Case study 2:

Insulin regimens for

intensification in T2DM
Agenda

Insulin Barriers Guidelines

Intensification: to insulin on insulin Case based
Rationale & intensification intensification discussion
Definition
Major guidelines target an HbA1c of <7.0 %

Overall aim is to achieve glucose levels as close to normal as possible

This can minimise development and progression of microvascular and
macrovascular complications

FPG PPG
ADA/ HbA1c
<130 mg/dL <180 mg/dL
<7.0 %
EASD (7.2 mmol/L) (10.0 mmol/L)

FPG PPG
HbA1c
IDF <110 mg/dL
<7.0 %
<160 mg/dL
(6.0 mmol/L) (9.0 mmol/L)

FPG, fasting plasma glucose; PPG, postprandial plasma glucose; ADA, American Diabetes Association;
EASD, European Association for the Study of Diabetes; IDF, International Diabetes Federation

1. ADA. Diabetes Care 2018;41:S13–27; 2. Inzucchi et al. Diabetologia 2012;55:1577–96; 3.

3. IDF Clinical Guidelines Task Force. Global guidelines for type 2 diabetes. 2017
Impact of Intensive Therapy For Diabetes:
Summary of Major Clinical Trials

Study Microvasc. CVD Mortality

UKPDS      

DCCT / EDIC*       Initial trial

Long-term
ACCORD    follow-up

ADVANCE   

VADT   

Kendall DM, Bergenstal RM. ©International Diabetes Center 2009. UK Prospective Diabetes Study Group. Lancet 1998; 352:854;
Holman et al. N Engl J Med 2008;359:1577; DCCT Research Group. N Engl J Med 1993;329;977; Nathan et al. N Engl J Med 2005;353:2643;
Gerstein et al. N Engl J Med 2008;358:2545; Patel et al. N Engl J Med 2008;358:2560;
Duckworth et al. N Engl J Med 2009;360:129 (erratum); Moritz. N Engl J Med 2009;361:1024
Defining Insulin Intensification

Starting insulin therapy

INITIATE

Dose titration to ensure that patients receives

maximum benefit from the prescribed treatment
OPTIMISE

Modification of insulin regimen

(adding to or changing the therapy in order to
INTENSIFY maintain glycaemic control)
Multiple options to achieve targets

Oral-only
Non-insulin Regimens

Injectable GLP-1 RA

Basal Insulin
Insulin Regimens

Premixed/co-formulation

Basal–bolus
Agenda

Insulin Barriers Guidelines

Intensification: to insulin on insulin Case based
Rationale & intensification intensification discussion
Definition
Only 19% of diabetes patients in India are
in good glycaemic control!!

Mean HbA1c (8.9 ± 2.8%)

that is almost 2% higher than
ADA recommended target
19%
Poor glycemic control despite
being on treatment
 93.2% of the patients were on OADs
 35.2% were on insulin

OADs = Oral anti-diabetic drugs

Mohan, et al.: Results from the DiabCare India 2011 Study
Insulin optimization and intensification
should follow disease progression

Lifestyle + OADs
function (%)

Basal insulin + OADs

Beta cell

Titrate dose to reach/maintain glycaemic targets

Initiate Basal and 1-4 bolus Or Premix

Intensify for mealtime insulin coverage

Optimise

Intensify

Treatment optimization and intensification

Schematic diagram adapted from Kahn. Diabetologia 2003; 46:3–19
Inzucchi et al. Diabetologia 2012;55(6):1577-96.
Why intensification is delayed ?

