INSULIN INTENSIFICATION (SWITCHING INSULIN REGIMENS)

1 Switching from basal to basal plus regimen.

2 Switching from basal to basal bolus regimen.

3 Switching from basal to premixed regimen.

4 Switching from premixed to basal bolus regimen.

5 Switching from single to multiple premixed regimen.

6 Intensification of premixed regimen with addition of pre-meal bolus.

7 Intensification of prandial regimen with addition of basal insulin.

INSULIN INTENSIFICATION

T2DM is a progressive disease. With increasing duration of disease, there is increasing fasting and
postprandial hyperglycemia as a result of progressive pancreatic beta-cell failure. Therefore insulin
therapy needs to be a dynamic process, to address progressive insulin deficiency.

The use of a single insulin regimen may often not ensure durable glycemic control over time despite
optimisation of insulin doses. Many patients are left on an inadequate insulin regimen for too long
resulting in sub-optimal glycemic control. Intensifi cation enables modification of an insulin regimen,
either with additional injections or switching to different insulin types, towards achieving better
glycemic control.

Key elements for successful insulin intensification

Patient education

Dedicated diabetes team - diabetes educator, pharmacist, dietician

Self-blood glucose monitoring (SMBG)

Frequent contact with health care team

Support group

Insulin intensification can be done in many ways. The choice would depend on the pre-existing
insulin regimen, the abnormal glycemic pattern, patient acceptance and lifestyle issues.

Basal insulin regimens can be intensified by any of the following ways

Switching to premixed regimen (usually twice daily)

Addition of three pre-meal rapid / short-acting insulin – basal-bolus regimen

Sequential addition of pre-meal rapid / short-acting insulin – basal-plus regimen.

Premixed insulin regimens can be intensifi ed by any of the following ways

Additional injections of premixed insulin (twice and three times daily)

Addition of pre-meal rapid / short-acting at lunch

Switching from Basal to Basal plus regimen

For those patients on combination OADs and basal insulin not achieving HbA1c targets despite
optimal fasting BG, addition of prandial insulin to address postprandial hyperglycemia will help
improve overall glycemic control. This can be initiated with addition of single prandial insulin prior to
the largest meal of the day or to address the highest postprandial BG of the day1,2. With time,
additional prandial insulin can be added prior to other meals to address postprandial hyperglycemia.
Intensification of the Basal – Plus regimen (sequential addition of prandial insulin) will ultimately
lead to Basal – Bolus regime.

Intensification from Basal to Basal – Plus regimen

Switching from Basal to Basal bolus regimen

For those patients on combination OADs and basal insulin not achieving HbA1c targets despite
optimal fasting BG, with post-prandial hyperglycemia identified following all main meals, addition of
prandial insulin prior to each meal will help improve overall glycemic control. Sulphonylureas should
be stopped but Metformin should be continued.
Intensification from Basal to Basal – Bolus regimen

Switching from Basal to Premixed regimen

For those patients on combination OADs and basal insulin not achieving HbA1c targets despite
optimal fasting BG, with post-prandial hyperglycemia, another option for intensification would be to
switch to a premixed regimen. This option is usually appropriate for patients who prefer a simpler
regimen and are unable to accept 3 – 4 injections per day. This regimen is more suitable for those
with a rigid lifestyle. Sulphonylureas should be stopped but Metformin should be continued. Dose
for dose transfer can be used where the total daily dose of basal insulin is used to determine
premixed total daily dose. Premixed is then administered in two divided doses, usually equal in
amount ie: split dose 50: 50 at pre-breakfast and pre-dinner.

Intensification from basal to premixed regimen

Premixed analogues may be considered in patients experiencing hypoglycaemia with conventional
premixed insulin and in those who desire greater flexibility as administration of premixed analogue
does not require specific timing prior to meals and may be injected just prior to, during, or
immediately after, a meal.

