Drugs

Question 1

What is type 2 diabetes characterised by?

Answer 1

Characterised by increased insulin resistance of peripheral tissue
Impaired insulin release by beta cells in the pancreas
Decrease in number of or efficient insulin receptors

Question 2

Key symptoms of type 2 diabetes

Answer 2

Polyuria
Polydipsia
Fatigue
Weight loss

Question 3

Which organ do each of the diabetes drug target?

Answer 3

Pancreas (insulin release)
Sulfonlyureas
Insulin secretagogues
DPP-4 inhibitors (gliptins)
GLP-1 agonists

Muscle (increase glucose uptake) &
Liver (reduce glucose production)
metformin
pioglitazone

Pancreas (decrease glucagon release)
DPP-4 inhibitors (gliptins)
GLP-1 agonists

Kidney (reduce glucose absorption)
SGLT-2 inhibitors

Question 4

Metformin Type 2 diabetes

Answer 4

Metformin is still generally considered the gold standard for type 2 diabetes
It has no direct effect on the pancreas

Works by
• reducing hepatic glucose production
• inhibiting intestinal absorption of glucose
• increasing glucose utilisation by enhancing the action of insulin at peripheral receptors • increasing glucose uptake by muscles

Needs to be taken with meals

Question 5

Metformin advantages and disadvantages and other considerations

Answer 5

Advantages:
• No weight gain
• Has cardiovascular-protective effects
• Reduces risk of MI and death
• Does not usually cause hypoglycaemia
• Cost-effective & long-term evidence

Disadvantages:
Starting dose is 500mg daily & needs to be titrated up gradually over a period of weeks
Dose is often limited by gastrointestinal side effects
Care if eGFR < 45, avoid if <30 ml/ min/ 1.72m
Risk of lactic acidosis (avoid in renal impairment, shock, severe infection, acute, MI, heart failure, resp failure)

Other considerations:
Withhold if administering contrast dye
Have to stop metformin for quite a lot of things ie surgery

Question 6

Metformin cautions and contra indications

Answer 6

• Elective surgery involving anaesthesia- Should be stopped 48 hours prior, and restarted 48 hours after surgery.

ØRisk factors for lactic acidosis
Ø Caution in chronic stable heart failure (monitor cardiac function)
• concomitant use of drugs that can acutely impair renal function
• avoid in conditions that can acutely worsen renal function, or cause tissue hypoxia.

• Monitor renal function- once a year in normal people ,twice a year in people with risk factors for renal function deteriorations.

Question 7

Sulfonylureas

Answer 7

• Examples
• Short acting: gliclazide (eg high blood sugar caused by steroids)
• Long acting: glimepiride, glibenclamide

• Work by:
• stimulating insulin secretion by acting directly on pancreatic beta cells
• increasing tissue sensitivity to insulin
• requires residual beta cell function

• Place in therapy
• first line for patients who are not overweight or in whom metformin is contra-indicated or where a rapid response to therapy is required because of hyperglycaemic symptoms

Question 8

Sulfonylureas side effects and contra indications

Answer 8

Side effects
Weight gain
Generally well tolerated, however can cause GI disturbances.
Liver function impairment
Increased risk of hypoglycaemia

Contraindications:
Severe renal/hepatic impairment

Question 9

Sulfonylureas advantages and disadvantages

Answer 9

Eg gliclazide

Advantages
• Choice of agents on the market
• Cost effective & long-term data
• Better than metformin at bringing blood sugars down initially especially of the patient is symptomatic (brings blood sugar down rapidly)

Disadvantages
• Risk of hypoglycaemia (advice patient, driving considerations)
• Care in the elderly, renal & hepatic impairment
• Can cause weight gain

Question 10

Driving advice for diabetics

Answer 10

Tell the DVLA
• on insulin or
• on oral agents and have had 2 episodes of severe hypos in 12 months where you have required someone else to treat you,
• or you have had a disabling hypo whilst driving,
• or are unable to recognise a hypo when it starts.

Question 11

Examples of DPP- 4 inhibitors (gliptins)

Answer 11

linagliptin, saxagliptin, sitagliptin, vildagliptin, alogliptan
• linagliptin is the only renal friendly gliptin and is licensed for monotherapy

Question 12

Action of DPP- 4 inhibitors (gliptins)

Answer 12

Work by:
• inhibiting dipeptidylpeptidase-4 which acts on the GLP1 pathway to increase insulin secretion & lower glucagon secretion

Question 13

DPP- 4 inhibitors advantages and disadvantages

Answer 13

Advantages
• Low risk of causing hypoglycaemia
• Weight neutral

Disadvantages
• Expensive & lack of long-term data
• MHRA reports of pancreatitis & liver toxicity (stop drug if abdo pain occurs)
• Hypersensitivity reactions reported (SJS)
• Dose adjustments in renal impairment
• except linagliptin (excreted in bile)

Side effects:
Sneezing and headaches

Question 14

GLP-1 Agonists examples

Answer 14

exenatide, liraglutide, lixisenatide,semaglutide
Subcutaneous injection (looks like insulin pen)

Question 15

GLP-1 agonists

Answer 15

Binds to and activates the GLP- 1 receptor

GLP-1 receptor
• Increase insulin secretion
• Decreases glucagon secretion
• Slow gastric emptying

