Lecture 18 - Medicines for Type 2 Diabetes Flashcards
What type of medicine is metformin?
a biguanide
What is metformin?
first line oral glucose lowering agent for type 2 diabetes
How many people is metformin prescribed to?
83.6% of patients in the UK with type 2 diabetes (2013)
What are the advantages of metformin?
it doesn’t cause weight gain or hypoglycaemia
can be used in overweight patients
When was metformin first used?
1953
What is the most important effect of metformin?
to reduce hepatic glucose production
Mechanism of action of metformin?
still unknown
can affect multiple cellular processes and the most widely accepted is linked to inhibition of mitochondrial respiratory chain-complex 1
How does metformin enter hepatocytes?
through the organic cation transporter 1
What does inhibiton of the complex 1 of the respiratory chain cause?
inhibition of ATP synthesis
increase in AMP
activation of AMPK
phosphorylation and inhibition of CRTC2
inhibition of gluconeogenic gene expression
What is CRTC2?
a transcription factor that normally plays a role in transcription of genes involved in gluconeogenesis so when blocked it leads to decreased synthesis of genes and reduction in glucose production
Side effects of metformin?
GI effects such as diarrhoea, nausea, vomiting, abdominal bloating, reduced appetite
vit B12 deficiency
What % of patients on metformin have a reduced appetite?
20%
What % of patients discontinue metformin use from GI side effects?
5%
How does metformin cause B12 deficiency?
it reduces intestinal absorption of vit B12 in up to 30% of patients and lower serum levels in a dose-dependent manner in 5-10% of patients
What symptoms does B12 deficiency cause?
tiredness and tingling in hands and feet
What is a rare side effect of metformin?
lactic acidosis
Brands of metformin?
bolamyn diagment glucient glucophage metabet
What do sulfonylureas do?
stimulate insulin secretion from pancreatic beta cells
How to sulfonylureas work?
they bind to ATP-gated K+ channels, causing channel closure and membrane depolarisation, which causes calcium to enter the cell and stimulate insulin secretion
Daonil?
glibenclamide
Diamicron, Diamicron MR?
gliclazide
Glibenese, Minodiab?
Glipizide
Amaryl?
glimepiride
Tolbutamide?
tolbutamide
Names of sulfonylureas?
glibenclamide, gliclazide, glipizide, glimepiride, tolbutamide
Side effects of sulfonylureas?
Hypoglycaemia, can also cause weight gain
What are meglitinides?
prandial glucose regulators
Mechanism of action of meglitinides?
similar mechanism to sulfonylureas but rapid onset and short duration
When are meglitinides taken?
before meals
Examples of meglitinides?
repaglinide, nateglinide
Prandin?
repaglinide
Starlix?
Nateglinide
What are thiazolidinediones?
Glitazones
What is the only tablet in the thiazolidinediones?
pioglitazone
How do glitazones work?
increase insulin sensitivity by stimulating the expression of insulin sensitising genes
they are insulin sensitisers
What do thiazolidinediones bind to?
the nuclear receptor PPAR gamma
What does PPAR gamma do?
works with retinoid X receptor to drive the expression of insulin sensitising genes
What are examples of insulin sensitising genes?
GLUT4, PI3 kinase, IRS proteins
Medicines in the thiazolidinedione group?
pioglitazone, and pioglitazone in combination with metformin
Actos?
pioglitazone
Competact?
pioglitazone & metformin
Side effects of thiazolidinediodes?
water retention (oedema) and weight gain
What are GLP-1 analogues?
incretin mimetics
glucagon like peptide 1 analogues that increase insulin release
What is GLP1
glucagon like peptide 1
What happens when GLP1 is released?
following food intake released with GIP, they activate or stimulate insulin release from pancreatic beta cells
GLP and GIP are degraded by?
they have short have lives and are degraded by protease DPP4
Examples of GLP-1 analogues
exenatide, liraglutide, lixisenatide, dulaglutide, semaglutaide
Byetta?
exenatide (twice daily injection)
Bydureon?
exenatide (once weekly injection)
Victoza?
liraglutide (once daily injection)
Lixumia?
lixisenatide (once daily injection)
Trulicity?
dulaglutide (once weekly injection)
Ozempic?
semaglutide (once weekly injection)
What are DPP4 inhibitors?
gliptins
they bind to DPP4 and inhibit its activity, which allows endogenously produced GLP-1 and GIP to accumulate to higher levels and stimulate more secretion of insulin
DPP4 medicines?
sitagliptin, vildagliptin, saxagliptin, alogliptin, linagliptin
Januvia and janumet?
sitagliptin
sitaglipin & metformin
galvus and eucreas?
Vildagliptin
vildagliptin & metformin
Onglyza & Kombolyze?
saxagliptin
saxagliptin & metformin
Vipidia & vipdomet?
alogliptin
alogliptin & metformin
Trajenta & Jentadueto?
linagliptin
linagliptin & metformin
What do alpha glucosidase inhibitor (Acarbose) do?
slow down the absorption of starchy foods by intestine - slows the rise in blood glucose after a meal
What do SGLT2 inhibits do?
act by inhibiting glucose transporter SGLT2, which functions in the kidney to mediate glucose reabsorption, excess glucose is lost in urine
Examples of SGLT2 inhibitors?
dapagliflozin, empagliflozin, canagliflozin
Forxiga?
dapagliflozin
Invokana?
canagliflozin
Jardiance?
empagliflozin
What else is important to control symptoms of type 2 diabetes?
eating a healthy diet and regular exercise
What else may be prescribed if glucose control is not adequate in type 2 diabetes?
Insulin
What has type 2 been discovered as?
A reversible disease
What happens if monotherapy does not work for someone with type 2 diabetes?
an additional oral antidiabetic might be added, can also move to triple therapy if this is not enough
Surgery for diabetes?
~65% of patients with type 2 diabetes were no longer on any diabetic medication 2 years after bariatric surgery
What have NICE recommended with surgery?
all patients in the UK with BMI>35 with recent onset type 2 diabetes should be assessed for surgery
What is the initial cost of surgery?
~£6,000
What else has been shown to put type 2 diabetes into remission?
a very low calorie diet of about 600-700 calories per day
can put diabetes into remission after 4-6 weeks
What is the success of the low calorie diet correlated with?
weight loss - fat loss from pancreas and the liver