© 2013 Eli Lilly and Company The Optimisation and Intensification of Insulin Therapy in Type 2 Diabetes Speaker name and affiliation Prescribing information.

© 2013 Eli Lilly and Company

The Optimisation and Intensification of Insulin Therapy in Type 2 Diabetes

Speaker name and affiliation

Prescribing information is available on the last slide.UKDBT01539 September 2013

Intensification of insulin therapy

When current regimen is failing to achieve goals of therapy

Company Confidential © 2012 Eli Lilly and Company© 2013 Eli Lilly and Company

Agenda and learning points

3

The reality of intensification

Regimen change – the evidence

Basal plus and basal bolus – the practicalities of adding mealtime

insulin

BD mixtures

Next steps


What does intensification mean?

4

Type 2 diabetes is characterised by the progressive loss of beta cell function in addition to certain levels of insulin resistance.

Most people with Type 2 diabetes will need larger doses of insulin as compared to those with Type 1 diabetes, so understanding how to optimise the dose and intensify insulin therapy is vital if good glycaemic control is to be achieved.


Intensification with insulin

5

It becomes necessary when HbA1c goals / targets are not met despite optimum pharmacological interventions and lifestyle measures

When compliance is not an issue.

Note Managing sub-optimal diabetes control is not all about changing

treatment The most important aspect is identifying the reason for poor control

first, assessment should be thorough as:

Changing treatment alone may not improve control


The patient’s perspective

6

Insulin intensification usually means an increase in:

Number of injections

Frequency of blood glucose monitoring

Risk of hypoglycaemia particularly when blood glucose levels are getting closer to normal

Weight, majority of patients gain weight as glycaemic control improves

Pay more attention to meeting dietary and lifestyle requirements


Insulin therapy in diabetes

7

From the patient perspective, key messages are:

Ensure the patient is aware there are many options for insulin intensification

Self blood glucose monitoring is recommended in line with dose titration and ‘hypo’ awareness

Patient must understand dose ‘titration’ – i.e. change in dose to match changes in daily glucose, meals, activity….

Patient needs to understand the practicality of ‘hypos’ – i.e. prevention, recognition and treatment

Weight gain is a potential side effect – but can be managed Understanding key management e.g sick day care , driving restrictions


Typical initial insulin regimens

8

Intermediate acting insulin often given nocte – Humulin® I (isophane human insulin (prb))

– Insulatard® (isophane insulin)

– Insuman® Basal (isophane insulin)

Long acting analogue insulin– Lantus® (insulin glargine)

– Levemir® (insulin detemir)

– Tresiba® (insulin degludec)

BD MixturesAnalogue : – Humalog™ Mix25™ (25% insulin lispro (rDNA) injection. 75%insulin lispro protamine suspension)

– Humalog™ Mix50™ (50% insulin lispro (rDNA) injection. 50%insulin lispro protamine suspension)

– NovoMix30® (biphasic insulin aspart)

Human:– Humulin® M3 (human insulin(prb) 30%soluble insulin 70%isophane insulin)

– Insuman® Comb 25 (biphasic isophane insulin)

Insultard®, Levermir® and Tresiba® and NovoMix 30® are registered trademarks of Novo Nordisk LtdInsuman® Lantus® and Insuman® Comb 25 are registered trademarks of Sanofi Aventis


Intensifying insulin regimens:Options to consider

9

Quick reference guide to NICE Guidelines:

(CG87: May 2009)

Monitor those using basal insulin regimens (NPH or a long-acting analogue [insulin detemir, insulin glargine]) for need for short-acting insulin before meals or pre-mixed insulin

Monitor those using pre-mixed insulin once or twice daily for need for further injection of short-acting insulin before meals or change to mealtime plus basal regimen

NICE Type 2 diabetes CG87. London: NICE; May 2009; n/a: 1-431


Treating-To-Target in Type 2 Diabetes (4-T Study)

10

Three-year UK/Ireland study in 708 people with type 2 diabetes

First Phase – Year 1

One-year head-to-head comparison of efficacy of three different analogue insulins, when used as add-on therapy with dual oral antidiabetic therapy

Second Phase – Years 2 & 3

Evaluation over 2 more years of the need for more-complex insulin regimens, and the overall efficacy of three different randomized insulin treatment strategies


4-T study: 3 year efficacy of complex insulin regimens in Type 2 diabetes

11

Holman RR et al N Engl J Med 2009 361:1736-1747

TypeHbA1c (1year)

% 6.5 or under

Weight gain (kg) Hypoglycaemia

Biphasic 7.1% 31.9 % 5.7 kg 3.0

Pre-prandial 6.8% 44.8% 6.4 kg 5.7

Basal 6.9% 43.2% 3.6 kg 1.7

*Grade 2 or 3, median rates per patient per year


4-T study: 3 year efficacy of complex insulin regimens in Type 2 diabetes

12

Demographics No difference between 3 groups

– Age , Duration of diabetes, BMI, – HbA1c, Concomitant OHA’s

Results No statistically difference in median HbA1c between groups

– Differences in proportions reaching target level Hypos lowest in basal group Weight gain highest in prandial group

> 65% of patients who required intensification using a second insulin:– 67.7% for biphasic – 73.6% for prandial– 81.6% for basal

Holman RR et al N Engl J Med 2009 361:1736-1747


Intensifying insulin regimens

13

Which regimen?