Treatment
complexity
Inflexible
regimens
Hypoglycaemia

Weight gain
Clinical inertia

UKPDS 34. Lancet 1998:352:854–65

Agenda

Insulin Barriers Guidelines

Intensification: to insulin on insulin Case based
Rationale & intensification intensification discussion
Definition
ADA 2017
Usually with metformin +/- other noninsulin agent
Start: 10U/day or 0.1-0.2 U/Kg/day
Adjust: 10-15% or 2-4 units once or twice weekly to reach FBG target
For Hypo: Determine & address cause; if no clear reason for hypo,  dose by 4 units or 10-20%
Add 1 rapid-acting insulin injection before largest meal
Start: 4 units, 0.1U/Kg/day or 10% basal dose. If A1c
<8%,consider  basal by same amount
Adjust:  dose by 1-2 units or 10-15% once or twice
weekly until SMBG target reached
For Hypo: Determine & address cause; if no clear reason
for hypo,  dose by 2-4 units or 10-20%
If A1c is not controlled,
advance to basal bolus
Add ≥ 2 rapid-acting insulin injection before meals
(‘basal-bolus’)
Start: 4 units, 0.1 U/Kg/day or 10% basal dose. If A1c
<8%, consider  basal by same amount
Adjust:  dose(s) by 1-2 units or 10-15% once or twice
weekly to achieve SMBG target.
For Hypo: Determine & address cause; if no clear reason
for hypo,  dose by 2-4 units or 10-20%
Diabetes Care Volume 40, Supplement 1, January 2017
Initiate basal Insulin
If A1c not controlled, consider
combination injectable therapy
Add GLP-1 RA
If not tolerated or A1C target not reached,
change to 2 insulin injection regimen
If goals are not met, consider
changing to alternative insulin regimen
New inclusion
If goals are not met, consider
changing to alternative insulin regimen
Option to switch between fully intensified
regimens when treatment goals not met
Dotted line removed
Change to premixed insulin twice daily (before
breakfast and supper)
Inclusion of TID as an intensification option
If A1c is not controlled,
advance to 3rd injection
Change to premixed analog insulin 3 times
daily (breakfast, lunch, supper)
Start: Add additional injection before lunch
Adjust:  dose(s) by 1-2 units or 10-15% once or
twice weekly to achieve SMBG target.
For Hypo: Determine & address cause; if no clear
reason for hypo,  dose by 2-4 units or 10-20%
ADA 2018
Strong recommendation for premix insulins

Twice daily premix insulins are recommended for

intensification following failure of basal insulin.

Three times daily premixed analog insulins

recommended to be non-inferior to basal-bolus
regimen.

ADA 2018. Diabetes Care 2018 Jan; 41 (Suppl 1)

IDF guideline

IDF treatment algorithm for people with type 2 diabetes. www.idf.org/treatment-algorithm-people-type-2-diabetes

Options to intensify insulin therapy

Basal-plus
regimen
Basal regimen
Basal-bolus
regimen
Once daily premix insulin
regimen
Twice daily premix
insulin regimen
Twice daily premix insulin
regimen

Thrice daily premix

insulin regimen

Strachan MJ, Frier BM. Insulin Therapy: A Pocket Guide. London, Eng-land: Springer-Verlag; 2013; Crasto W, Jarvis J, Davies M. Handbook of Insulin Therapies. Cham: Springer International Publishing; 2016
Agenda

Insulin Barriers Guidelines

Intensification: to insulin on insulin Case based
Rationale & intensification intensification discussion
Definition
Case Study 2A

Case 55-year-old Mr Ravi

Occupation Teacher
Year 2010  Diagnosed with type 2 DM (HbA1c8.3%).
 Good control for 2 years with Metformin
Year 2012 HbA1c7.3%, Sitagliptin added
Year 2014  Deteriorating control (HbA1c 8.6%)
 Initiated with Insulin glargine (OD).
 Initially good HbA1c achieved (7.1%) gradually  7.8%.
 Glargine dose increased to 32 U with further worsening of glycemic control.
Chief complaints  Hypoglycemic episodes during night time
 Loss of classroom confidence.
 Lowered his total daily insulin intake to avoid Hypos.

Current status Incidence of hypoglycemia have reduced, but HbA1c 9.0%.

PPG – 230 mg/dl
Case Study 2A

Interactive question
Options:
Accept the situation

Renew education

Change to premix analogue bid

Change to basal–plus regimen

Other
Basal-plus regimen

Advantages Disadvantages

 Greater HbA1c reductions  Offers PPG control only at 1 meal

compared to basal-only
 Two different insulins requiring
insulin regimen
two separate pens, two separate
 Offers a step-wise approach injections
to insulin intensification
 Chances of confusion between
 Low risk of hypoglycaemia pens and Difficulty in
compared to a basal–bolus distinguishing effect of two
regimen separate insulins in case of
hypoglycaemia

Strachan MJ, Frier BM. Insulin Therapy: A Pocket Guide. London, Eng-land: Springer-Verlag; 2013; Crasto W, Jarvis J, Davies M. Handbook of Insulin Therapies. Cham: Springer International Publishing; 2016
Twice daily premix insulin regimen

