incretin drugs Flashcards
where does insulin secretion occur?
the intestines
is the incretin affect lost early or late in T2 diabetes?
early
what are the 2 incretin peptides?
GIP and GLP-1
where does GIP come from?
K cells
Where does GLP-1 come from?
L cells
which enzyme breaks down GIP and GLP-1?
DPP-4
GIP and GLP-1 has a long half life-true or false?
false
very short half life
which pathway do incretins and incretin like drugs act via?
amplifying pathway
are incretins G protein coupled?
yes
what does an increase in cAMP in the amplifying pathway do?
Close KATP channel (PKA)
Modulate calcium currents (PKA)
Directly on Insulin secretory mechanism
what is the main result of incretin drugs
when the pathway is triggered there is augmentation of insulin secretion
NO HYPOGLYCEMIA
GLP-1 leads to
increase in insulin production
which has better insulin secretion-incretin drugs or sulphylureas?
incretin drugs
what are DPP4 inhibitors also known as?
gliptins
what does DPP-4 inhibition lead to?
increased incretin effect
what are the common DPP-4 inhibitors?
alogliptin and saxagliptin
is DPP-4i an insulin secretagogue?
yes
what do DPP-4i inhibit?
GLP-1 and GIP
do DPP4i have a strong or weak glucose lowering?
weak (about 5.8mmol/mol compared to 18mmol/mol)
do DDP4i promote or inhibit weight loss?
Neither! weight neutral
what is the usual drug and dose?
sitagliptin 100mg od
do DPP4i have strong side affects?
no
is there a slight risk of pancreatitis in DDP4i?
yes
what is the impact on DPP4i on CV?
mixed results
-saxagliptin increases risk of HF hospitalisation v placebo, but no overall mortality affect
-no CV risk in sitagliptin
how do GLP-1 receptor agonists work?
the GLP-1 molecule is modified to avoid breakdown by DPP4
do GLP-1 RA act directly or indirectly on the GLP-1 receptor?
directly
how do GLP-1 RA work?
act to promote insulin secretion (so is an insulin secretagogue)
they also lower glucagon (which is increased in T2)
do GLP-1 RA act on other tissues?
yes
hypothalamus to reduce appetite
intestines to reduce gastric emptying
is GLP-1 RA potent?
yes
HbA1c reduction is around 11-15mmol/mol
GLP-1 RA causes wieght gain-true or false?
false
weight loss of 2-3kg
name 2 GLP-1 RA
liraglutide
semaglutide
what is the recommended dose for liraglutide
1.2 mg daily sc
what is the recommended dose for semaglutide?
0.5mg weekly sc
what are the side effects of GLP-1 RA?
nausea and vomiting (usually improves after about 6 weeks)
small increase in chance of gall stones
what other benefits do GLP-1 RA have on other body systems?
CV and renal benefit
