TFW -Type 2 Diabetes Flashcards
What is Type 2 Diabetes?
Type 2 diabetes is a chronic metabolic condition characterised by insulin resistance and insufficient pancreatic insulin production, resulting in high blood-glucose levels (hyperglycaemia).
HbA1c more than 48 mmol/mol [6.5%] or random plasma glucose more than 11.1 mmol/L indicates T2D. True/false?
True
State the risk factors for T2D?
- Weight, BMI, obesity, inactivity, age (being over 40, over 25 for south asian), excessive alcohol intake, unhealthy diet
- FH/genetics (6x more likely to get T2D if first degree relative has it – parent, sibling, child). Abdominal obesity
- Ethnicity (2-4x more likely in people of South Asian descent, Chinese and African-Caribbean or Black African descent)
- High blood pressure or high cholesterol5, atypical antipsychotics e.g. Olanzapine.
- Having PCOS – as women with PCOS are often insulin resistant. History of gestational diabetes (T2D in pregnancy
Diabetes is one of the most common chronic diseases in the UK and can occur in all age groups. Its prevalence is increasing, including in children. True/false?
True
List the Macrovascular complications in T2D
cardiovascular disease (CVD) including ischaemic heart disease, stroke disease, and peripheral arterial disease
List the Microvascular Complications in T2D?
diabetic kidney disease, retinopathy, peripheral and autonomic neuropathy.
List foot problems associated with T2D
foot ulcer, deformity, infection, and Charcot arthropathy.
State the metabolic issue associated with T2D
dyslipidaemia, potentially life-threatening hyperglycaemic emergencies (diabetic ketoacidosis and hyperosmolar hyperglycaemic state
List the clinical features of T2D
polydipsia, polyuria, weight loss, tiredness; enuresis, behavioural changes, and impaired growth (in children); signs of acanthosis nigricans (suggesting insulin resistance)
What are the treatment targets for adults with type 2 diabetes?
Offer lifestyle advice and drug treatment(s) to achieve an individualized target HbA1c level, to minimize the risk of long-term complications, depending on the person’s age, preferences, risk of adverse effects, and co-morbidities.
Educate the person about their individual recommended HbA1c target, and encourage measures to achieve and maintain it, where possible.
What is the recommended HbA1c target an individual should maintain when managing T2D on lifestyle including diet management?
48 mmol/mol (6.5%).
What is the recommended HbA1c target an individual should maintain when managing T2D on Lifestyle including diet combined with a single drug not associated with hypoglycaemia (such as metformin
48 mmol/mol (6.5%).
What is the recommended HbA1c target an individual should maintain when on Drug treatment associated with hypoglycaemia (such as a sulfonylurea)
53 mmol/mol (7.0%)
List the major classes of anti-diabetic Therapeutics
- Exogenous insulin
preparations - Inhibitors of glucose
absorption (“starch
blockers”) - Enhancers of glucose
excretion - Insulin secretagogues
- Insulin sensitisers
- Glucagon-like peptide 1
(GLP-1), “incretin”-based
therapies
What is the therapeutic class of Metformin?
Biguanides
What is the therapeutic class of Metformin?
Biguanides
What is the mechanism of action of Metformin
Insulin sensitisers and inhibitors of hepatic glucose production
Activates adenosine 5’-monophosphate-activated protein kinase (AMPK)
Decrease glucose absorption from gut
Increase insulin receptor activity
Is metformin associated with weight gain and hypoglycaemia?
No weight gain/some weight loss; reduces insulin levels and appetite; low risk of hypoglycaemia (monotherapy); reduces lipids and glucagon levels
List the common side effects of Metformin
Abdominal pain; appetite decreased; diarrhoea; gastrointestinal disorder; nausea; taste altered; vitamin B12 deficiency; vomiting
List the rare side effects of Metformin
Hepatitis; lactic acidosis (discontinue); skin reactions
State the first line treatment for T2D recommended by NICE Guidelines
Offer standard-release metformin as initial treatment, unless it is contraindicated.
what should be monitored before and during treatment of T2D with Metformin?
Renal Function
The risk of low vitamin B12 levels increases with higher metformin dose, longer treatment duration, and in patients with risk factors for vitamin B12 deficiency, including the elderly and people with gastrointestinal disorders such as Crohn’s disease. True/false?
True
Manufacturer advises avoid Metformin if eGFR is less than 30 mL/minute/1.73 m2 In adult. True/false?
True
Healthcare professionals are advised to check serum-vitamin B12 levels if deficiency is suspected in patients on Metformin and consider periodic monitoring in patients with risk factors for deficiency. True/False?
