Does the patient need insulin?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)

Diagnosis of type 2 diabetesß-cell function and insulin secretion progressively decline in

type 2 diabetes

Type 2 diabetes is a progressive disease that requires Type 2 diabetes is a progressive disease that requires progressive treatmentprogressive treatment

Is insulin going to be effective?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 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 insulinOnce 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 Basal Insulin: provides background insulin but does not cover mealsinsulin but does not cover meals

•Schematic action profiles, theoretical representation of insulin injected once a day - results may vary from patient to patient.

Isophane Glargine

Once daily Isophane insulin (Protophane or Once daily Isophane insulin (Protophane or Humulin NPH): IndicationsHumulin 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 DoseIsophane 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) insulinGlargine (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) InsulinGlargine (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): IndicationsOnce 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 diabetesThe problem with type 2 diabetesThe mealtime insulin secretory response is blunted…The mealtime insulin secretory response is blunted…

...resulting in undesired mealtime glucose excursions

Both fasting & mealtime glucose contribute to HbABoth fasting & mealtime glucose contribute to HbA1c1c

• 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 Oral hpoglycaemic agents (OHA) and basal insulin(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 Suphonylureas and basal insulininsulin

• 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 Some typical treatment regimens: OHA and basal insulininsulin

• 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 OHAOther 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?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 CoverInsulin 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 insulinOnset 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 insulinShort 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 InsulinsRapid 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 regimesBasal 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 regimensBasal 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 InsulinsPre-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 short-acting 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: Pre-mixed Insulins: Short acting insulin + isophaneShort 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: Pre-mixed Insulins: Rapid acting insulin + isophaneRapid 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 prescriptionInsulin 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 dosesAdjusting 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

Blood testing times

Before breakfast Reducecloudy night time insulin by 2

units

Good Control

Increasecloudy night time insulin

by 2 units

Increasecloudy night time insulin

by 4 units.

Before lunch Reduce breakfast insulin by 2 units

Good Control

Increasebreakfast insulin by 2

units

Increasebreakfast insulin by 4

units

Before evening meal Reducelunch insulin by 2 units

Good Control

Increase Lunch insulin by 2 units

Increaselunch insulin by 4 units

Before bed Reduceevening insulin by 2 units

Good Control

Increaseevening insulin by 2

units

Increaseevening insulin by 4

units

Increasing Insulin Doses: Increasing Insulin Doses: Isophane nocteIsophane 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 (= Twice daily Isophane (= Glargine)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 testingPost-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)!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 suboptimalHbA1c 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 RegimensChanging 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 When to refer to Secondary servicesservices

• 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 ServicesSecondary 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

SummarySummary

• 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