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Consensus on Insulin Dose and Titration Algorithms in Ambulatory Care of

Type 2 Diabetes in India

Article  in  The Journal of the Association of Physicians of India · February 2017

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 Journal of The Association of Physicians of India ■ Vol. 65 ■ February 2017 17

ORIGINAL ARTICLE

Consensus on Insulin Dose and Titration

Algorithms in Ambulatory Care of Type 2
Diabetes in India
CID-2015 Expert Group
Rajiv Kovil1, Manoj Chawla2, Rajesh Rajput3, AK Singh4, Binayak Sinha5,
Samit Ghosal 6, Piya Ballani7, Sunil Gupta 8, Snehal Tanna9, SM Bandukwala9,
Tejas Shah 9, Vijay Negalur10, Anil Bhoraskar11, SR Aravind12, Abdul H Zargar13,
Jothydev Kesavadev14, Ashok Kumar Das15

Abstract
Introduction: Insulin is the oldest of the currently available treatment options in Type 2 diabetes mellitus (T2DM)
and is considered as the most effective glucose lowering agent. Despite this, decision on starting insulin therapy is
often delayed in India as well as worldwide due to various barriers at both patient and physician levels. Appropriate
insulin dosing and titration is also critical to the successful achievement of tight glycaemic control.

Objective: To provide simple and easily implementable guidelines to primary care physicians on appropriate
insulin dosing and titration of various insulin regimens for both initiation and intensification.

Methodology: Each insulin regimen (once daily [OD] basal, OD, twice daily and thrice daily premixed, basal-plus
and basal-bolus) was presented and evaluated for dosing and titration based on established guidelines, data from
approved pack inserts, and published scientific literature. These evaluations were then factored into the national
context based on the expert committee representatives patient-physician experience in their clinical practice and
common therapeutic practices followed in India.

Results: Recommendations for dosing and titration of basal, basal-plus, premixed and basal-bolus insulins were
developed. The key recommendations are that insulin doses can be adjusted once or twice weekly; adjustment
can be based on lowest/mean of three recent self-monitoring of plasma glucose pre-meal/fasting plasma glucose
(FPG) values. The titration should be based on FPG or pre-meal value of 80-130 mg/dL and the dose should be
reduced by 10-20% for patients reporting hypoglycaemia(<70mg/dL).

Conclusion:The consensus based recommendations mentioned in this paper will be a useful reference tool for
health care practitioners, to initiate, optimise and intensify insulin therapy and to successfully achieve optimal
glucose control.