True
What antidiabetic should be offered to a patient if they have a chronic heart failure or established atherosclerotic cardiovascular disease?
Offer an SGLT-2 inhibitor with proven cardiovascular benefit in addition to metformin
What to do when starting an adult with type 2 diabetes on dual therapy with metformin and an SGLT-2 inhibitor as first-line therapy?
introduce the drugs sequentially, starting with metformin and checking tolerability. Start the SGLT-2 inhibitor as soon as metformin tolerability is confirmed.
State the dose of Standard release Metformin in Type 2 diabetes mellitus [monotherapy or in combination with other antidiabetic drugs (including insulin)]
Initially 500 mg once daily for at least 1 week, dose to be taken with breakfast, then 500 mg twice daily for at least 1 week, dose to be taken with breakfast and evening meal, then 500 mg 3 times a day, dose to be taken with breakfast, lunch and evening meal; maximum 2 g per day.
State the dose of modified release Metformin in T2D?
Initially 500 mg once daily, then increased if necessary up to 2 g once daily, dose increased gradually, every 10–15 days, dose to be taken with evening meal, alternatively increased to 1 g twice daily, dose to be taken with meals, alternative dose only to be used if control not achieved with once daily dose regimen. If control still not achieved then change to standard release tablets.
State the mechanism of action of metformin
Metformin exerts its effect mainly by decreasing gluconeogenesis and by increasing peripheral utilisation of glucose; since it acts only in the presence of endogenous insulin it is effective only if there are some residual functioning pancreatic islet cells.
If metformin is contraindicated or not tolerated, consider initial treatment with one of the following, unless contraindicated
- A dipeptidyl peptidase-4
inhibitor (DPP-4 inhibitor),
Pioglitazone,- A sulfonylurea, or
- A sodium-glucose
cotransporter-2 inhibitor
(SGLT-2 inhibitor) may be
considered instead of a
DPP-4 inhibitor, if a
sulfonylurea or
pioglitazone is not
appropriate.
If first-line treatment is ineffective, consider one of the following second-line treatment options for people who can take metformin
- Metformin plus a DPP-4
inhibitor, or
2.Metformin plus
pioglitazone, or - Metformin plus a
sulfonylurea. - Metformin plus an SGLT-2
inhibitor may be
considered if a sulfonylurea
is contraindicated or not
tolerated, or the person is
at significant risk of
hypoglycaemia or its
consequences.
Second line tx for patient in which metformin is contraindicated
- A DPP-4 inhibitor plus
pioglitazone, or - A DPP-4 inhibitor plus a
sulfonylurea, or - Pioglitazone plus a
sulfonylurea
State the third line treatment option for those who can take metformin
- Triple therapy with
metformin, a DPP-4
inhibitor, and a
sulfonylurea. - Triple therapy with
metformin, pioglitazone,
and a sulfonylurea. - Triple therapy with
metformin, pioglitazone or
a sulfonylurea, and the
SGLT-2 inhibitors
canagliflozin or
empagliflozin. - Triple therapy with
metformin, a DPP-4
inhibitor, and the SGLT-2
inhibitor ertugliflozin, only
if a sulfonylurea or
pioglitazone is not
appropriate. - Starting insulin-based
treatment.
SGLT-2 inhibitor dapagliflozin is recommended only in combination with metformin and a sulfonylurea, not pioglitazone. True/false?
True
State the third line tx for people in whom metformin is contraindicated?
Consider starting insulin-based treatment
State what should be offered If third-line treatment is ineffective, not tolerated, or contraindicated
,glucagon-like peptide-1 receptor agonist (GLP-1) + Metformin + Sulfonylurea – but only for pts with BMI of 35+kg/m2 AND issues associated with obesity OR BMI lower than 35 and don’t want insulin therapy (5mcg BD)
A GLP-1 receptor agonist should only be continued if the person has shown a reduction of at least ……..
11 mmol/mol [1.0%] in HbA1c and a weight loss of at least 3% of initial body weight in 6 months.
What to do when patient starts insulin therapy?
continue to offer metformin for people without CI or intolerance, but other antidiabetics reviewed and stopped if needed
What is the mode of action of DPP-4 Inhibitor?
Inhibits dipeptidylpeptidase-4 to increase insulin secretion and lower glucagon secretion.
list examples of drugs in DDP-4 Inhibitor therapeutic class
Alogliptin, Sitagliptin, Linagliptin, Saxagliptin, Vildagliptin
What is the dose of Alogliptin indicated for T2D?