There is no one ‘right’ choice, and one regimen is not necessarily forever. If it is unsuitable it should be changed

Who decides?

Your role is to explain the options and present all the pros and cons. The final decision must be made by the person themselves

Royal College of Nursing. Starting insulin treatment in adults with Type 2 diabetes 2006; NA: 1-28


Intensifying insulin therapy from basal

14

How do HCPs determine/define insulin “failure” ?

HbA1c unacceptable despite good fasting glucose control

Persistent hyperglycaemia during the day

Problematic day or night-time hypoglycaemia

Probable change required if large individual injection dose (e.g. >80 units) is

escalating and still not approaching FPG target

Increasingly patients with type 2 diabetes are being commenced on basal insulin


Common options for intensifying basal insulin regimens

15

Basal insulin

Switch to twice-daily premixed

insulin

Add once-daily prandial insulin with the largest

meal (basal-plus)

Add three times daily prandial

insulin with meals (basal-bolus)

Intensify with an additional

injection

Additional prandial

injections can be added

Adapted from Barnett A et al (2008) Int J Clin Pract 62: 1647–53


Insulin regimens for type 2 diabetes compared

16

• Frequent blood glucose monitoring


What next if not achieving goals of therapy on basal insulin alone?

17

Basal +*

Basal + +

Basal + + +

Insidious transfer to basal bolus or Basal + + +

Initiation as above is within HCP skill range

*Basal + indicates an insulin regimen of basal insulin, plus 1 bolus injection


What does basal bolus mean for the patient with Type 2 diabetes

18

4 – 5 injections per day

Choice of short/rapid acting insulin

Choice of long acting insulin

Choice of pen devices

Flexibility to adjust timing and dose of insulin

Increased frequency of blood glucose monitoring

Consider how many Type 2 patients either want to do this or could develop the skills to

manage a complex regime

Matching insulin activity profiles to diet

Options and Outcomes


Insulin activity profile of Basal +++

20

6 7 8 9 10 11 12 1 2 3 4 5 6 7 8 9 10 11 1 1 2 3

Long Acting insulin

Insu

lin

acti

vit

y

Aim of Long acting insulin is to manage glucose levels between mealsAim of Rapid acting insulin is to manage the glucose from the meals.

Rapid-Acting insulin

These diagrams are theoretical representations based on known pharmacological profiles, e.g. see Heise T et al (1998) Diabetes Care 21: 800-803


Carbohydrate awareness and Basal +++ in Type 2

21


Insu

lin a

ctiv

ity

Long Acting insulin


6 7 8 9 10 11 12 1 2 3 4 5 6 7 8 9 10 11 12 1 2 3

Time• Check BG levels 2 hours after meal• Eat similar amounts of carbohydrate at each meal• Inject same amount of rapid acting insulin at meals

Aim of Long acting insulin is to manage glucose levels between meals

Aim of Rapid acting insulin is to manage the glucose from the meals.


Challenges of Basal+++ in Type 2 diabetes

22

Because of insulin resistance, insulin sensitivity is poor

Self management of basal bolus / Basal+++

– Carbohydrate counting or awareness

– Correction doses are rarely taught to patients with Type 2 diabetes

Increasing insulin doses due to insulin resistance

Weight gain

Self titration/adjustment poor in many patients

Question

What makes Basal+++ successful in Type 2 diabetes?


Varying dose of rapid-acting insulin in Basal +++

23


Insu

lin

acti

vit

y

Long Acting insulin


6 7 8 9 10 11 12 1 2 3 4 5 6 7 8 9 10 11 12 1 2 3

Time


Adding pre-meal insulin to basal

24

Patients who fail to reach treatment goals despite maximum oral therapy and basal insulin could require the addition of pre-meal short or rapid acting insulin in order to improve postprandial control.

Start with the addition of one injection of pre-meal insulin with the biggest meal, largest carbohydrate intake

Titrate on a meal by meal basis to achieve postprandial blood glucose goal Initially 10% of the patient’s basal insulin dose should be replaced by the pre -meal

insulin

These are general guidelines and management should be individualised for specific patients.

Hirsch IB et al Clinical Diabetes 2005 23;2:78-86


Factors to consider before implementing a basal plus approach

25

Is the patient willing and able to take 4 – 5 injections a day?

Will the patient be able to develop an understanding of carbohydrate content of meals?

Will the patient be able to adjust their insulin dose based on the above?

If not...........

Hirsch IB et al Clinical Diabetes 2005 23;2:78-86


What next if not achieving goals of therapy on basal insulin alone?

26

Is a BD mixture more appropriate?


