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