T2DM Drugs Flashcards
What is increased is T2DM?
increased glucose reabsorption
increased glucagon secretion
increased lipolysis
What is an example of a biguanide
metformin
How does metformin work?
Acts through AMP Kinase and reduces the rate of gluconeogenesis and therefore hepatic output of glucose, by increasing peripheral utilisation of glucose.
It also increases insulin sensitivity.
What is beneficial with metformin?
It does not affect insulin secretion, or induce hypoglycaemia or predispose people to weight gain, making it helpful in people who are overweight.
It also is beneficial in reducing CV risk
What are the unwanted effects of metformin?
Weight loss - anorexia
Diarrhoea (5-10% people cannot use metformin because of this)
Epigastric discomfort
What is the mechanism of action of sulphonyureas?
Act on the SUR receptor on pancreatic beta cells.
This closes ATP sensitive K+ channels and thus potassium efflux.
This causes depolarisation of the cell, and opens voltage gated calcium channel, leading to calcium influx.
Calcium influx is a signal for insulin release
What are the side effects of sulphonyureas?
Hypoglycaemia
Weight gain
Increased cardiovascular mortality/morbidity
Give two examples of sulphonylureas
Tolbutamide
Glicazide
What are meglitinides
These act like sulphonylureas, by acting via the closure of the K+-ATP channel in beta-cells.
These are short acting agents that promote insulin secretion in response to a meal
More expensive than sulphonylureas
Give an example of two meglitinides
Repaglinide
Nateglinide
What is the mechanism of action of thiazolidinediones?
These reduce insulin resistance by interacting with PPAR-gamma. This is a nuclear receptor that regulates genes involved with lipid metabolism and insulin action.
These drugs may act via the glucose-fatty acid cycle, lowering free fatty acid levels promoting glucose consumption by the muscles.
They reduce hepatic glucose production and enhance peripheral glucose uptake.
Give an example of a thiazolidinedione
Pioglitazone
What are the side effects of thiazolidinediones?
Weight gain (5-6kg) Heart failure Fluid retention Increased risk of bladder cancer Osteoporosis
What do GLP-1 hormones do?
Decrease appetite Increase glucose uptake Decrease glucagon release Increase Insulin release Decrease gastric emptying
What does DPP-4 do
Breaks down and inhibits GLP-1
What is the incretin effect?
The idea that incretins cause an increase in insulin after administration of oral glucose more so than IV glucose
What are incretins
Hormones that reduce plasma glucose levels and are released after eating e.g. GLP-1/GIP
Whats the mechanism of action of DPP-4 inhibitors
Inhibit DPP-4 and therefore increase endogenous incretin-mediated increase in insulin secretion
These enhance the incretin effect
Give an example of a DPP-4 inhibitor
Sitagliptin, Sidagliptin, Linagliptin
What are SGLT2 inhibitors
SGLT2 is a channel found in the proximal tubule of the kidney. They function to reabsorb glucose into the cell.
SGLT2 Inhibitors work by reducing the threshold for glucose and increasing the excretion of glucose in the urine
What are the side effects of SGLT2 inhibitors
UTIs
What are GLP-1 agonists
These increase the incretin effect therefore act by increasing insulin secretion, inhibiting glucagon secretion, delaying gastric emptying and having effects on appetite.
Give an example of a GLP-1 agonist
Exenatide
Liraglutide
Give an example of a SGLT2 inhibitor
Empagliflozin
Dapagliflozin
What are the side effects of GLP-1 agonists?
Nausea
Vomiting
AKI
