Does the patient need insulin?
• Not achieving target HbA1c 50-55 mmol/mol
• 1. Doing as much as possible re diet and exercise
•
•
•
•
Gym membership deals
Advice on food: types and amount
Bariatric Surgery; Optifast
Willingness to change?
• 2. Taking maximum doses of oral medication
•
•
•
•
•
Metformin can be continued until eGFR<30ml/min
Gliclazide 320mg/day; Glipizide 30mg/day
Pioglitazone for young, obese
Don’t forget Acarbose
Drug adherence? Checking with patient and with dispensing
• 3. Is the patient actually primarily insulin
deficient (rather than insulin resistant):
– Suboptimal HbA1c and slim with weight loss
• BMI <= 25;
– Overweight patient with duration of diabetes > 10 years;
previously good glycaemic control on oral agents
• 4. Is the target HbA1c realistic for the patient:
– Frail, elderly, mentally ill: trigger HbA1c for
commencement of insulin may be higher (e.g. HbA1c>
65 mmol/mol)
Type 2 diabetes is a progressive disease that requires
progressive treatment
ß-cell function and insulin secretion progressively decline in
type 2 diabetes
Diagnosis of type 2 diabetes
Is insulin going to be effective?
• 1. How much is the patient prepared to do?
– Testing regularly: need to know the blood glucose
(BG) profile to work out the best insulin regime
– Learning how to self-inject
– Learning how to adjust the doses
• 2. How much are you and your nurse
prepared to do?
– Teaching how to inject
– Supervising titration of dose in a timely manner
– Giving advice on dose adjustment for meal content,
exercise if on multidose regime
Education Required
•
•
•
•
•
•
•
Lifestyle advice; BG monitoring
Use of insulin pens
Injection technique
Insulin action, timing of injections, storage
Disposal of sharps
Hypo management, prevention
Sick day management
How many injections per day?
• How many is the patient prepared to
do?
• How high is the HbA1c? Are the oral
agents providing any benefit?
– Likely if HbA1c is between 55 and 75
mmol/mol:
• Once daily insulin added on to oral agents indicated
– HbA1c > 75: oral agents failing and full
switch to insulin may be best.
Insulin therapy.
Once daily basal insulin
• Glargine (Lantus) vs. Isophane
(Protophane/Humulin NPH)
– NZ Guideline Group (NZGG): Isophane
– Commonly used: Glargine
• Isophane: cheaper, long and safe track
record, 12-18 hours of action
– Protophane: Novo pen; Humulin NPH: Luxura
pen
• i.e. no real difference between the two brands but specific
pen needs to be given
Basal Insulin: provides background
insulin but does not cover meals
Isophane
Glargine
•Schematic action profiles, theoretical representation of insulin injected once a day - results may vary from patient to patient.
Once daily Isophane insulin (Protophane or
Humulin NPH): Indications
• Night dose: Good for patients whose blood sugars climb
overnight but have even control during the day due to
oral agents:
– Continue oral agents and prescribe Isophane insulin
at 8-9pm
• Morning dose: Elderly patients often do not need much
diabetes treatment overnight (reduced hepatic
gluconeogenesis) and also useful for those on
Prednisone mane
– Fasting BG 4-6 but climb during the day
– Continue oral agents and prescribe Isophane insulin
at 8-9am
What are the pros and cons of the Novopen vs.
the Luxura?
• Novopen
– slightly bigger numbers
– its mechanism makes
counting the clicks (for
the sight impaired ) a
little easier.
– need to pull the end out
first before dialing up
• Luxura (Huma Pen)
– heavier
– mechanism feels a little
looser - possibly easier
to make mistakes
– you just dial.
Isophane insulin: Starting Dose
• NZGG suggest 10 units starting dose
– Insulin requirement relates to body weight
– If patient > 50kg, expect the dose will need to
climb
• If patient overweight (BMI > 30) or HbA1c > 65
mmol/mol, suggest start at a higher dose, e.g.
