6.1.2 Diabetes Type II Flashcards
How does insulin resistance develop?
Initially overcome by increased pancreatic insulin secretion
Insulin receptors then begin to decline
Decreased GLP-1 secretion in response to oral glucose
Reduced response at B cells, eventually insulin production reduced
How is T2DM managed?
Lifestyle
Weight loss
Initially non-insulin therapies such as Metformin
Treat comorbidities
What is the difficulty with medical management of T2DM?
Some therapeutics can cause weight gain which can decrease adherence
What are the different classes of T2DM drugs?
Biguanides
Sulphonylureas
Thiazolidinediones
Sodium glucose contransporter inhibitors (SGLT2)
Dipeptidyl peptidase 4 inhibitors
Glucagon like peptide 1(GLP-1) receptor agonists
What is an example of a biguanide?
Metformin
How do biguanides work?
Metformin
Decreased hepatic glucose production by inhibiting gluconeogenesis
Supresses appetite stops you getting biguanide
First line
What are the adverse effects of biguanides?
Metformin
GI upset
Nausea
Vomiting
Diarrhoea
When should you not take biguanides?
Metformin
Excreted unchanged by kidney
stop if eGFR < 30mL/min
Alcohol intoxication
What are the drug to drug interactions with biguanides?
Metformin
ACEi
Diuretics
NSAIDs
(drugs that impair renal function)
Loop and thiazide diuretics as they increase glucose thus reducing metformin action
What is an example of a sulphonylurea? (SU)
Gliclazide
How do sulphonylureas work?
(Gliclazide)
Stimulate B-cell pancreatic insulin secretion by blocking K+/ATP channels
K+ unable to leave, this depolarises the cell causing voltage-gated Ca2+ channels to open
Rise in Ca2+ causes fusion of insulin with the cell membrane, increased secretion of insulin
How do Beta pancreatic cells usually secrete insulin?
Glucose enters the cell via GLUT2 causing an increase in ATP
ATP phosphorylates the K+/ATP channel blocking it, this causes an increase in intracellular potassium leading to cell depolarisation
Voltage-gated Ca2+ channels open
Rise in Ca2+ causes fusion of insulin with the cell membrane, causing secretion of insulin
What are 3 issues with sulfonylureas?
(Gliclazide)
Need residual pancreatic function to work
Weight gain through anabolic effects of insulin
May lead to hypoglycaemia
What are the adverse effects of sulfonylureas?
(Gliclazide)
Nausea
Vomiting
Diarrhoea
Hypoglycaemia- leads to insulin release at low glucose levels
When should you not use sulfonylureas?
(Gliclazide)
Hepatic and renal disease
Caution those at risk of hypoglycaemia
What are the important drug to drug interactions with sulfonylureas?
(Gliclazide)
Other hypoglycaemic agents
Loop and thiazide diruectics as these increase glucose
Give examples of thiazolidinediones (glitazones)
Pioglitazone
Rosiglitazone
-glitazone suffix
How do thiazolidinediones (glitazones) work?
Pioglitazone Rosiglitazone
Increase insulin sensitivity in muscle and adipose
Decreases hepatic glucose output by activating PPAR-gamma in adipose cells
Increased gene transcription
What are some problems with thiazolidinediones (glitazones)?
Pioglitazone Rosiglitazone
Half-life not related to duration of action, it takes 6-8 weeks for benefit
Weight gain due to fat cell differentiation
What are the adverse effects of thiazolidinediones (glitazones)?
Pioglitazone Rosiglitazone
GI upset
Fluid retention
Fracture risk
Bladder cancer
Due to bladder cancer risk, used less frequently
When should glitazones not be used?
Pioglitazone Rosiglitazone
Heart failure due to fluid retention
What are the important drug to drug reactions with glitazones?
Pioglitazone Rosiglitazone
Other hypogylcaemic agents
What are some examples of sodium-glucose co-transporter inhibitors? (gliflozins)
Dapagliflozin
Canagliflozin
-gliflozin suffix
CD as in loop of henle
How do SGLT-2 inhibitors (gliflozins work)?
