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Insulin Initiation for Type 2 diabetes in General Practice. Nicole McGrath 2013. 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
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Insulin Initiation for Type 2 diabetes in General Practice Nicole McGrath 2013
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.
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 diabetesThe 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 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: 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)
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