0.2 units/kg body weight/day
– e.g. 100kg patient will likely need at least 20 units
Glargine (Lantus) insulin
• Only funded long-acting insulin analogue (Levemir
not funded)
• Concerns about potential cancer risk have been
disputed
• 24 hour action for approximately 70-80% patients
• Constant insulin profile with no peak action
– can be given at any time of the day so long as
the same time each day
• More sensitive to heat than other insulins
Glargine (Lantus) Insulin
• Given either with disposable pen (Solostar Pen)
or in penfill used in ClikSTAR Pen
– If prescribe Solostar, no need to provide pen and
no need for patient to refill pen, but more waste
• Solostar Pen ready filled and dispensed at
pharmacy
– ClikSTAR pen: satisfactory but not as robust as
NovoPen/Luxura pen:
• Large numbers, easy to see
Once daily Glargine (Lantus): Indications
• 24 hour basal insulin needed: BG high in the
morning and climb over the day
• HbA1c > 65 despite maximum oral agents
• An introduction to insulin for those who really
need full insulin cover but reluctant/unwilling;
more coverage than Isophane
– No need to time Glargine insulin injection with meals
– Still need to cover postprandial hyperglycaemia with
something (oral agents or insulin)
The problem with type 2 diabetes
The mealtime insulin secretory response is blunted…
...resulting in undesired mealtime glucose excursions
Both fasting & mealtime glucose contribute to HbA1c
• Clinical evidence suggests that reducing PPG excursions is as
important, or perhaps more important than fasting blood glucose
(FBG), for achieving HbA1c goals
Oral hpoglycaemic agents
(OHA) and basal insulin
– Tempting to stop all OHA and just have one
injection per day
• Will achieve better control than no treatment
• Can result in worse control if patient was taking
oral medication as prescribed
– Metformin useful agent to continue in most
patients
•
•
•
•
Reduces insulin resistance
Treats post-prandial hyperglycaemia
No hypoglycaemia due to Metformin itself
Continue at same dose
Suphonylureas and basal
insulin
• NZGG:
– Once daily Isophane: continue Sulphonylurea
– Twice daily Isophane: discontinue
Sulphonylurea
– If control just above target HbA1c, then this may work
– But Isophane will not cover post-prandial
hyperglycaemia:
» If HbA1c > 65, continue Sulphonylurea
• Once daily Glargine: similar to twice daily
Isophane
Some typical treatment regimens: OHA and basal
insulin
• Metformin 850mg tds, Gliclazide 160mg
bd, Protophane 15 units nocte
• Metformin 1gm tds, Humulin N 12 units bd
• Gliclazide 80mg tds, Glargine 30 units
daily (renal pt)
Other OHA
• Pioglitazone: usually discontinued at
insulin commencement
– Increased risk of fluid retention
– But…. In young overweight patient maybe
continued to help minimise the insulin dose
• Acarbose: can be continued if useful
Are OHA adding anything?
• If HbA1c > 75 mmol/mol and pt taking the
OHA at maximum doses, then probably
not
• If 2-hour post-prandial BG > 10, then
probably not
– Will depend on pre-prandial BG
• Will need insulin to cover meals……unless
patient can reduce carbohydrates / meal
size
Insulin Mealtime Cover
Rapid-acting insulin
Onset approx 10 minutes after injection.
Duration of action around 1–3 hours.
Rapid-acting insulin should be given immediately
before a meal (or can be given soon after meals)
Brand names: Humalog, NovoRapid, Apidra
Short-acting insulin
Onset approx 30 minutes after injection.
Duration of action around 3-6 hours.
Short-acting insulin should be given 20-30 minutes
before a meal
Brand names: Humulin R, Actrapid
Short acting insulin
– Actrapid and Humulin R not routinely used
•
Can be useful to try and cover both breakfast and
lunch or extended evening food intake
–
E.g. children who do not want to inject at school
–
Adults who eat most of their food in the evening but over an
extended period (probably better in a pre-mixed formulation)
Rapid acting Insulins
• Novorapid vs Humalog vs Apidra
– No significant difference between them
– Novorapid: Novo pen; slightly longer tail of
action, up to 4-5 hours
– Humalog: Luxura pen; action 3-4 hours
– Apidra: disposable solostar pen; action 3-4
hrs
Basal bolus insulin regimes
• Basal insulin (Isophane or Glargine) taken once or twice
daily
• Bolus insulin (Novorapid, Humalog or Apidra) with meals
• Standard regimen for type 1 diabetes
• Becoming popular with insulin requiring type 2 pts
– Most flexible insulin regimen
• But… does require multiple insulin injections per day
– Plus education about adjusting bolus insulin doses for
variable meals
Basal bolus regimens
• Usual: Rapid acting insulin tds + Glargine mane or nocte
• Examples of variations:
– Glargine once daily + Apidra with main evening meal+ Metformin
tds (can give Glargine and Apidra at same time)
• Good for pt who eats large evening meal, snacks during day
– Humulin N mane + Humalog with breakfast and lunch +
Metformin tds
• Pt on Prednisone 10mg mane for PMR
• Can become somewhat complicated!