Dapagliflozin Canagliflozin
Competitive reversible inhibition of SGLT2 in PCT
Decreases glucose absorption from tubular filtrate, increases urinary glucose excretion
What is good about SGLT2 inhibitors (gliflozins)?
Dapagliflozin Canagliflozin
Weight loss
Low hypogylcaemic risk
When are SGLT2 inhibitors (gliflozins) used?
Dapagliflozin Canagliflozin
Add on therapy
Sometimes used as a monotherapy
HFrEF
CVD risk patients with metformin
What are the adverse effects of SGLT2 inhibitors (gliflozins)?
Dapagliflozin Canagliflozin
UTI
Genital infection
Thirst and polyuria
(Pancreatitis?)
Warnings/contraindications of SGLT2 inhibitors (gliflozins)
Dapagliflozin Canagliflozin
Hypovolaemia- possible hypotension
What are some important drug to drug interactions with SGLT2 inhibitors (gliflozins)?
Dapagliflozin Canagliflozin
Antihypertensives
Other hypergylcaemic agents
What are the physiological effects of GLP-1 (glucagon like peptide) on different organs?
Pancreas
Increased insulin synthesis and secretion (glucose dependent)
Decreased glucagon secretion
Brain
Decreased food intake through increased satiety
Liver (indirect)
Decreased glucose production
Stomach
Decreased gastric emptying
Muscle (indirect)
Increased glucose uptake
Give examples of Dipeptidyl peptidase-4 inhibitors (gliptins)
Sitagliptin
Saxagliptin
-gliptin suffix
How do dipeptidyl peptidase-4 inhibitors (gliptins) work?
Sitagliptin Saxagliptin
Prevent incretin degradation, so plasma incretin levels increase
Suppresses appetite- weight neutral
Why do dipeptidyl peptidase-4 inhibiors (gliptins) have low hypoglycaemic risk?
Sitagliptin Saxagliptin
Glucose dependent, so no stimulation of insulin secretion at normal blood glucose
What are the adverse effects of dipeptidyl peptidase-4 inhibitors (gliptins)?
Sitagliptin Saxagliptin
GI upset
Small pancreatitis risk
When should you not give dipeptidyl peptidase-4 inhibitors (gliptins)?
Sitagliptin Saxagliptin
Pregnancy
Pancreatitis history
What are the important drug to drug interactions of dipeptidyl peptidase-4 inhibitors (gliptins)?
Sitagliptin Saxagliptin
Other hypoglycaemic agents
Thiazide like and loop diuretics as they increase glucose concentration
Give some examples of Glucagon-like peptide-1 (GLP-1) receptor agonists (incretin mimetics)
Exenatide
Liraglutide
Semaglutide
-tide suffix
How do glucagon-like peptide-1 receptor agonists work?
Exenatide Liraglutide Semaglutide
Increases glucose dependent synthesis of insulin secretion from beta cells
Activates glucagon-like peptide-1 receptor- resistant to degradation by dipeptidyl peptidase-4
How are glucagon-like peptidase-1 receptor agonists given?
Exenatide Liraglutide Semaglutide
Subcutaneous injection
What is good about glucagon-like peptide-1 receptor agonists?
Exenatide Liraglutide Semaglutide
Promotes satiety, can lead to weight loss
When are glucagon-like peptide-1 receptor agonists used?
Exenatide Liraglutide Semaglutide
If triple therapy is ineffective
What are the adverse effects of glucagon-like peptide-1 receptor agonist?
Exenatide Liraglutide Semaglutide
GI upset
Decreased appetite with weight loss
When should glucagon-like peptide-1 receptor agonists not be used?
Exenatide Liraglutide Semaglutide
Renal impairment
What are the important drug to drug reactions of glucagon-like peptide-1 receptor agonists?
Exenatide Liraglutide Semaglutide
Other hypoglycaemic agents
How can we reduce GI upset of drugs treating diabetes?
Modified release preparations
Results in fewer GI effects, less frequent dosing and imrpoved adherence
Why must you swallow extended-release tablets whole?
Coating makes the tablet extended release
Without the coating the tablet will not be slow releasing
