Diabetes drugs Flashcards
What class of drug is metformin?
Biguanide
Give examples of sulphonylureas
Gliclazide
Glibenclamide
Name a GLP - 1 agonist
Exenatide
Give an example of a DDP - 4 inhibitor
Sitagliptin
Give an example of a thiazolidinedione (TZD)
Pioglitazone
What’s the first line drug for T2DM?
Metformin
Is metformin safe in pregnancy?
Yes!
What effect does metformin have on weight?
Weight loss
How does metformin work?
INCREASE INSULIN SIGNALLING:
Decreases hepatic gluconeogenesis by stimulating AMP-activated protein kinases
Increases glucose uptake by skeletal muscle (by increasing insulin signalling)
Increase fatty acid oxidation
Side effects of metformin?
GI upset
Lactic acidosis
Liver damage and renal toxicity IF GFR IS ALREADY <30ml/min
What’s the risk of using metformin in kidney disease?
lactic acidosis
Can metformin cause hypoglycaemia?
No!
How do sulphonylureas work?
They bind to the SUR1 part of K+ ATP channels in pancreatic beta cells and cause depolarisation.
This results in Ca2+ influx and insulin release
Why can’t SUs be used in T1DM?
They require good beta cell function to work
Can SUs cause hypoglycaemia? Why / why not?
Yes! They close K ATP channels regardless of blood glucose levels
Briefly describe the physiology of insulin release
- Glucose enters beta cells via GLUT2
- It is metabolised by glycolysis / Krebs cycle to form ATP
- An increase ATP:ADP ratio within the cell causes K+ ATP channels to close, resulting in depolarisation (due to increased intracellular K+)
- This allows voltage activated Ca2+ channels to open, causing an influx of calcium into the cell
- Calcium mediated exocytosis of insulin follows
Side effects of sulphonylureas?
HYPOGLYCAEMIA
Weight gain
Headaches
GI upset
Effect of SUs on weight?
Cause weight GAIN
What’s the “reverse tick” effect and which drug class is it associated with?
SUs
They work effectively initially, but efficacy decreases over time
What does GLP stand for (as in GLP1 agonists)? Give another example of an incretin
Glucagon like peptide
Other incretins include GIP
Physiologically, what do incretins (like GLP) do?
Based on that, how do GLP-1 agonists work?
Incretins are released from cells in the small intestine after a meal and stimulate insulin.
This increases cell uptake of glucose and lowers blood sugar.
GLP1 agonists (e.g exenadite) mimic incretins to enhance insulin secretion
Side effects of GLP-1 agonists?
Nausea
Decreased appetite
Very rarely pancreatitis (? and pancreatic cancer)
Effect of GLP-1 agonists on weight?
Weight loss due to decreased appetite
Can GLP-1 agonists cause hypoglycaemia?
No
Physiologically, what does DPP4 do?
Based on this, how do DPP4 inhibitors work?
DPP4 breaks down incretins (such as GLP and GIP).
DPP4 inhibitors prolong the glucose-lowering actions of GLP-1 and GIP.
Side effects of DPP4 inhibitors?
Nausea
Pancreatitis (rare)
Much less potent than GLP-1 agonists - They only work prolonging the action of incretins that are present (and levels are low in T2DM)
Do DPP4 inhibitors (sitaglipin) cause weight loss?
No
How are GLP-1 agonists administered?
SC injection
How do TZDs work?
Enhance the action of insulin at target sites (by acting as exogenous agonists of nuclear receptors)
Act on PPARgamma receptors
(They’re insulin sensitisers)
Side effects of TZDs?
Weight gain
Fluid retention
Increased incidence of bone fractures
(avoid if heart failure, obese or osteoporotic)
Can TZDs cause hypoglycaemia?
Only if used with SUs
How do SGLT2 inhibitors work?
Selectively block reabsoption of glucose by Na / glucose transporters in the proximal tubule, deliberately causing glucosuria and lowering blood sugar
Side effects of SGLT2 inhibitors?
Thrush
UTI
Effect of SGLT2 inhibitors on weight? Risk of hypo?
Weight loss (pee out glucose)
Little risk of hypo
From the following list, which drugs cause weight loss?
Metformin
SUs (gliclazide)
GLP-1 agonists (exenatide)
DPP4 inhibitor (sitigliptin)
PTZ (pioglitazone)
SGLT2 inhibitor (dapagliflozin)
Metformin
GLP-1 agonist
SGLT2 inhibitors
Which of the following cause weight gain?
Metformin
SUs (gliclazide)
GLP-1 agonists (exenatide)
DPP4 inhibitor (sitigliptin)
PTZ (pioglitazone)
SGLT2 inhibitor (dapagliflozin)
SUs
PTZ
Which of the following may cause hypoglycaemia?
Metformin
SUs (gliclazide)
GLP-1 agonists (exenatide)
DPP4 inhibitor (sitigliptin)
PTZ (pioglitazone)
SGLT2 inhibitor (dapagliflozin)
SUs
