Diabetes Drugs- Metaformin Flashcards
Metformin - Pharmacology
Biguanide
Metformin – site of action (5)
Metformin is hydrophilic so not readily taken up by cells
Requires active transport by Organic Cation Transporters (OCTs)
Distribution of 11C Metformin after oral dosing
concentrated and excreted in (2)
Highly concentrated in the Intestines, Liver and Kidney
Excreted unchanged in the urine (i.e. Metformin is not metabolized)
Metformin – main physiological mechanisms (2)
Lowers Hepatic Glucose Production
(in patients with poorly controlled diabetes)
Increases Gut glucose utilization and metabolism
Metformin – other physiological mechanisms (4)
Increase intestinal GLP-1 secretion
Altered gut microbiome
Decrease Lipogenesis
Reduced inflammation
Metformin – simply (3)
Lowers glucose production and increases glucose utilization
This is ‘similar’ to insulin, but It does this in an ‘insulin independent’ way
Sometimes Metformin is incorrectly termed an ‘insulin sensitizer’ – but it does not increase tissue sensitivity to insulin
Metformin – clinical use (5)
Potent glucose lowering. HbA1c ~18 mmol/mol
Weight neutral or negative (weight losing)
Usual dose 500mg bd; max dose 1g bd
Metformin -side effects (5)
Diarrhoea
Bloating
Abdominal Pain
Dyspepsia
Metallic taste in mouth
Metformin- To reduce side effects GI intolerance
initiate slowly:
Metformin 500mg od 1 week + increase by 500mg od per week
Or
Use a modified release formulation:
Metformin M/R 1g od or 2g od.
Metformin side effects MALA (4)
Metformin Associated Lactic Acidosis (MALA)
Metformin increases lactate production
(esp by the gut and liver)
Lactate is normally cleared by the liver and kidneys
In Acute Kidney Injury metformin is associated with greater risk of Lactic Acidosis.
WHY is metformin 1st line? (4)
its potent
its generally well tolerated
it is weight neutral
probably has CV benefit & very cheap
