Ministry of Health, Malaysia 2010

First published March 2011

Perkhidmatan Diabetes dan Endokrinologi
Kementerian Kesihatan Malaysia

Practical guide to

Insulin
Therapy

in Type 2
Diabetes Mellitus

Quick Reference For

Health Care Providers

X
SMBG and Insulin Titratuion

Pre Breakfast BG

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

2-hours Post-breakfast BG

Pre-breakfast rapid-acting or premixed insulin analogue.

Pre-lunch BG

Pre-breakfast short-acting or premixed insulin.

2 hours Post-lunch BG

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

Pre-dinner BG

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

Post-dinner/Pre-bed BG

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

KEY MESSAGES

1. Pancreatic beta cell dysfunction begins many years prior to

diagnosis of Type 2 diabetes

Pre-mixed Analogues TDS

2. Following diagnosis, progressive insulin deficiency combined with

insulin resistance results in worsening glycaemic control and failure

of oral anti-diabetic therapy.

3. Insulin therapy should be initiated early when HbA1c is persistently

above 8% despite optimal doses of oral anti-diabetic therapy.

X
X
X

4. The insulin regimen and insulin doses initiated should be

individualised, based on the patients blood glucose profile,

lifestyle factors and patients preferences.

X
X

X
Pre-mixed Analogues BD

5. Metformin, an insulin sensitizer, should be continued at optimal

doses following initiation of insulin therapy unless contraindications

or intolerance exist.
6. Self monitoring of blood glucose along with simple patient-directed

dose adjustments enable gradual, safe and prompt insulin dose

optimization.
7. Glycaemic targets need to be individualised based on patients

risk of hypoglycaemia, presence of complications and

co-morbidities.
8. Insulin regimens may need to be changed or intensified with time if

glycaemic targets are unmet despite dose optimization.

SMBG in Premixed Regimen

X
X

Pre-mixed Human BD

Adjust
To Control

X
X
X
X

X
X
Basal bolus (rapid-acting)

X
X
X

Bedtime
Pre
Dinner
Pre
Post
Lunch
Post
Pre
Breakfast
Pre
Post
SMBG in basal/basal-bolus regimen

X
Basal bolus (short-acting)
Basal only

9. Minimizing both hypoglycemia and weight gain are important

additional treatment targets for patients with Type 2 diabetes

requiring insulin therapy.
10. Continuous patient education and support is a key element for

optimal treatment adherence, patient empowerment and successful

insulin therapy.

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

TARGETS AND MONITORING

Recommended timing of SMBG in different Insulin Regimens

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

Onset

Peak (Hr)

Duration (Hr)

Timing of insulin

30 min
30 min

1-3
2-4

8
6-8

30 mins
before meal

10-20 min
0-15 min
5-15 min

1-3
1
1-2

3-5
3.5-4.5
3-5

5-15 mins before or

immediately
after meals

c) Intermediate-acting, NPH
- Insulatard*
- Humulin N*

1.5 Hr
1 Hr

4-12
4-10

18-23
16-18

Pre-breakfast / Pre-bed

d) Long-acting analogue
- Glargine*
- Detemir*

2-4 Hr
1 Hr

peakless
peakless

20-24
17-23

Same time everyday at

anytime of the day

e) Premixed human (30% regular insulin+70% NPH)

- Mixtard 30*
- Humulin 30/70*

30 min
30 min

dual
dual

18-23
16-18

30-60 mins
before meals

10-20 min
0-15 min

dual
dual

18-23
16-18

5-15 mins
before meals

a) Short-acting, regular
- Actrapid*
- Humulin R*
b) Rapid-acting analogue
- Novorapid (Aspart)*
- Humalog (Lispro)*
- Apidra (Glulisine)

f) Premixed analogue
- NovoMix 30
- Humalog Mix 25
* Available at Ministry of Health, Malaysia.

Insulin regimens and frequency of injections per day

No. of injections
per day

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

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

pre-breakfast, pre-lunch and pre-dinner

Insulin therapy 3 stage process

INITIATION

OPTIMISATION

INTENSIFICATION

Starting insulin

Dose titration to ensure maximum

benefit from prescribed treatment

Modification of an insulin regimen

to acieve glycemic control

Dose should be adjusted

every 3-7 days

Requires switching to more intensive

regimens for better glycemic control

Strat requires selection of appropriate

insulin regimen, insulin type and
starting dose.

Intensification of Premixed Regimen to Premix Plus

PREMIXED OD (pre-dinner) or BD
PREMIXED ONCE DAILY (pre-dinner)

PREMIXED TWICE DAILY (pre-breakfast, pre-dinner)

FPG 4-6 mmol/L, pre-lunch and pre-dinner > 6mmol/L

Add PRANDIAL INSULIN
(at morning and midday meal)

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

FPG and / or pre-dinner > 6 mmol/L

HbA1c > 6.5 8%

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
High Fasting / prebreakfast BG
Normal daytime BG

Start
BASAL only
(bedtime)
Optimise dose

Sequential addition of
prandial insulin
BASAL PLUS
(premeal and bedtime)

Optimise dose

Add 3 prandial
insulin

Start PRANDIAL
only (usually TDS
premeals)
Optimise dose
Add basal insulin

INTENSIFY

INITIATE &
OPTIMISE

Normal Fasting / prebreakfast BG

High 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

PREMIXED BD PLUS
PRANDIAL (prelunch)
Optimise dose

BASAL BOLUS (prandial insulin at premeals, basal insulin at bedtime)

Optimise dose

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

* refers to insulin analogues only

Insulin Initiation and Optimisation

Insulin Regimen

Starting Dose

Dose Optimisation

Optimal Dose

Basal

10 units or 0.2U/kg at bedtime

(0.1 units / kg if higher risk for
hypos)

Adjust insulin doses after 3 consecutive BG values

obtained (every 3 7 days)
Refer to (*)

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

Premixed

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)

Adjust insulin doses after 3 consecutive BG values

obtained (every 3 7 days)
Refer to (*)

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)

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 (*)

Prandial

Pre-breakfast BG determine pre-dinner premixed dose adjustment

Pre-dinner BG determine pre-breakfast premixed dose adjustment

Adjust the dose of prandial insulin of the preceding meal

(eg: if pre lunch BG is high, adjust pre-breakfast prandial insulin)

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.

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

(*) - < 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

Intensification from
Basal to Basal Plus 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

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

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

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

(*) - < 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