Advantages Disadvantages

 Easy to learn and implement while  There is less flexibility

initiating insulin
 Fixed daily routine with regards to
 It has potential for better post-prandial lifestyle, carbohydrate content and
glucose control at 2 meals even during meal timing is required
initiation of insulin therapy
 There is time delay of injection with
 Is more effective in lowering HbA1c conventional mixture (need to inject
than basal insulin alone because of 20 - 30 minutes before a meal)
additional PPG control

Strachan MJ, Frier BM. Insulin Therapy: A Pocket Guide. London, Eng-land: Springer-Verlag; 2013; Crasto W, Jarvis J, Davies M. Handbook
of Insulin Therapies. Cham: Springer International Publishing; 2016
Case Study 2A
How did Mr Ravi fare?

Switched to BIAsp 30 bid plus metformin

Diabetes No Reports a
No HbA1c
& insulin hypoglycemic return of
snacking reduced to
education events classroom
7.4%
imparted confidence
Case 2B : Intensification of insulin therapy

 57 year old Arjun working as an architect and has 12 years history of

diabetes
Relevant history  Metformin was started just after diagnosis with subsequent addition of
gliclazide

 Insulin glargine was started with metformin alone to achieve glycaemic

control
 He underwent an abdominal surgery and was put on basal bolus therapy
Treatment
on discharge along with metformin
 Glargine 32U,
57 year old Male  Regular insulin 10-8-10 U
 Frequent daytime hypoglycaemia. Started defensive eating. Periodically
Patient lowered total daily insulin.
Characteristics  HbA1c - 8.5 %.
 FPG - 184 mg/dL
 PPG - 220 mg/dL

FPG – Fasting plasma glucose; PPG – Post-prandial (breakfast) plasma glucose

Case 2B: Intensification of insulin therapy

Diagnosis

01 02

Type 2 diabetes Hypoglycemia

What options do we have?
Case 2B: Intensification of insulin therapy

Interactive question

Shift to premix analogue insulins TID

Shift to analogue Basal bolus regimen

Shift to IDegAsp twice daily

Other
Basal-bolus insulin regimen

Advantages Disadvantages

 Offers optimum flexibility in terms of  Requires multiple insulin injections

diet and activity
 More complicated to support and
 Potential for better metabolic control if teach and needs carbohydrate
used optimally counting
 Closely mimics normal physiology  Problems of hypoglycaemia and
weight gain
 Potential for the best control of basal
and postprandial hyperglycaemia  Needs full patient motivation and
Requires regular monitoring
 Potential for better lifestyle choice

Strachan MJ, Frier BM. Insulin Therapy: A Pocket Guide. London, Eng-land: Springer-Verlag; 2013; Crasto W, Jarvis J, Davies M. Handbook of Insulin Therapies. Cham: Springer International Publishing; 2016
Case 2B: Intensification of insulin therapy

Treatment
 Along with metformin, therapy with IDegAsp was
initiated with 32 units equally divided between
breakfast and dinner (16-0-16).

 IDegAsp was titrated to 18-0-20 over 4 weeks

 At the end of 4 weeks, FPG = 130 mg/dL.

PPG = 170 mg/dL

Case 2B: Intensification of insulin therapy

IDegAsp was further titrated and at the end of 8 weeks, treatment with IDegAsp :
20-0-22
 FPG = 116 mg/dL
 PPG = 156 mg/dL

At 12 weeks,

 No hypoglycaemia
 Better compliance
 FPG 108 mg/dl
 HbA1c 7.1%
 Case 2B: Intensification of insulin therapy

At the time of
4 weeks 8 weeks 12 weeks
initiation

16-0-16
Insulin dose units 18-0-20 IDegAsp 20-0-22 IDegAsp 22-0-22 IDegAsp
IDegAsp
FPG (mg/dL) 184 130 116 108

PPG
220 170 156 122
(post- breakfast)(mg/dL)

HBA1c (%) 8.5 - - 7.1

Weight (kg) 89 90 91 91

FPG – Fasting plasma glucose;

Key Learnings

The overall aim is to achieve glucose

levels as close to normal as possible

As glycemic control deteriorates over time, insulin

intensification becomes inevitable

Intensifying options include basal-plus, basal-bolus or

premix analogue insulin regimens/co-formulation

Intensifying with co-formulation BID provides effective glycemic

control in a simplified manner compared to basal-bolus therapy
Thank You