Diabetic drugs Flashcards
What is Metformin?
A hydrophilic biguanide - the first line treatment for T2DM
What is the 3 physiological mechanisms of Metformin?
- Lowers hepatic glucose production
- Increases intestinal GLP-1 secretion
- Decreases lipogenesis + fat production in the liver
What are the main side effects of Metformin?
Gastrointestinal intolerance - diarrhoea, bloating, pain etc.
Metformin associated lactic acidosis - in acute kidney injury
What is the pharmacological effects of SGLT2 inhibitors?
Sugar secreted in urine - roughly 2500kcal lost a week due to this
What is the main physiological effect of SGLT2 inhibitors?
Increases renal glucose loss
What is inhibited by SGLT2 inhibitors?
Renal sodium glucose transporter 2
What are dapagliflozin, canagliflozin and empagliflozin examples of?
SGLT2 inhibitors
What are the main side effects of SGLT2 inhibitors?
Genital mycotic infection
Diabetic Ketoacidosis
Hypovolaemia
Hypotension
Fournier gangrene - rare but severe
What 2 diabetic medications should be omitted in acutely unwell patients?
Metformin and SGLT2 inhibitors
What are Thiazolidinediones? What are their pharmacological effect?
They are PPAR gamma ligands that bind to and activate PPAR gamma, forming a complex with co-activator
This results in transactivation of many target genes, some beneficial and some adverse
What do thiazolidinediones ultimately lead to?
Increased insulin sensitivity
What are the main effects of thiazolidinediones on adipocytes?
They increase differentiation from pre-adipocytes to adipocytes, increases subcutaneous fat mass storage
What is ‘lipid steal’ and what class of drug is it a result of?
‘Lipid steal’ is when FFA uptake removes fat from liver and muscle, reducing lipotoxicity.
TZDs
At what point in the treatment of T2DM would you use thiazolidinediones?
As a follow up to metformin when cost is an issue
OR
Used when there is a need to minimise hypoglycaemia in a patient
What are the main side effects of thiazolidinediones?
Weight gain - fat mass increased
Fluid retention
Fracture risk - can be doubled
How do Sulphonylureas work to treat T2DM?
They act on pancreatic beta cells to increase insulin secretion
How can Sulphonylureas cause hypoglycaemia?
They are glucose independent drugs and can secrete insulin when it is not needed - leading to a high insulin concentration and ultimately hypoglycaemia
What is the molecular mechanism of Sulphonylureas?
- Bind to SUR1
- Closure of ATP sensitive K+ channel
- Rise in membrane potential trigger voltage sensitive Ca+ channel
- Calcium influx leads to insulin secretion
What class of drug does gliclazide belong to?
Sulphonylureas
What are the 2 main side effects of sulphonylureas?
- Hypoglycaemia
- Weight gain - due to increased appetite and metabolic effects of the drug
What do Incretin drugs do in the treatment of T2DM?
They act via an amplifying pathway to increase intestinal secretion of insulin when blood glucose levels are high
What are some effects of GLP-1 in the body? (muscle, fat, liver, stomach, heart, brain)
- Increased glucose uptake and storage in muscle and fat
Decreased glucose production from the liver - Increased insulin production and decreased glucagon secretion
- Decreases gastric emptying
- Increases HR and cardiac function
- Decrease appetite
What class of drugs do DPP4 inhibitors belong to?
Incretin drugs
What are DPP4 inhibitors? What do they do?
DPP4 inhibitors are insulin secretagogues that inhibit the breakdown of GLP-1 and GIP
Why will DPP4 inhibitors not cause hypoglycaemia?
Their action is glucose dependent
What are the side effects of DPP4 inhibitors?
Very little - generally well tolerated
May cause an increased risk of pancreatitis
What class of drugs do GLP-1 Receptor Agonists belong to?
Incretin drugs
What do GLP-1 receptor agonists work to do?
Promote insulin secretion in a glucose dependent mechanism and lower glucagon
What class of drugs are liraglutide and semaglutide examples of?
GLP-1 receptor agonists (incretin drugs)
What are the 3 main side effects of GLP-1 receptor agonists?
- Nausea and vomiting
- Gallstones
- Slight chance of pancreatitis
What diabetic drug have been approved for use in obese patients without diabetes?
GLP-1 receptor agonists
What drug classification does Metformin belong to?
Anti-diabetics
What is the mechanism of action of Gliclazide?
Stimulates production and secretion of insulin through the beta cell sulphonylurea receptor, increasing the amount of insulin made by the pancreas.
What is the mechanism of action of Insulin?
Insulin facilitates the passage of glucose across cellular membranes in order to promote glucose uptake in cells.
What is the mechanism of action of Metformin?
Metformin inhibits gluconeogenesis (the synthesis of new glucose) and increasing insulin sensitivity in order to lower blood sugar levels.
