Insulin Therapy

Practical guide to

in Type 2 Diabetes Mellitus

Ministry of Health, Malaysia 2010 First published March 2011 Perkhidmatan Diabetes dan Endokrinologi Kementerian Kesihatan Malaysia

Quick Reference For Health Care Providers

Bedtime Pre X

KEY MESSAGES
1. 2. Dinner Pre Post X Following diagnosis, progressive insulin deficiency combined with insulin resistance results in worsening glycaemic control and failure of oral anti-diabetic therapy. Insulin therapy should be initiated early when HbA1c is persistently above 8% despite optimal doses of oral anti-diabetic therapy. X The insulin regimen and insulin doses initiated should be individualised, based on the patients blood glucose profile, lifestyle factors and patients preferences. Metformin, an insulin sensitizer, should be continued at optimal doses following initiation of insulin therapy unless contraindications or intolerance exist. Self monitoring of blood glucose along with simple patient-directed dose adjustments enable gradual, safe and prompt insulin dose optimization. Glycaemic targets need to be individualised based on patients risk of hypoglycaemia, presence of complications and co-morbidities. Pancreatic beta cell dysfunction begins many years prior to diagnosis of Type 2 diabetes X

Pre-bed intermediate/long-acting insulin or pre-dinner premixed X X

Pre-lunch rapid-acting or pre-breakfast premixed insulin. X X X Lunch Post X Pre X X Recommended timing of SMBG in different Insulin Regimens Breakfast Pre Post X X X X X X X

Pre-lunch short-acting or pre-breakfast premixed insulin.

Pre-breakfast rapid-acting or premixed insulin analogue.

3. 4.

5.

6.

7.

9.

SMBG in Premixed Regimen

SMBG and Insulin Titratuion

To Control

2-hours Post-breakfast BG

Pre-mixed Analogues TDS

Basal bolus (short-acting)

Basal bolus (rapid-acting)

Pre-mixed Analogues BD

10. Continuous patient education and support is a key element for optimal treatment adherence, patient empowerment and successful insulin therapy.

SMBG in basal/basal-bolus regimen

Minimizing both hypoglycemia and weight gain are important additional treatment targets for patients with Type 2 diabetes requiring insulin therapy.

TARGETS AND MONITORING

8.

Insulin regimens may need to be changed or intensified with time if glycaemic targets are unmet despite dose optimization.

Basal only

The development of this quick reference guide was supported by an educational grant from sanofi-aventis

Pre-dinner BG

Pre-lunch BG

SOURCES OF FUNDING

Post-dinner/Pre-bed BG Pre-mixed Human BD Pre Breakfast BG

2 hours Post-lunch BG

Pre-dinner rapid-acting or pre-dinner premixed insulin. X X X X

Pre-breakfast short-acting or premixed insulin.

Adjust

Intensification from Premixed Regimen to Basal Bolus Regimen PREMIXED INSULIN BD or TDS (Insulin analogue) FPG / premeals > 6 mmol/L HbA1c > 6.5 7% Switch to BASAL BOLUS REGIMEN Starting dose 0.5units/kg/day or total dose transfer Split dose 50:50 for basal and prandial insulin Divide prandial doses into 3 main meals Fix FPG < 6mmol/L using basal insulin Titrate bolus dose once / twice a week to achieve FPG and preprandial goal < 6mmol/L Stop SU, continue metformin Intensification from Prandial Regimen to Basal Bolus Regimen PRANDIAL TDS (Optimised prandial doses) FPG > 6 mmol/L HbA1c > 6.5 8% Addition of BASAL INSULIN BASAL BOLUS REGIMEN 10 units or 0.2U / kg at pre-dinner Monitor FPG , target 4-6 mmol/L Adjust basal insulin doses after 3 consecutive BG values obtained (every 3 7 days) - < 4 mmol/L ( > 1 value ) reduce dose by 2 units - 4-6 mmol/L ( all values ) maintain current dose - > 6 mmol/L ( >1 value, no hypos ) increase by 2 units

INSUlIN PREPARATIONS AvAIlAblE IN MAlAYSIA AND THEIR PHARMACOKINETIC PROFIlES

Brand (Generic) Name
a) Short-acting, regular - Actrapid* - Humulin R* b) Rapid-acting analogue - Novorapid (Aspart)* - Humalog (Lispro)* - Apidra (Glulisine) c) Intermediate-acting, NPH - Insulatard* - Humulin N* d) Long-acting analogue - Glargine* - Detemir* e) Premixed human (30% regular insulin+70% NPH) - Mixtard 30* - Humulin 30/70* f) Premixed analogue - NovoMix 30 - Humalog Mix 25
* Available at Ministry of Health, Malaysia.