Pre-mixed Insulins
• Avoid complicated regimens in patients who need more
than basal insulin + OHA
• Cover background insulin requirements + meal cover
• Two injections per day timed with breakfast and evening
meals
– Have to eat at these times
– Good opportunity to stress importance of regular
meals
• Usually continue Metformin but discontinue
sulphonylurea, other OHA
Pre-mixed Insulins: Covering meals and
giving basal cover
•
• A mixture of either rapid or shortacting and intermediate-acting
insulin which act just like two
injections of the separate
components taken at the same
time
• Useful for many type 2 patients
with tablet failure requiring
insulin
Pre-mixed Insulins:
Short acting insulin + isophane
– Penmix 30: 30% Actrapid, 70% Protophane
– Penmix 50: 50% Actrapid, 70% Protophane
– Humulin 30/70: 30% Humulin R, 70% Humulin N
• Ideally injected 20 mins before meal
• Actrapid/Humulin R longer duration of action
– cover breakfast and lunch
– but can linger and potentiate hypoglycaemia overnight
• Most patients use Penmix 30 or Humulin 30
– Penmix 50 useful for big eaters
Pre-mixed Insulins:
Rapid acting insulin + isophane
– Humalog Mix 25: 25% Humalog, 75% Humulin N
– Novomix 30: 30% Novorapid, 70% Protophane
– Humalog Mix 50: 50% Humalog, 50% Humulin N
• Cover breakfast and dinner well, but not lunch
– Inject when meal served or just after
• Most patients use Humalog Mix 25 or Novomix 30:
– Not much difference
– Novomix 30: disposable pen
• Humalog Mix 50 can be useful to cover large evening
meal
Pre-mixed Insulins
•
Pros
– cover overnight hyperglycaemia and
address postprandial excursions
•
•
•
– Humalog Mix/ Novomix:
• Inject at meal-time
•
• Less likelihood pre-prandial
hypoglycaemia
Penmix/Humulin Mix
• Improved cover lunch and late
night snack
•
•
Cons
injections must be given at meal
times; work best if regular time for
breakfast and evening meal
difficult to adjust dose if:
– large variation in carbohdrate
component of meal
– sudden increase in physical
activity
Humalog/Novo Mix
– Not good lunch cover
Penmix/Humulin Mix
– Inject 20 mins before meal
Insulin prescription
• Need to also prescribe insulin pen needles
– We recommend 5mm needle length to ensure
subcutaneous administration (rather than
intramuscular) for most people
• How to get around expected increase of
dose?
– Prescribe higher dose but instruct patient to
start with lower dose? May cause confusion
– Write on script that dose may be increased
and repeats needed early
– Write another script if supplies run out early
Adjusting insulin doses
• The patient should be instructed in adjusting
their own insulin – checking with the practice
weekly.
• 2-4 unit adjustment every 3-4 days until target
blood glucose is reached.
Targets: Pre breakfast target <7.0mmol/L
• 2 hour post meal target <10.0mmol/L
• Pre-dinner target 6.0–7.0mmol/L
Insulin Dosage Adjustments –
Pre-mixed insulin Regime
(on HealthPoint)
Insulin Dosage Adjustments – Basal Bolus Regime
(on HealthPoint)
Blood Glucose Levels
(mmols/litre)
Less than 4 or hypo
4-8
8-15
15 or higher
Reduce
cloudy night time insulin by 2
units
Good
Control
Increase
cloudy night time insulin
by 2 units
Increase
cloudy night time insulin
by 4 units.