25mg OD
What is the dose of Linagliptin indicated for T2D?
5mg Once daily
What is the dose of sitagliptin indicated for T2D
100mg once daily
What is the dose of saxagliptin for T2D?
5 mg once daily
What is the dose of Vildagliptin indicated for T2D?
50 mg twice daily, reduce dose to 50 mg once daily in the morning when used in dual combination with a sulfonylurea.
What is the common side effect of Vildagliptin?
Dizziness
State the uncommon side effect of Vildagliptin?
Arthralgia; constipation; headache; hypoglycaemia; peripheral oedema
What is the common side effect of Sitagliptin?
Headache
Uncommon side effect of Sitagliptin?
Constipation; dizziness; skin reactions
What is the uncommon side effect of Linagliptin?
Cough; nasopharyngitis
What is the common side effect of Saxagliptin?
Abdominal pain; dizziness; fatigue; headache; increased risk of infection; skin reactions; vomiting
What is the uncommon side effect of Saxagliptin?
Pancreatitis
List drugs in the therapeutic class Sulfonylurea
Gliclazide, Glipizide, Tolbutamide, Long acting -Glibenclamide, Glimepiride
What is the mechanism of action of sulphonylurea
The sulfonylureas act mainly by augmenting insulin secretion and consequently are effective only when some residual pancreatic beta-cell activity is present; during long-term administration they also have an extrapancreatic action.
What is the dose of Gliclazide(immediate release medicine)
Initially 40–80 mg daily,
adjusted according to response, increased if necessary up to 160 mg once daily, dose to be taken with breakfast, doses higher than 160 mg to be given in divided doses; maximum 320 mg per day
What is the dose of Modified release Gliclazide?
Initially 30 mg daily,
dose to be taken with breakfast, adjust dose according to response every 4 weeks (after 2 weeks if no decrease in blood glucose); maximum 120 mg per day.
What is the dose of Glipizide?
Initially 2.5–5 mg daily,
adjusted according to response, dose to be taken shortly before breakfast or lunch, doses up to 15 mg may be given as a single dose, higher doses to be given in divided doses; maximum 20 mg per day
What is the dose of Glimepiride?
Initially 1 mg daily,
adjusted according to response, then increased in steps of 1 mg every 1–2 weeks, increased to 4 mg daily, dose to be taken shortly before or with first main meal, the daily dose may be increased further, in exceptional circumstances; maximum 6 mg per day
What is the dose of Tolbutamide?
0.5–1.5 g daily in divided doses,
dose to be taken with or immediately after meals, alternatively 0.5–1.5 g once daily, dose to be taken with or immediately after breakfast; maximum 2 g per day.
What are the common side effects of sulphonylureas
Abdominal pain
diarrhoea, Hypoglycaemia, nausea
what is the uncommon side effect of Sulphonylureas?
Hepatic disorder, Vomiting
state the name of a long-acting Sulphonylurea that has a risk of prolonged hypoglycaemia especially in ELderly patients
glibenclamide, chlorpropamide, glimepiride)
The use of sulfonylureas in pregnancy should generally be avoided because of the risk of neonatal hypoglycemia. True/false?
True
The use of sulfonylureas in breast-feeding should be avoided because there is a theoretical possibility of hypoglycaemia in the infant. True/false?
True
What is the therapeutic class of Pioglitazone?
thiazolidinedione
State the dose of Pioglitazone?
initially 15–30 mg once daily,
adjusted according to response to 45 mg once daily,
review treatment after 3–6 months and regularly thereafter.
In elderly patients, initiate with lowest possible dose and increase gradually.
What is the mechanism of action of Pioglitazone?
reduces peripheral insulin resistance, leading to a reduction of blood-glucose concentration.
Biguanides eg metformin is contraindicated in……
Acute metabolic acidosis (including lactic acidosis and diabetic ketoacidosis)
State cautions for Biguanides
–Risk factors for lactic acidosis
– In chronic stable heart failure
–Prescription potentially inappropriate (STOPP criteria) if eGFR less than 30 mL/minute/1.73 m2 (risk of lactic acidosis)
State when to avoid metformin in renal impairment
if eGFR is less than 30 mL/minute/1.73 m2.
Monitoring parameters in patients taking metformin
Determine renal function before treatment and at least annually (at least twice a year in patients with additional risk factors for renal impairment, or if deterioration suspected
Patients and carers advise for those on Meformin
should be informed of the risk of lactic acidosis and told to seek immediate medical attention if symptoms such as:
dyspnoea, muscle cramps, abdominal pain, hypothermia, or asthenia occur.
