hypoglycaemic agents for type 2 DM Flashcards
diagnostic criteria for t2dm
casual plasma glucose/2h post-challenge >/= 11.1 mmol/L
fasting plasma glucose >/= 7.0mmol/L
HbA1c level
biguanide
metformin
insulin sensitiser
oral route
FIRST LINE of therapy for t2dm, low cost
- improves glucose tolerance, lower both basal and postprandial glucose
- high efficiency in lowering HbA1c
- minimal hypoglycaemic risk
high efficiency
mode of action
- v hepatic glucose pdtn
- v intestinal glucose absorption
- ^ density of insulin receptors
- ^ muscular glucose absorption
AE: GIT issues, risk of vit b12 malabsorption – worsen symptoms of neuropathy, risk of lactic acidosis in pt w renal prob
thiazolidinediones
pioglitazone, rosiglitazone
insulin sensitizer
does not affect insulin pdtn
high glucose lowering efficiency
^ insulin-dependent glucose disposal
v insulin resistance in periphery and liver
mode of action
- unclear, mainly through PPAR-gamma activation –> increased pdtn of GLUT 1, GLUT4, increased tissue sensitivity to insulin
AE: weight gain, peripheral edema, increased risk of heart failure (fluid retention), bone fractures
induces CYP450
sulfonylureas
insulin secretagogue – effect dependent on functioning b-cells
high glucose- lowering efficacy, inexpensive
glipizide, gliclazide – lower risk of hypoglycemia
2nd gen: gli-, more potent than first gen (tolbutamide)
mode of action
- SFU targets pancreatic b-cell K- ATP channel, binding inhibits channel mediated K+ efflux, triggering Ca2+ dependent exocytosis of insulin granules
side effects:
weight gain, risk of hypoglycaemia esp in elderly and those w renal/hepatic impairment
contraindication: sulfa allergy
meglitinides
repaglinide, nateglinide
rapid onset, taken right before meal
mode of action
- bind and close K-ATP channels in a glucose-dependent manner stimulating glucose release
- unique binding side diff from SFU
since binding is glucose-dependent, low risk of hypog since insulin low at low glucose
metab by liver – caution for pt w hepatic impairment
alpha glucosidase inhibitor
acarbose, miglitol
must be administered w food
doesn’t affect insulin level/action
not preferred due to lower efficiency and poorer tolerance
mode of action:
- reversibly inhibit membrane-bound alpha-glucosidase in intestinal brush borders
side effects: gaseous distention, flatulence – more CHO for bacteria
contraindicated in pt w GIT diseases eg. IBS, and severe renal/hepatic disease
what is incretin
grp of hormones released after eating to augment secretion of insulin in a glucose-dependent manner – no risk of hypoglycaemia
endo incretin
- GIP
- GLP-1
^ both short half life bc of rapid inactivation by dipeptidyl peptidase-4
incretin based therapy
dipeptidyl peptidase 4 inhibitors
GLP-1 receptor agonist
dipeptidyl peptidase 4 inhibitors
sitagliptin, vildagliptin, linagliptin
expensive
intermediate effciency, neutral effect on weight, generally well tolerated
AE: GIT probs, flu-like symptoms, skin rxn
USE W CAUTION for pt w history of pancreatitis (all incretin mimics/exenatide)
vidagliptin – hepatic metab, not to be used in pt w hepaic impairment
linagliptin – no dose adjustment in pt w chronic liver disease
GLP-1 receptor agonist
liraglutide, semaglutide
VV expensive
high- v high glucose-lowering efficacy, low risk of hypog, intermediate to high weight loss
liraglutide – weight loss
cardioprotective effects of GLP-1 receptor agonists
AE: GIT probs
USE W CAUTION for pt w history of pancreatitis (all incretin mimics/exenatide)
SGLT2 inhibitors
empahliflozin, canagliflozin, dapagliflozin
low risk of hypog
intermediate to high glucose lowering efficacy
reduces renal tubular glucose reabsorption
effect dependent of eGFR
cardiorenal protective effects
AE: UTI, increased urination, female genital mycotic infections, increased risk of lower limb amputation, diabetic ketoacidosis
