13

incretin drugs

Question 14

what are DPP4 inhibitors also known as?

Answer 14

gliptins

Question 15

what does DPP-4 inhibition lead to?

Answer 15

increased incretin effect

Question 16

what are the common DPP-4 inhibitors?

Answer 16

alogliptin and saxagliptin

Question 17

is DPP-4i an insulin secretagogue?

Answer 17

yes

Question 18

what do DPP-4i inhibit?

Answer 18

GLP-1 and GIP

Question 19

do DPP4i have a strong or weak glucose lowering?

Answer 19

weak (about 5.8mmol/mol compared to 18mmol/mol)

Question 20

do DDP4i promote or inhibit weight loss?

Answer 20

Neither! weight neutral

Question 21

what is the usual drug and dose?

Answer 21

sitagliptin 100mg od

Question 22

do DPP4i have strong side affects?

Answer 22

no

Question 23

is there a slight risk of pancreatitis in DDP4i?

Answer 23

yes

Question 24

what is the impact on DPP4i on CV?

Answer 24

mixed results
-saxagliptin increases risk of HF hospitalisation v placebo, but no overall mortality affect
-no CV risk in sitagliptin

Question 25

how do GLP-1 receptor agonists work?

Answer 25

the GLP-1 molecule is modified to avoid breakdown by DPP4

Question 26

do GLP-1 RA act directly or indirectly on the GLP-1 receptor?

Answer 26

directly

Question 27

how do GLP-1 RA work?

Answer 27

act to promote insulin secretion (so is an insulin secretagogue)
they also lower glucagon (which is increased in T2)

Question 28

do GLP-1 RA act on other tissues?

Answer 28

yes
hypothalamus to reduce appetite
intestines to reduce gastric emptying

Question 29

is GLP-1 RA potent?

Answer 29

yes
HbA1c reduction is around 11-15mmol/mol

Question 30

GLP-1 RA causes wieght gain-true or false?

Answer 30

false
weight loss of 2-3kg

Question 31

name 2 GLP-1 RA

Answer 31

liraglutide
semaglutide

Question 32

what is the recommended dose for liraglutide

Answer 32

1.2 mg daily sc

Question 33

what is the recommended dose for semaglutide?

Answer 33

0.5mg weekly sc

Question 34

what are the side effects of GLP-1 RA?

Answer 34

nausea and vomiting (usually improves after about 6 weeks)
small increase in chance of gall stones

Question 35

what other benefits do GLP-1 RA have on other body systems?

Answer 35

CV and renal benefit