Diabetes Medication Flashcards
what are the two types of incretin drugs?
DDP4 inhibitors
GLP-1 receptor agonists
describe the incretin effect
when glucose is consumed orally, higher insulin levels are seen than when given IV
shows something else contributing to insulin levels= incretins
when is the incretin effect lost?
early in type 2 diabetes
what do incretins cause?
intestinal secretion of insulin
what are the two types of incretin peptides?
GIP
GLP-1
what breaks down incretin peptides?
the enzyme DPP-4
how are incretin peptides cleared from the body?
converted into inactive metabolites
cleared by the kidneys
name two DPP-4 inhibitors
sitagliptin
alogliptin
how do DPP-4 inhibitors work?
inhibit the breakdown of GLP1 and GIP
do DPP-4 inhibitors carry a risk of hypoglycaemia?
no
they are glucose dependent
how well do DPP-4 inhibitors lower BG?
weak
5-8mmol/mol HbA1c reduction
what effect do DPP-4 inhibitors have on weight?
none
they are weight neutral
what are the side effects of DPP-4 inhibitors?
generally very well tolerated
slight increased risk of pancreatitis
how do GLP-1 receptor agonists work?
modify the shape of the GLP-1 molecule receptor to avoid breakdown by DPP-4
do GLP-1 receptor agonists carry a risk of hypoglycaemia?
no
they are glucose dependent
what do GLP-1 receptor agonists also lower?
glucagon levels
what effects do GLP-1 receptor agonists have on other tissues?
hypothalamus - reduce appetite
intestines - reduce gastric emptying
how well to GLP-1 receptor agonists reduce BG?
potent
HbA1c reduction of 11-15mmol/mol
what effect do GLP-1 receptor agonists have on weight?
weight loss of around 2-3kg
name two GLP-1 receptor agonists
liraglutide
semaglutide
what are the two possible side effects of GLP-1 receptor agonists?
N+V
increased risk of gallstones
although they don’t cause pancreatitis, what effect can GLP-1 receptor agonists have?
sustained increase in pancreatic lipase and amylase
what effect do GLP-1 receptor agonists have on heart disease?
reduce CV mortality
reduce risk of hospitalisation for heart failure
what type of drug is metformin?
a biguanide
what is the first line drug for type 2 diabetes?
metformin
what does metformin need to be taken up by cells and where are these found?
organic cation transporters (OCTs)
intestines, liver and kidneys
how is metformin excreted?
unchanged, by the kidneys
undergoes no metabolism
where is the main site of action of metformin?
the liver
what effect does metformin have in the liver?
lowers hepatic glucose production
what effect does metformin have on the intestines?
increases glucose utilisation and metabolism
increases secretion of GLP-1
what effect does metformin have on BG?
potent lowering of BG
lowers HbA1c by around 18mmol/mol
what effect does metformin have on weight?
usually weight neutral
weight negative in some patients
what is the usual dose of metformin?
50mg twice daily
what is the max dose of metformin?
1g twice daily
what are the two possible side effects of metformin use?
GI intolerance
metformin associated lactic acidosis (MALA)
how can the side effects of metformin be reduced?
initiate the drug slowly
give as a modified release formulation
what are the two glucose transporters found in the renal tubule?
SGLT2
SGLT1
what happens to the renal glucose transporters in diabetes?
they become overwhelmed
glucose is not reabsorbed into the blood, all peed out
what is glycosuria?
glucose in urine
what effect do SGLT2 inhibitors have on the kidneys?
decrease glucose uptake
means some glucose passes straight through and leaves in urine = decreases blood glucose
what effect do SGLT2 inhibitors have on weight?
weight negative
besides lowering BG, what two effects do SGLT2 inhibitors have?
diuretic effect
increased urate excretion
what do SGLT2 inhibitors provide?
some renal protection
what effect do SGLT2 inhibitors have on blood glucose?
moderately lower it
HbA1c reduction of around 11 mmol/mol
what does the glucose lowering effect of SGLT2 inhibitors rely in?
the patients GFR
no benefit if <45
name three SGLT2 inhibitors?
dapagliflozin
canagliflozin
empagliflozin
name four side possible side effects of SGLT2 inhibitors
thrush
gangrene
hypovolemia and hypotension
increased risk of DKA
when should SGLT2 inhibitors be omitted and why?
prolonged fasting or acute illness
due to risks of hypovolaemia and DKA
what does TZD stand for?
thiazolidinediones
what type of drugs are TZDs?
PPARy ligands
how do TZDs work?
bind and activate the transcription factor PPARy, regulating genes
what do TZDs mainly affect?
adipocytes
what effect do TZDs have on the fat stores of the body?
move fat from bad places (around organs) to the subcutaneous area where it is healthier to be
what effect do TZDs have on adipocytes?
cause them to mature and release adiponectin
what is adiponectin?
an insulin sensitizing peptide
what does adiponectin do?
increases insulin sensitivity of the liver
what are TZDs also called?
glitazones
what effect do TZDs have on BG?
potent
15-20mmol/mol reduction
who are TZDs most potent in?
obese women
what effect do TZDs have on weight?
increases weight
what is the available TZD?
pioglitazone
what is the given dose of pioglitazone?
15-30mg once daily
what are the two possible side effects of TZDs?
fluid retention
fracture risk
name four commonly used sulphonylureas
gliclazide
glipizide
glimepiride
glibenclamide
what is the action of sulphonylureas?
act on pancreatic beta cells to increase insulin secretion
is there a risk of hypoglycaemia with sulphonylureas?
YES
they are glucose independent - so cause insulin secretion even when not needed
what effect do sulfonylureas have on BG?
potent glucose lowering
reduce HbA1c by around 18mmol/mol
what effect do sulphonylureas have on weight?
increase by around 1-2kg
what is the most common sulphonylurea in the UK?
gliclazide
what is the starting dose of a sulphonylurea?
40-80mg once daily
what is the max dose of a sulphonylurea?
160mg bd