Onset
30 min 30 min 10-20 min 0-15 min 5-15 min 1.5 Hr 1 Hr 2-4 Hr 1 Hr 30 min 30 min 10-20 min 0-15 min

Peak (Hr)
1-3 2-4 1-3 1 1-2 4-12 4-10 peakless peakless dual dual dual dual

Duration (Hr)
8 6-8 3-5 3.5-4.5 3-5 18-23 16-18 20-24 17-23 18-23 16-18 18-23 16-18

Timing of insulin
30 mins before meal 5-15 mins before or immediately after meals

Pre-breakfast / Pre-bed

Same time everyday at anytime of the day 30-60 mins before meals 5-15 mins before meals

INSUlIN REGIMENS AND FREQUENCY OF INjECTIONS PER DAY

No. of injections per day
1

Insulin regimen
BASAL BASAL PREMIXED OD BASAL PREMIXED BD BASAL-PLUS (1) BASAL-PLUS (2) PRANDIAL PREMIXED TDS PREMIXED-PLUS PREMIXED-PLUS BASAL-BOLUS BASAL-BOLUS

Type of insulin and timing

Intermediate acting (NPH) insulin pre-bed Long-acting analogue once daily Premixed/ premixed analogue pre-dinner Intermediate acting (NPH) pre-breakfast and pre-dinner Premixed insulin pre-breakfast and pre-dinner Basal insulin once daily + 1 prandial insulin Basal insulin once daily + 2 prandial insulin Prandial insulin pre-breakfast, pre-lunch and pre-dinner Premixed analogue pre-breakfast, pre-lunch and pre-dinner Premixed insulin pre-breakfast, pre-dinner + 1 prandial insulin pre-lunch
Prandial insulin pre-breakfast and pre-lunch + premixed insulin pre-dinner Basal insulin once daily + prandial insulin pre-breakfast, pre-lunch and pre-dinner

4 5

Intermediate acting (NPH) insulin pre-breakfast and pre-dinner + prandial insulin pre-breakfast, pre-lunch and pre-dinner

INSUlIN THERAPY 3 STAGE PROCESS INITIATION

Starting insulin
Strat requires selection of appropriate insulin regimen, insulin type and starting dose.

OPTIMISATION
Dose titration to ensure maximum benefit from prescribed treatment
Dose should be adjusted every 3-7 days

INTENSIFICATION
Modification of an insulin regimen to acieve glycemic control
Requires switching to more intensive regimens for better glycemic control

Intensification of Premixed Regimen to Premix Plus

PREMIXED OD (pre-dinner) or BD
PREMIXED ONCE DAILY (pre-dinner) FPG 4-6 mmol/L, pre-lunch and pre-dinner > 6mmol/L Add PRANDIAL INSULIN (at morning and midday meal) PREMIXED TWICE DAILY (pre-breakfast, pre-dinner) Pre-dinner > 6 mmol/L Add PRANDIAL INSULIN (at midday meal)

Add prandial insulin 6 units or 0.1unit/kg Titrate to next prandial BG target daily If subsequent pre-meal BG is - < 4 mmol/L ( > 1 value ) reduce dose by 2 units - 4-6 mmol/L ( all values ) maintain current dose - > 6 mmol/L ( >1 value, no hypos ) increase by 2 units

Intensification from Premixed Regimen

PREMIXED OD PREMIXED BD
PREMIXED BD PLUS PRELUNCH PRANDIAL PREMIXED TDS (FOR ANALOGUES) BASAL BOLUS

Intensification of Premixed Regimen

PREMIXED OD (pre-dinner) or BD
FPG and / or pre-dinner 4-6 mmol/L HbA1c > 6.5 8% FPG and / or pre-dinner > 6 mmol/L Titrate Premix OD or BD to achieve FPG and / or predinner < 6mmol/L

SWITCH TO PREMIXED BD OR TDS (analogues only) DAILY (OD) TWICE DAILY (BD) Starting dose 0.3units/kg/day or total dose transfer Split the dose 50:50 pre-breakfast and pre-dinner Titrate insulin dose to achieve FPG and pre-dinner<6mmol/L TWICE DAILY (BD) THREE TIMES DAILY (TDS) Add 6 units or 10% total daily dose at lunch Titrate dose once or twice a week to next pre prandial goal < 6mmol/L Down titrate morning dose ( 2 4 units ) may be needed after adding lunch dose Continue metformin Consider premixed analogues if hypos

SUMMARY OF TREATMENT AlGORITHM

Newly diagnosed DM & Type 2 DM Symptomatic (osmotic symptoms) regardless HbA1c or FBS HbA1c > 10% or FPG > 13 mmol/L Type 2 DM on maximal OADs (single/double/triple) HbA1c > 8%

Glycemic abnormality? FPG, SMBG Normal Fasting / prebreakfast BG High daytime BG High Fasting / prebreakfast BG Normal daytime BG Start PREMIXED OD (predinner) Optimise dose PREMIXED TDS* (premeals) Optimise dose High Fasting / prebreakfast BG High daytime BG Start PREMIXED BD (prebreakfast & predinner) Optimise dose Start BASAL BOLUS (premeals, bedtime) Optimise dose

INITIATE & OPTIMISE

Start PRANDIAL only (usually TDS premeals) Optimise dose Add basal insulin Sequential addition of prandial insulin

