Drugs in Endocrinology and Diabetes Flashcards
target blood glucose before meals
4-7mmol/l
target blood glucose after meals
<10mmol/l 2hrs after the meal
When is HbA1C unreliable? (5)
in pregnancy for T1DM diabetes symptoms for less than 2m in acute pancreatic damage haemolysis
Mechanism of Metformin/Biguanides? inhibits hepatic gluconeogenesis
opposes glucagon action
inhibits hepatic gluconeogenesis
opposes glucagon action
side effects of metformin (6)
Anorexia Nausea Diarrhea Weight Loss Vitamin B12 Deficiency Lactic Acidosis
what is the most common initiation drug in T2DM?
Metformin
examples of sulfonylureas
glipizide
gliclazide
tolbutamide
glimepiride
mechanism of sulfonylureas
Close K+ channel in beta-cell membrane so cell depolarizes = insulin release via Ca2+ influx
Side effects of sulfonylureas
hypoglycaemia
diarrhoea
weight gain
deranged LFTs
which is the only glitazone licensed in the UK?
pioglitazone
Mechanism of glitazones/thiazolidinediones
They bind avidly to peroxisome proliferator-activated receptor gamma in adipocytes to promote adipogenesis and fatty acid uptake
modulates genes increasing insulin sensitivity
Onset of pioglitazone
takes about 4 weeks to start working, 8 for full effect
side effects of pioglitazone (7)
weight gain oedema headache anaemia hypoglycaemia altered lipids risk of atypical fractures and heart failure
GLP-1 agonists
Exenatide, liraglutide
Mechanism of GLP-1 agonists
increases glucose dependent insulin secretion, suppresses glucagon secretion
Route of GLP 1 Agonists?
subcutaneous injection
Side effects of GLP-1 agonists (6)
nausea, vomiting, weight loss, pancreatitis, hypoglycaemia, AKI
DPP-4 inhibitors
alogliptin
sitagliptin
vildagliptin
Side effects of DPP-4 inhibitors (3)
pancreatitis
peripheral oedema
GI side effects
SGLT2 inhibitors - list 3
Canagliflozin
Dapagliflozin
Empagliflozin
Mechanism of SGLT2 inhibitors
block glucose reabsorption in PCT
Side effects of SGLT2 inhibitors (5)
weight loss dyslipidaemia dehydration hypotension hypoglycaemia (in combos)
which diabetes drugs come with increased risk of lower limb amputation?
sglt2 inhibitors
Canagliflozin
Dapagliflozin
Empagliflozin
Alpha-glucosidase inhibitors example
acarbose
Mechanism of alpha glucosidase inhibitors
inhibit glucosidases so reduced glucose absorption from gut after carbohydrate meal
Side effects of alpha-glucosidase inhibitors (3)
flatulence, diarrhea, abdominal pain (often poor adherence)
mechanism of meglitinides
closing the ATP-dependent K+ channel in beta cells, stimulating insulin release - basically same as sulfonylureas
benefit of meglitinides
very rapid onset so could be taken just before eating, good for irregular eating
stepwise therapy for T2DM (4)
metformin 1st
dual therapy
triple therapy
consider insulin
Prevalence of gestational diabetes
2-12% of pregnancies
what drug can be used for gestational diabetes?
metformin, all the others to be avoided
driving with diabetes
need to test blood sugar less than 2hrs before start of journey and every 2hrs whilst driving
HbA1c target if on metformin
48mmol/mol
at what HbA1c would you start another drug if patient is on metformin?
58mmol/l
which drug should be added if HbA1c rises to 58?
either a sulfonylurea, a gliptin, pioglitazone or SGLT2 inhibitor
when is triple therapy considered in T2DM?
if HbA1c rises or remains above 58mmol/l on 2 drugs
triple therapy combos in T2DM
- metformin, gliptin, sulfonylurea
- metformin, pioglitazone, sulfonylurea
- metformin, SGLT2i, sulfonylurea
- metformin, pioglitazone, SGLT2i
OR start insulin
criteria for starting a GLP-1 agonist e.g. exenatide in T2DM
triple therapy not working
what needs to happen within 6 months for a patient to continue on exenatide?
need to see effect on HbA1c or at least 3% weight loss
What is considered the first-line hypoglycaemic agent for the treatment of type 2 diabetes mellitus?
Metformin is considered the first-line hypoglycaemic agent for the treatment of type 2 diabetes mellitus.
Metformin has been one of most prescribed medications worldwide over the last decade.
The typical starting dose for adults is … mg daily, which can be increased to a maximum dose of 2 g daily. The most common adverse-effect is gastrointestinal upset (i.e. nausea, abdominal pain, diarrhoea), although rarely metformin can result in lactic acidosis.
Metformin has been one of most prescribed medications worldwide over the last decade.
The typical starting dose for adults is 500 mg daily, which can be increased to a maximum dose of 2 g daily. The most common adverse-effect is gastrointestinal upset (i.e. nausea, abdominal pain, diarrhoea), although rarely metformin can result in lactic acidosis.