Transferring patients from a once-daily basal insulin to a BD mixture

27

Assess patients suitability for fixed mixtureDo they eat regular meals ?Do they miss meals ever ? Is the timing of meals similar each dayUse structured blood glucose monitoring and diet assessment (discovery sheets) to determine above and how current basal insulin dose should be split when initiated


Discovery sheets

28

Used for up to 7 days to facilitate a structured blood glucose monitoring approach

Patients are asked to record pre and post prandial blood glucose results, alongside food eaten

Helps determine pre prandial blood glucose control & post prandial response to carbohydrate intake

Engages and facilitates patients making the connection between blood glucose monitoring results and food eaten

Engages patients in identifying possible solutions.

Facilitates HCP with the patient to decide next best insulin solution.


Discovery sheets

29


Transferring patients from a once-daily basal insulin to a BD mixture

30

Caution should be taken when transferring from one insulin to another

When transferring to either a 30/70 or 25/75 premixed insulin– The total daily dose of basal insulin can be split by different ratios

– 50% of the total basal dose given pre breakfast

– 50% of the total basal dose given pre evening meal

– Or – 70% of the total basal dose pre breakfast

– 30% of the total basal dose pre evening meal

Initial targets for fasting and pre-evening meal glucose levels (5-7 mmol/l)

Use fasting glucose to titrate evening dose and pre-evening meal to titrate am dose

Use patients bgm diary and food diary (or discovery sheet) to determine how best to spilt insulin dose

Hirsch IB et al Clinical Diabetes 2005 23;2:78-86AccessMedicine Harrison's Online. Chapter 344: Diabetes Mellitus 2011; N/A: 1-12


Practicalities of changing from basal insulin to pre mixed insulin

31

Having decided on how the pre mixed insulin is to be split between pre breakfast and evening meal – (eg 50% am /50% pm or 70% am /30% pm)

Day 1– First dose of pre mixed insulin is given with evening meal– Basal insulin stopped

Day 2– First dose of morning pre mixed insulin is given– Followed by second dose of pre mixed insulin with evening meal


Challenges of BD mixtures in Type 2

32

Perceptions, seen as: More complex to initiate and titrate than a basal insulin Depending on individual lifestyle, may be seen as

inflexible compared with Basal+++ Planned snacking required for some patients May cause more weight gain and more hypoglycaemia

than basal regimens Basal bolus seen by some as the gold standard insulin

therapy

Raskin P et al. Diabetes Care, 2005 28: 260-265


Advantages of premixed insulin analogues

33

Rapid acting insulin analogues exhibit earlier and higher peak

metabolic activity and shorter duration of action than human insulin

Both basal and rapid-acting prandial insulin are provided in every

injection and are effective and simple for patients to use

Can be injected up to 3x daily and can effectively control postprandial

hyperglycaemia

Potentially improve postprandial glycaemic excursions throughout a

24hr period

Rosenstock J, et al. Diabetes Care 2008; 31:20-25


Activity profile of premixed insulin analogues

34

These diagrams are theoretical representations based on known pharmacological profiles, e.g. see HeiseT et al (1998) Diabetes Care 21: 800-803

Long Acting insulin


For a 75/25 premixed insulin analogue this is how units break down

Long-acting insulin component manages glucose levels between mealsRapid-acting insulin component manages glucose load from the meals.


Activity profile of premixed insulin analogues

35

These diagrams are theoretical representations based on known pharmacological profiles, e.g. see HeiseT et al (1998) Diabetes Care 21: 800-803

Long Acting insulin


Aim of Long acting insulin is to manage glucose levels between mealsAim of Rapid acting insulin is to manage the glucose from the meals.


Eating under the curve!

36

Patients taking mixtures need to be aware they need to eat similar amounts of carbohydrate. Post prandial blood glucose monitoring will help the patient determine carbohydrate portion size to match insulin profile


How do you determine/define BD premixed insulin “failure”

37

HbA1c unacceptable

Persistent hyperglycaemia (either pre-injection or post-prandial are high-risk times)

Problematic day or night-time hypoglycaemia (pre lunch and pre/post bed are high-

risk times)

Variable hypoglycaemia and hyperglycaemia because of lack of flexibility in twice-

daily regimen


What next if not achieving goals of therapy on BD mixture?

38

Options:

Add in prandial insulin lunchtime

Basal bolus

TDS Mix

Combination of different mixtures

The next intensification option will be determined by blood glucose profiles and patients

food diary


Intensifying insulin therapy

39

Summary

Changing insulin regimen alone may not improve control

Assess factors influencing poor control

Intensifying insulin therapy typically means increasing the number of injections per day

Consider the patients physical and cognitive ability to take on a more complex insulin regimen

Ensure patients are involved in their treatment – providing appropriate education so enabling them to make informed choices about the potential options when intensifying their insulin therapy

UKDBT01539 September 2013

© 2013 Eli Lilly and Company The Optimisation and Intensification of Insulin Therapy in Type 2 Diabetes Speaker name and affiliation Prescribing information.

Documents

eli lilly

companycompany confidential

larger doses of insulin

blood glucose levels

dose titration

poor control

good glycaemic control

daily glucose