Start BASAL only (bedtime) Optimise dose Add 3 prandial insulin

INTENSIFY

BASAL PLUS (premeal and bedtime)

Optimise dose

PREMIXED BD PLUS PRANDIAL (prelunch) Optimise dose

BASAL BOLUS (prandial insulin at premeals, basal insulin at bedtime) Optimise dose
* refers to insulin analogues only

Note: 1. Metformin should be continued while on insulin therapy unless contraindicated or intolerant 2. Sulphonylureas / Meglitinides should be withdrawn once prandial insulin is used regularly with meals 3. Insulin dose should be optimized prior to switching / intensifying regimens

INSUlIN INITIATION AND OPTIMISATION

Insulin Regimen Starting Dose
10 units or 0.2U/kg at bedtime (0.1 units / kg if higher risk for hypos) Once daily: 10 units or 0.2U/kg at pre-dinner Twice daily: 10 units or 0.2U/ kg at pre-breakfast and predinner (0.1units/kg if higher risk for hypos)

Dose Optimisation Adjust insulin doses after 3 consecutive BG values obtained (every 3 7 days) Refer to (*) Adjust insulin doses after 3 consecutive BG values obtained (every 3 7 days) Refer to (*)
Pre-breakfast BG determine pre-dinner premixed dose adjustment Pre-dinner BG determine pre-breakfast premixed dose adjustment

Optimal Dose 0.2 0.3 units/kg in lean patients 0.4 0.5 units/kg in most patients Up to 0.7 units/kg in obese patients Total daily dose of 0.5 1.0 units/kg in most patients (Maybe more than 1.0 units/kg/day in obese, insulin resistant patients)

Basal

Premixed

Prandial

6 units or 0.1units/kg for each meal with short-acting or rapid-acting analogue.

Adjust insulin doses after 3 consecutive BG values obtained (every 3 7 days) Refer to (*)
Adjust the dose of prandial insulin of the preceding meal (eg: if pre lunch BG is high, adjust pre-breakfast prandial insulin)

Prandial dose for each meal will vary according to carbohydrate content and amount. Dose should ideally not exceed 0.5U/kg/dose. Generally basal insulin would contribute 50% of total daily insulin dose and prandial insulin would contribute remaining 50% (distributed over three main meals).
Refer to Prandial Section & Basal Section

Basal Bolus

Prandial Insulin: 6 units or 0.1U/kg before each meal Basal insulin: 10 units or 0.2U/kg at bedtime

Refer to Prandial Section Refer to Basal Section Aim for normal pre-breakfast BG first by adjusting the dose of bed-time basal insulin before adjusting the prandial (bolus) insulin dose.

(*) - < 4 mmol/L (> 1 value) reduce dose by 2 units - 4-6 mmol/L (all values) maintain current dose - > 6 mmol/L (>1 value, no hypos) increase by 2 units

INSUlIN INTENSIFICATION
Intensification from Basal Regimen

BASAL
PREMIXED BD BASAL BOLUS BASAL PLUS (1 / 2 / 3 PRANDIAL)
Note: Optimise Basal Before Intensification Fix Fasting Blood Glucose (FBG) first using basal insulin (dose optimisation) Goal FBG 4 6 mmol/L Consider adding bolus / meal insulin when: Hb A1c > 7% and FBG at goal or basal insulin dose > 0.5U/kg

Intensification from Basal to Premixed Regime

Switch to PREMIXED TWICE DAILY Total dose transfer Split dose 50:50 pre-breakfast : pre-dinner Titrate dose once / twice a week to next preprandial goal Stop SU, continue metformin Consider premixed analogue

Intensification from Basal to Basal Bolus regimen

Add prandial insulin 6 units or 0.1unit/kg at each meal Monitor BG up to 4 times per day Titrate to next pre-meal / bedtime BG target daily If subsequent pre-meals BG are Refer to (*) Stop SU and continue metformin

Intensification from Basal to Basal Plus regimen

Add initial dose of prandial 6 units or 0.1unit/kg at largest meal Titrate to next pre-meal / bedtime BG target daily If subsequent premeals BG are Refer to (*) Discontinue SU on addition of prandial insulin Continue metformin Patients may need to perform SMBG up to 4 times per day If HbA1c > 6.5 - 7% after 3 months despite titrating doses, or prandial doses > 30U per meal, consider: Add 2nd dose of prandial insulin at 6 units or 0.1unit/kg at 2nd largest meal and titrate as before Subsequently may add 3rd dose of prandial insulin if required

If HbA1c > 6.5 - 7% after 3 months despite titrating prandial doses or prandial doses > 30 units per meal, consider: Resume optimisation of basal insulin up to 0.7 U/kg Perform 7- point BG profile

(*) - < 4 mmol/L (> 1 value) reduce dose by 2 units - 4-6 mmol/L (all values) maintain current dose - > 6 mmol/L (>1 value, no hypos) increase by 2 units