Switching from Premixed to Basal bolus regimen

For those patients on premixed regimen (twice or three times daily) and not achieving HbA1c targets
despite optimised dose, another option for intensification would be to switch to basal-bolus
regimen. This option is appropriate for patients who require greater flexibility in dose adjustment as
it potentially allows pre-meal rapid / short-acting insulin to be adjusted individually according to
blood glucose level (correctional bolus) as well as the carbohydrate meal content of the meal.

Intensification from premixed regimen to basal bolus regimen

The initial total daily dose following the switch may be guided by using a simple dose calculation of
0.5units/kg or by a total dose for dose transfer from the prior total daily dose on the previous
regimen. Following determination of total daily dose requirement, proportion of basal to prandial
insulin requirement may be estimated using a ratio of 50:50. A smaller proportion of basal insulin
may also be used such as between 25 – 40% of total daily dose in certain circumstances. The basal
dose is usually administered at bedtime (conventional insulin) and the prandial portion is divided
into three to cover the three main meals, administered pre-meals. Estimation of the pre-meal dose
should take into consideration the size of the meal, in terms of the carbohydrate content.
Subsequently the basal and pre-meal insulin should be titrated or optimised accordingly towards
attaining glycemic targets.

Switching from single to multiple premixed regimen

For those patients already on a single premixed insulin regimen, usually in combination with single
or multiple OADs and not achieving blood glucose and HbA1c targets despite optimising insulin and
OAD doses, an option for intensification would be to initiate additional pre-meal doses of premixed
insulin. For those on single dose conventional premixed insulin, usually prior to evening meals, one
additional dose may be initiated prior to the morning meal. In those receiving premixed analogue
insulin, additional doses may be initiated at both morning and midday meals, either sequentially or
simultaneously. It is not usual to administer conventional premixed insulin more than twice daily in
view of concern for between-meal hypoglycaemia.
Intensification of premixed regimen

Intensification of premixed regimen with addition of pre-meal bolus

For those patients already on a premixed daily regimen usually in combination with single or
multiple OADs and not achieving blood glucose and HbA1c targets despite optimising insulin and
OAD doses, an option for intensification would be to initiate additional injections of pre-meal rapid
or short-acting insulin. Whereas for those patients already on premixed twice daily regimen and not
achieving blood glucose and HbA1c targets despite optimising insulin doses, an option for
intensification would be to initiate pre-lunch rapid or short-acting insulin.

Intensification of premixed regimen with addition of prandial insulin

Intensification of prandial regimen with addition of basal insulin

For those patients already on prandial only regimen usually with each meal and not achieving HbA1c
and blood glucose targets (particularly fasting BG despite optimising doses of prandial insulin), an
option for intensification would be to initiate basal insulin, usually at bedtime. Basal insulin analogue
may be added in the daytime as an alternative to bedtime dosing. Therefore the prandial regimen is
intensified to a basal bolus regimen.

Intensification of prandial regimen with addition of basal insulin

REFERENCES

1. Insulin intensification strategies in type 2 diabetes: when one injection is no longer sufficient A. J.
Garber Diabetes, Obesity and Metabolism Special Issue: Perspectives in Type 2 Diabetes:
Incorporating the Latest Insulin Analogue Strategies to Achieve Treatment Success Volume 11, Issue
Supplement s5, pages 14–18, November 2009.

2. Options for the intensification of insulin therapy when basal insulin is not enough in type 2
diabetes mellitus D. Raccah Diabetes, Obesity and Metabolism Special Issue: Insulin Glargine:
Cornerstone Treatment for Type 2 Diabetes Patients Volume 10, Issue Supplement s2, pages 76–82,
July 2008 (basalplus).

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twice-, or thrice-daily dosing with biphasic insulin aspart 70/30 (The 1-2-3 study). Diabetes Obes
Metab 2006; 8: 58-66.

4. Bebakar WM, Chow CC, Kadir KA et al. Adding biphasic insulin aspart 30 once or twice daily is
more efficacious than optimizing oral antidiabetic treatment in patients with type 2 diabetes.
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Intensification with prandial insulin. Pfützner A, Forst T .Int J Clin Pract Suppl. 2009 Oct;(164):11-4.