Metformin is considered the first-line hypoglycaemic agent for the treatment of type 2 diabetes mellitus. It can be used in combination with other hypoglycaemic agents and with insulin.
Indications include:
Treatment of type 2 diabetes mellitus - Monotherapy or in combination with other anti-diabetic agents
Polycystic ovarian syndrome (PCOS) - to help reduce symptoms of hyperandrogenism (unlicensed indication)
Metformin reduces hepatic glucose production and acts systemically to increase glucose uptake.
Metformin is a biguanide, which is a compound formed by two guanidine molecules. Despite its global use, the exact mechanism of action remains incompletely understood.
Metformin has multiple sites of action. Metformin reduces hepatic glucose production and acts systemically to increase glucose uptake. Metformin does not affect insulin secretion.
Metformin is a…
Metformin is a biguanide,
Suppression of hepatic gluconeogenesis
Within the liver, metformin inhibits the mitochondrial electron transport chain. This leads to activation of the enzyme AMP-activated protein kinase (AMPK). Through other downstream mechanisms, this enhances insulin sensitivity and reduces hepatic glucose output.
Metformin also acts through AMPK-independent pathways by inhibition of the enzyme fructose-1,6-bisphosphatase, which is required for gluconeogenesis. However, risk of hypoglycaemia is minimal as some gluconeogenic activity remains.
GLP-1 is important in glucose homeostasis through numerous mechanisms, including: (4)
GLP-1 is important in glucose homeostasis through numerous mechanisms, including:
Increased insulin secretion
Decreased glucagon secretion
Decreased hepatic glucose output
Increased insulin sensitivity
Dosing of metformin
The general starting dose for adults in 500 mg daily, which can be increased to a maximum of 2g daily.
Metformin should not be used in patients with significant renal impairment (eGFR < 30).
Metformin - most serious adverse effect?
Commonly metformin can cause gastrointestinal upset (i.e. nausea, abdominal pain, diarrhoea). The most serious and well recognised adverse effect, albeit rare, is lactic acidosis.
Absolute contraindications to metformin include…
acute metabolic acidosis.
Metformin should not be used in patients with acute metabolic acidosis (i.e. DKA, lactate acidosis). In addition, metformin should be used with caution in the elderly, particularly those with poor renal function (see below).
Metformin should not be used in patients with acute metabolic acidosis (i.e. DKA, lactate acidosis). In addition, metformin should be used with caution in the elderly, particularly those with poor renal function (see below).
Metformin should not be used in patients with an estimated glomerular filtration rate (eGFR - mL/minute/1.73 m2) or calculated creatinine clearance (CrCl - ml/min) < …
Metformin should not be used in patients with an estimated glomerular filtration rate (eGFR - mL/minute/1.73 m2) or calculated creatinine clearance (CrCl - ml/min) < 30.
Metformin + pregnancy ?
Metformin can be used in diabetes but should be guided by a specialist diabetologist/endocrinologist
Which cells are important for the secretion of the incretin GLP-1?
A K cells B M cells C L cells D D cells E S cells
Incretin hormones are gut peptides that are secreted after nutrient intake.
The key incretin secreted in response to a meal is Glucagon-like-peptide 1 (GLP-1), which is secreted by intestinal L cells.
- K cells: secrete gastric inhibitory peptide (GIP)
- M cells: Specialised epithelial cells of mucosa-associated lymphoid tissue (MALT)
- D cells: Secrete somatostatin
- S cells: Secrete Secretin
Aside from diabetes mellitus, metformin can be prescribed in which other condition? A Migraine B Chronic obstructive pulmonary disease C Hypertension D Polycystic ovarian syndrome (PCOS) E Alcoholic liver disease
D = Polycystic ovarian syndrome (PCOS)
Metformin is prescribed in the treatment of polycystic ovarian syndrome to help reduce symptoms of hyperandrogenism
Which of the following medications can metformin be co-prescribed with?
A Liraglutide B Sitagliptin C Gliclazide D Canagliflozin E All of the above
Metformin is the first-line hypoglycaemic agent used in the treatment of type 2 diabetes, which can be prescribed with all other hypoglycaemic agents.
- Liraglutide: GLP-1 agonist (multiple downstream effects)
- Sitagliptin: DPP-IV inhibitor (inhibis breakdown of GLP-1)
- Gliclazide: short acting sulfonylurea (stimulates release of insulin)
- Canagliflozin: sodium-glucose transport protein 2 (increases urinary glucose excretion)
Metformin may be prescribed as an immediate-release or modified-release preparation.
Which of the following is a common reason for conversion to a modified-release preparation?
A Patient choice B Other hypoglycaemic agent use C Pill burden D Poor absorption E GI side-effects
Modified-release preparations of metformin can be used in patients with GI side-effects
In patients with persistent GI side effects on standard immediate-release preparations of metformin, a trial of modified-release metformin may be used before switching to a different hypoglycaemic agent.