Question 16

GLP-1 AGONISTS advantages and disadvantages

Answer 16

Advantages
• promotes some weight loss
• minimal hypoglycaemia
• good option for certain occupations (e.g. HGV drivers) as don’t need to stop driving

Disadvantages
• subcutaneous administration
• store in fridge (can be kept at room temp once in use)
• administer one hour before food (exenatide & lixisenaditide)
• nausea and vomiting
• pancreatitis
• caution in renal impairment

Question 17

GLP-1 agonists place in therapy line

Answer 17

• Place in therapy
• 3rd line
• Combination therapy (with metformin and/or sulphonylurea)
• Combination with insulin upon specialist advice

• NICE:
• BMI ≥ 35 if European (or > 30 in other ethnic groups) and has weight related medical problems
• BMI < 35 but are not able to take insulin (i.e., for occupational reasons) or have co- morbidities that would benefit from weight loss
• Only continue if HbA1c concentration is reduced by 1% and weight loss of at least 3% is achieved within 6 months

Question 18

THIAZOLIDINEDIONES “GLITAZONES”
Examples
Action
Side effects
Contraindications

Answer 18

• Pioglitazone

• Agonist of a receptor called PPAR-gamma which enhances
the action of insulin on liver, fat and skeletal muscle by:
• increasing glucose uptake into muscle cells
• reducing insulin resistance
• decreasing hepatic glucose production

Side effects:
• Fluid retention
• Weight gain
• ↑ risk of fractures

Contraindications:
• Heart failure
• Active bladder cancer
• Hepatic impairment

Question 19

THIAZOLIDINEDIONES “GLITAZONES” advantages and disadvantages

Answer 19

Advantages
• a third line option if a patient has not tolerated or had a poor response to the DPP-4 inhibitors
• low hypoglycaemia risk

Disadvantages
• fluid retention therefore weight gain and contra-indicated in heart failure
• slow onset of action
• fracture risk
• bladder cancer risk
• liver toxicity - monitor LFTs

Question 20

THIAZOLIDINEDIONES place in therapy line

Answer 20

• Pioglitazone should only be continued if HbA1c concentration is reduced by 0.5 percentage points within 6 months of starting treatment

• Place in therapy:
• 2nd or 3rd line
• may be useful if hypos a concern (e.g. driving, falls, occupational hazards)
• combination therapy (with metformin and/or sulphonylurea)

Question 21

SLT-2 inhibitors “flozins”
Examples
Action

Answer 21

Example: dapagliflozin, canagliflozin, empagliflozin

Reversibly inhibits sodium-glucose co-transporter 2 (SGLT2)
• reduces glucose re-absorption
• increases urinary glucose excretion

Licensed as monotherapy but NICE suggest dual therapy
• Dapagliflozin can be used as dual therapy or as add on to insulin but not for triple oral therapy
• Canagliflozin can be used as dual/triple therapy and as add on with insulin

Question 22

SGLT-2 INHIBITORS advantages and disadvantages

Answer 22

Advantages
• Promotes weight loss

Disadvantages
• Need good renal function
• Withhold in AKI/GI illness
• Risk of UTIs and candidiasis due to osmotic diuretic seeing out glucose

Question 23

Insulin in type 2 diabetics
Advantages
Disadvantages
Other considerations

Answer 23

Advantages
• established effective drug

Disadvantages
• hypoglycaemia
• weight gain
• subcutaneous dosing

Other considerations
• may be suitable for patients in whom HbA1c is particularly high and/or are on maximum oral hypoglycaemic therapy
• patient suitability for insulin

Question 24

What diabetes treatment should be given to a patient recently diagnosed however has GI upset?

Answer 24

Modified release metformin

Question 25

Type 2 Diabetes treatment for a patient with chronic heart failure and other CVD complications

Answer 25

Offer metformin or metformin MR if GI disturbances

As soon as metformin tolerability is confirmed offer SGLT2 inhibitor “flozin”

If metformin contraindicated with other co morbidities offer SGLT2 inhibitor alone

If persons HbA1c not controlled below individual threshold see further treatment options

Question 26

Insulin pumps

Answer 26

• NICE technology appraisal guidance 151 (for England and Wales)
• Insulin pump therapy is recommended as a treatment option for adults and children
12 years and older with type 1 diabetes mellitus provided that:
• attempts to achieve target haemoglobin A1c (HbA1c) levels (<48) with multiple daily injections (MDIs) result in the person experiencing disabling hypoglycaemia.
or
• HbA1c levels have remained high (that is, at 8.5% [69 mmol/mol] or above) on MDI therapy (including, if appropriate, the use of long-acting insulin analogues) despite a high level of care.
• Children are eligible if
• Multiple daily injections are impractical or inappropriate

Question 27

Insulin administration

Answer 27

Subcutaneous injection of IV
• Always check needle size patient is using
• 4mm
• 5mm
• Omincan or Glucojet

• Suitable sites: abdomen, thighs and buttock
• Avoid back of the arms – risk of injecting into muscle
• Unpredictable absorption
• Hypoglycaemia risk
• Never inject through clothing