Metformin is associated with weight loss and no hypoglycemia. True/false
True
List drugs in the therapeutic classs of Sodium-glucose co-transporter 2 Inhibitors(SGLT2) (gliflozins)
Dapagliflozin, Empagliflozin, Canagliflozin, Ertugliflozin
What is the mechanism of action of SGLT2?
Reversibly inhibits sodium-glucose co-transporter 2 (SGLT2) in the renal proximal convoluted tubule to reduce glucose reabsorption and increase urinary glucose excretion.
What is the dose of Dapagliflozin in T2D?
10mg once daily
MHRA/CHM advises that there is risk of diabetic ketoacidosis with sodium-glucose co-transporter 2 (SGLT2) inhibitors (canagliflozin, dapagliflozin or empagliflozin). True/false?
True
State To minimize the risk of such effects when treating patients with a SGLT2 inhibitor as MHRA advises?
-inform patients of the signs and symptoms of DKA
-test for raised ketones in patients with signs and symptoms of DKA, even if plasma glucose levels are near-normal
-use dapagliflozin with caution in patients with risk factors for DKA
-discontinue treatment if DKA is suspected or diagnosed
-do not restart treatment with any SGLT2 inhibitor in patients who experienced DKA during use, unless another cause for DKA was identified and resolved
interrupt SGLT2 inhibitor treatment in patients who are hospitalised for major surgery or acute serious illnesses; treatment may be restarted once the patient’s condition has stabilized
What is Fournier’s gangrene?
a rare but serious and potentially life-threatening infection, has been associated with the use of sodium-glucose co-transporter 2 (SGLT2) inhibitors
State the signs of Fournier’s gangrene that patients should be advised to seek medical attention when on SGLT
pain, tenderness, erythema, or swelling in the genital or perineal area, accompanied by fever or malaise—urogenital infection or perineal abscess may precede necrotising fasciitis.
Dapagliflozin is contraindicated in….
Diabetic ketoacidosis
Use Dapagliflozin in which patient group?
Elderly (risk of volume depletion); hypotension; raised hematocrit; risk of volume depletion(Correct hypovolaemia before starting treatment).
State the common or very common side effect of Dapagliflozin
Back pain; balanoposthitis; diabetic ketoacidosis (discontinue immediately); dizziness; dyslipidaemia; hypoglycaemia (in combination with insulin or sulfonylurea); increased risk of infection; rash; urinary disorders
State the uncommon side effect of Dapagliflozin
Constipation; dry mouth; genital pruritus; hypovolaemia; thirst; vulvovaginal pruritus; weight decreased
What is the rare or very rare side effect of Dapagliflozin?
Angioedema; Fournier’s gangrene (discontinue and initiate treatment promptly)
Is Dapagliflozin suitable for Breastfeeding and pregnancy?
Avoid
Is Dapagliflozin suitable for Breastfeeding and pregnancy?
should be avoided
Dose reduction of Dapagliflozin in renal impairment ……
Initially 5 mg daily in severe impairment, increased if tolerated to 10 mg daily.
Avoid initiation if eGFR less than 15 mL/minute/1.73 m2 when treating patient with Dapagliflozin. True/False?
True
Consider additional antidiabetic drugs with dapagliflozin if eGFR less than 45 mL/minute/1.73 m2 (reduced efficacy). True/false
True
State the dose of Empagliflozin for T2D?
10 mg once daily,
increased to 25 mg once daily if necessary and if tolerated.
What is the dose of Ertugliflozin?
5 mg once daily; increased to 15 mg once daily if necessary and if tolerated, dose to be taken in the morning.
State the common side effect of Ertugliflozin
Hypoglycaemia (in combination with insulin or sulfonylurea); hypovolaemia; increased risk of infection; polydipsia; thirst; urinary disorders; vulvovaginal pruritus
All SGLT must be avoided in pregnancy and breastfeeding . True/False?
True
state when Ertugliflozin should be avoided in renal impairment
Avoid initiation if eGFR less than 60 mL/minute/1.73 m2.
Frequent monitoring of renal function required if eGFR less than 60 mL/minute/1.73 m2.
Avoid if eGFR is persistently less than 45 mL/minute/1.73 m2.
monitoring requirement for patients on SGLT
Manufacturer advises to determine renal function before treatment and periodically thereafter.
Manufacturer advises monitor volume status and electrolytes during treatment in patients at risk of volume depletion.
Renal impairment prescribing when on Dapagliflozin
Consider additional antidiabetic drugs with dapagliflozin if eGFR less than 45 mL/minute/1.73 m2 (reduced efficacy).