Reduce
breakfast insulin by 2 units
Good
Control
Increase
breakfast insulin by 2
units
Increase
breakfast insulin by 4
units
Before evening meal
Reduce
lunch insulin by 2 units
Good
Control
Increase
Lunch insulin by 2 units
Increase
lunch insulin by 4 units
Before bed
Reduce
evening insulin by 2 units
Good
Control
Increase
evening insulin by 2
units
Increase
evening insulin by 4
units
Blood testing times
Before breakfast
Before lunch
Increasing Insulin Doses:
Isophane nocte
• Pre breakfast (fasting) BG
– Usually >8 mmol/L and never less than 4:
• Increase dose by 4–6 units
– Usually 6–8 mmol/L and never less than 4:
• Increase dose by 2–4 units
• Once receiving >20 units daily + 3 consecutive
pre breakfast (fasting) BG results higher than
agreed BG target AND BG never less than 4
mmol/L
– Insulin dose can be increased by 10–20% of total
daily dose
Twice daily Isophane (=
Glargine)
• Pre evening meal BG
– Usually >8 mmol/L and never less than 4
• Increase pre breakfast insulin dose by 4–5 units
• Usually 7–8 mmol/L and never less than 4
– Increase pre breakfast insulin dose by 2–4 units
• Once receiving >20 units daily
– 3 consecutive BG results (either pre breakfast or
pre evening meal) higher than agreed BG target
AND BG never less than 4 mmol/L
– Appropriate insulin dose can be increased by 10–
20% of total daily dose
Post-prandial testing
• Check 2 hours after meal: target BG < 10
– If on OHA, maximise
– If still not meeting target, make sure basal
insulin dose is correct (pre-meal BG < 7)
• If basal insulin correct then need to add rapid
acting insulin or
• Change to Premixed insulin regime
Not testing (or not very much)!
• Difficult to manage accurately
– Most patients will check fasting BG
• At least can adjust basal insulin (unless pt eats
overnight)
– Alternate times of testing so once or twice daily test
can give maximum information; certain days of the
week
• Sometimes pre-prandial, sometimes post-prandial
– Evening meal usually largest so 2 hours after dinner
• Regular HbA1c (2-3 monthly)
HbA1c remains suboptimal
• Is basal insulin enough?
– Is the dose correct: fasting BG < 7
– Some obese patients require large doses of
insulin
• Basal insulin 0.5 units/kg body weight/day
• What about post-prandial
hyperglycaemia?
– It always comes back to the food!
– If basal dose correct and on maximum OHA
• Change to Pre-mixed insulin / basal bolus
Changing Insulin Regimens
• Options if HbA1c suboptimal on basal insulin:
– If not on sulphonylurea: add it on and maximise
– If on once daily Isophane, change to bd or Glargine
– If on maximum orals: change to Pre-mixed bd
insulin
• Stop sulphonylurea, give same insulin dose as
basal
– Isophane 24 units bd: Penmix 30 24 units bd
– Or, continue with basal insulin, stop sulphonylurea
and add rapid acting insulin
• Usually need same total daily dose as basal insulin
• Glargine 30 units daily: Novorapid 10 units tds
When to refer to Secondary
services
• This will depend on your teams’ experience:
– Current situation (from my viewpoint):
• Some practices independently start patients on
insulin
– Refer when issues with hypoglycaemia impact on
improved control.
– Or not achieving any improvement in HbA1c
» Sometimes patients will self-refer
• Other practices refer everyone who is on OHAs
with suboptimal HbA1c
– Appropriate if skill base and time not there
Secondary Services
• Expectation for the future (from Ministry of
Health):
– Insulin for type 2 diabetes patients will be initiated
by all GPs
• Mostly basal insulin + OHA, or pre-mixed insulin
bd
– May mean more patients are started on insulin early
(appropriately)
– Remember basal insulin only will not be sufficient for a
number of patients and long-term adjustment is required
• We are interested to see young type 2 pts < 25
yrs to provide intensive input
Summary
• Checklist for commencement of insulin
– Maximised lifestyle changes, OHA
– Patient willing; skill base in practice
• Decision on insulin regime depends on
–
–
–
–
BG profile ideally
HbA1c
Patient preference
Familiarity of your team with regimen and follow-up
required