diabetes drugs Flashcards
what are 5 groups of T2DM drugs?
- metformin (1st line)
- sulphonylureas
- incretin drugs
- SGLT2 inhibitors
- thiazolidinediones
what is mode of action of metformin?
it inhibits gluconeogenesis so lowers hepatic glucose production
*also increases GLP-1 secretion & increases gut glucose utilisation & metabolism
what are side effects of metformin? how can you reduce side effects?
GI intolerance so diarrhoea, bloating, abdo pain and dyspepsia
- normal prescription is 500mg once daily. to help side effects you can initiate slowly with 500mg once a week or modified release formulation
what is mode of action for sulphonylureas?
they act on pancreatic beta cells to increase insulin secretion (insulin secretagogues) = independent of glucose
what is drug example of sulphonylurea?
gliclazide
what is main clinical risk of sulphonylureas? side effects?
hypoglycaemia - they’re glucose independent (meaning can make insulin even if glucose low or normal) so they can just keep lowering & lowering glucose = hypoglycemia risk (means risk for driving, DVLA)
- additional side effect of weight gain as insulin increases appetite
- also maybe increase CV risk but unclear
what is incretin?
incretin is intestinal secretion of insulin
- Glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) are hormones in intestine that work together to increase insulin secretion after eating
*GLP-1 has loads of effects including increasing insulin sensitivity
what have the roles of triggering and amplifying of beta cell production out of sulphonylurea & incretins?
- basically sulphonylureas & glucose trigger the insulin pathway and incretins can amplify
*triggering & amplifying pathways of beta cell via GLP-1 (causes insulin sensitivity)
what are the 2 types of incretin drugs? and examples of each?
- DPP 4 inhibitors e.g. sitagliptin
- GLP-1 receptor agonists e.g. liraglutide (injection) or semaglutide (oral)
what is action of DPP 4 inhibitor? (incretin drug)
weak but smart sulphonylurea like drug = weakly increases insulin secretion by inhibiting breakdown of GLP-1 and GIP
what are side effects of DPP 4 inhibitors? (barely any)
minimal side effects, possible pancreatitis risk
*main good thing = is since incretin glucose dependent they do NOT cause hypoglycaemia
what is GLP-1 receptor agonist mode of action? (incretin drug)
they mimic GLP-1 by binding to GLP-1 receptors and stimulating them (generally more sustained effects on blood glucose)
= promotes insulin secretion in glucose dependent mechanism, also weight loss & CV & renal benefits
what are side effects of GLP-1 receptor agonists?
nausea & vomiting, gallstones, maybe pancreatitis
what is mechanism of action of SGLT2 inhibitors?
inhibit sodium glucose transporter which causes you to pee out glucose & lose calories so weightloss
what is common examples of SGLT2 inhibitors?
dapagliflozin, canagliflozin, empagliflozin
what are some additional complex consequences (good things) for SGLT2 inhibitors?
- has mild diuretic action so good for heart failure (good getting rid of fluid)
- renal protection (through complex mechanism)
- improved myocardial energetics (less glucose means increase in lipolysis to get energy which makes ketone bodies which are good energy for cardiac myocytes)
what are side effects of SGLT2 inhibitors?
- UTI’s & thrush (secondary to glycosuria)
- fournier gangrene (rare infection to genital & perineum)
- hypovolaemia & hypotension
- diabetic ketoacidosis (if too much ketone bodies made then bad)
what is main action of thiazolidinediones?
they target PPAR-gamma receptors in fat cells to help store fat more effectively (increase fat mass so less floating in blood stream) which means better cytokines and less bad ones around. this means increase insulin sensitivity
(only true insulin sensitizer drugs in TD2M)
what is example of thiazolidinediones?
pioglitazone
what are side effects of thiazolidinediones?
- weight gain
- fluid retention = peripheral oedema & doubling risk of hospitalisation for cardiac failure
- fracture risk due to fat accumulation in bone marrow & reduction in bone density
what are 2 drugs improving cardio & renal outcomes?
SGLT2 inhibitors and GLP agonist (incretin drug)
which drug should be avoided if liver & kidney problems?
metformin! = big side effect of lactic acidosis (rare but very important)
- measure kidney function through filtration rate, if filtering rate low (below 25) then avoid metformin
what drug should be avoided in heart failure?
pioglitazone (TZD) as causes fluid overload
what drugs should be stopped if sick?
SGLT2 or metformin
