T2DM Drugs Flashcards
Describe insulin release.
Glucose enters ß-cells through GLUT2
Glucose phosphorlyates to glucose-6-phosphate in cytoplasm by glucokinase increasing ATP:ADP ratio
ATP closes KATP channel by acting on Kir6 suninits
(ADP opens channel by acting on SUR1 subunit)
Closure of KATP channel depolarises the cell membrane which opens voltage-gates-Ca channels increasing intracellular Ca
Intracellular Ca releses insulin from secretory vesicles
Is more insulin produced in response to oral glucose of IV glucose.
Why?
Oral glucose produces more insulin
Oral glucose stimulates release of GLP-1 from stomach which amplifies insulin and delays gastric emptying
GLP-1 is quickly inactivated by DPP-4 enzyme
What is the mechanism of action of metformin?
Insulin sensitiser
What is the first line medication in T2DM?
Metformin
What is metformin’s effect on weight?
Can reduce weight
Which T2DM drugs carry a risk of hypoglycamia?
Sulphonylureas
What are some side effects of metformin?
GI upset
Lactic acidosis
What doses of metformin are used?
Start at 500mg
Titrate up to maximal 1000mg BD as needed
If eGFR
What are some contraindications to metformin?
eGFR<30 (CKD G4)
Creatinine>150
Name a sulphonylurea.
Gliclazide
How do sulphonylureas work?
Block ADP binding on KATP channel (SUR1 subunit) which prevents opening of the channel, depolarising the membrane and releasing insulin
(this works independently of glucose and so hypoglycaemia is a risk)
What are some side effects of sulphonylureas?
Weight gain
Headache
What are the indications of sulphonylureas?
Second line add on to metformin
First line if metformin intolerant or contraindicated (poor renal function)
What is pioglitazone?
Thiazolidinedione (TZD) / PPAR-y agonist
How do PPAR-y agonists work?
Bind to transcription factor PPAR-y which alters gene transcription and up regulates insulin action
What are some side effects of PPAR-y agonist?
Fluid retention
Reduced bone density
What are the contraindications to PPAR-y use?
Heart failure
Renal failure
Over 65s (reduced bone density)
What do SGLT-2 inhibitors do?
Inhibit glucose reabsorption resulting in glucose excretion
What are some side effects on SGLT-2 inhibitors?
Thrush
UTI
What are contraindications to SGLT-2 inhibitor use?
Renal failure
Name an SGLT-2 inhibitor.
Dapagliflozin
What are gliptins? How are they administered?
DDP-4 inhibitor
Oral
Name a DDP-4 inhibitor.
Vildagliptin
How do DDP-4 inhibitors work?
Inhibit DDP-4 preventing GLP inactivation which amplifies insulin release
Which of DDP-4 inhibitors and GLP agonists are
- injected and PO?
- more potent and why?
- DDP-4 inhibitors oral and GLP agonists injected
2. DDP-4 inhibitors are less potent as they require endogenous GLP production which is low in T2DM
What drugs are associated with an increased risk of pancreatitis and pancreatic cancer?
GLP agonists
DDP-4 inhibitors
What class of drug is exenatide?
GLP-1 receptor agonist
Name a GLP-1 receptor agonist.
Exenatide
How do GLP-1 receptor agonists work?
Amplify insulin release by acting on GLP-1 receptor
What are GLP-1 receptor agonists effect on weight?
Weight loss via reduced appetite and delayed gastric emptying
Name the injected therapies available to T2DM patients.
GLP-1 receptor agonists
Insulin
Name the 7 drug classes used in T2DM, give an example and its administration route.
Metformin, oral
Sulphonylurea, gliclazide, oral
PPAR-y agonist, pioglitazine, oral
SGLT-2 inhibitor, dapraflozin, oral
DDP-4 inhibitor, vildagliptin, oral
GLP-1 receptor agonist, exenaide, injected
Insulin, injected