1
Consultant Diabetologist, Kovil Diabetes Center, Mumbai; 2Consultant Diabetologist, BSES Municipal General Hospital, Mumbai; 3Senior Professor & Head,
Dept of Endocrinology, PGIMS, Rohtak; 4Consultant Endocrinologist, GD Hospital and Diabetes Institute, Kolkata; Sun Valley Diabetes Research Center,
Guwahati; 5Consultant Endocrinologist, AMRI Hospital, Kolkata; 6Consultant Endocrinologist ,Nightingale Hospital, Kolkata; 7Consultant Endocrinologist
and Diabetologist, Bombay Hospital and Medical Research Centre, Mumbai; 8Consultant Endocrinologist, Diabetes Care Center, Nagpur; 9Consultant
Diabetologist Mumbai; 10Consultant Endocrinologist, Mumbai; 11Consultant Diabetologist , Asian Heart institute & SL Raheja Hospital Mumbai; 12Director
& Chief Diabetologist, DIACON Hospital, Bangalore; 13Consultant Endocrinologist, Srinagar; 14CEO and Director, Jothydev’s Diabetes Research Center,
Trivandrum; 15Professor of Medicine and Professor and Head of Endocrinology, Pondicherry Institute of Medical Sciences, Pondicherry
Received: 07.11.2016; Accepted: 01.12.2016
18 Journal of The Association of Physicians of India ■ Vol. 65 ■ February 2017
Introduction
T ype 2 diabetes mellitus (T2DM)
is the fourth most common
disease worldwide associated
with significant morbidity and
mortality. The incidence rates are
dramatically rising in developing
countries; the reason may be fast
population growth, ageing and
urbanization. It is estimated that by
2025, 70% of people with diabetes
will be from the developing
countries (Mohan and Shah 2014).
As per International Diabetes
Federation (IDF) Diabetes Atlas 7 th
edition, second highest percentage
of diabetic population in the world
resides in India and the number
is estimated to increase from 69.2
million (2015) to 123.5 million by
2040. Diabetes accounts for 14.5%
of global all-cause mortality among
people of age group 20 and 79
years and the highest number of
deaths due to diabetes occurs in
China, India, USA and the Russian
federation (IDF Atlas 2016).
Insulin is the oldest and best
available treatment for managing
T2DM and maintaining normal
glycaemic levels. It can reduce the
glycaemic values from any level to
the recommended glycaemic targets
unlike oral antidiabetic drugs
(OADs). A list of currently available
insulins for the management of
diabetes has been summarized
previously (Das et al 2015). The
choice of insulin regimens depends
o n va r i o u s f a c t o r s , i n c l u d i n g
baseline glycosylated haemoglobin
(HbA1c), duration and type of
diabetes, age of the patient,
hypoglycaemia and weight gain
(Mooradian et al 2006; Nathan et
al 2009). Most of the basal insulins
are dosed at bedtime and titrated
on the basis of fasting plasma
glucose (FPG). Most of the premix
insulins are dosed as pre-meal
twice daily and titrated based on
pre-meal glucose levels. Short
acting insulin analogues provide
mealtime flexibility and are dosed
pre-meal and titrated based on
2-hour postprandial glucose (PPG).
However, despite the benefits
of insulin, primary care physicians
(PCPs) in Indian clinical settings
are found to be less interested
in initiating and intensifying
insulin therapy. In a survey of
600 physicians across 6 countries,
complex guidelines for insulin
optimization/titration was
recognized as the most common
barrier for PCPs (Polinski et al
in 2012). Approximately 30%
of PCPs never/rarely intensify
insulin therapy versus 4% of
s p ec ialist s; t he reason may b e
lack of experience or lack of time
to educate people (Cuddihy et al
2011). In a large multicentre study,
effective glycaemic control (HbA1c
target <7%) was only achieved
in 19.7% of Indian patients with
mean HbA1c as 8.9 ± 2.8%. Of these
patients, 74.8% were on OADs
only and 35.2% of the patients
were on insulin therapy. The poor
glycaemic control suggested a
need for improvement of insulin
dosing and titrations used in Indian
scenario (Mohan and Shah 2014).
Several major guidelines like
American Diabetes Association
(ADA)/European Association for
the Study of Diabetes (EASD) 2016,
Indian National Consensus Group
(INCG) 2013 and IDF 2012 focus
on insulin dosing and titration
differently. Various clinical trials
and clinical trial-based guidelines,
based on insulin titration, have
postulated different titration
algorithms for insulin dosing. Lack
of uniformity in the guidelines
and titration algorithms further
complicates and presents a great
challenge in the management of
T2DM. In order to facilitate the
development of a consensus on
insulin dosing and titration, a
group of experts from across India
held a consensus meeting on 16
April 2016 in Mumbai, India on the
side-lines of CID 2016 conference
in Mumbai. The objectives of the
meeting were to:
• Evaluate the available dosing
regimens and titration
algorithms for currently
available insulins
• Examine the existing evidence
for dosing and titration from
currently available insulins
• Evolve a consensus/unified
statement of recommendations
for dosing and t it ra t i on of
currently available insulins
based on published guidelines,
evidence, package inserts
and clinical experience,
which are simple and easily
implementable
Methodology
During the consensus meeting
on insulin dosing and titration, the
expert group committee discussed
the following insulin regimens
and proposed recommendations
for dosing and titration: once
daily (OD) Basal, OD premix/co-
formulation, twice daily (BID),
and thrice daily (TID) Premix/
co-formulations, Basal-plus and
basal-bolus insulin regimen
(Figure 1). Each insulin regimen
wa s p r e s e n t e d a n d e va l u a t e d
for dosing and titration based
on established guidelines (from
globally recognised professional
bodies as well as those published
within India), data from either
approved pack inserts, prescribing
information or summary of product
characteristics for each insulin type
and published scientific literature.
These evaluations were then
factored into the national context
based on the expert committee
representatives’ patient-physician
experience in their clinical
practice and common therapeutic
practices followed in India. The
e va l u a t i o n s we r e d e b a t e d a n d
discussed within the expert group
committee. The final consensus-
b a s e d r e c o m m e n d a t i o n s we r e
proposed and collectively recorded
for each insulin regimen in easily
implementable steps, without any
bias and in an as much as possible
unambiguous language. At the
end of the meeting, the expert
committee arrived at 6 consensus-
 Journal of The Association of Physicians of India ■ Vol. 65 ■ February 2017 19

Insulin Therapy Situation

1: Dosing and Titration of
Once Daily Basal Insulin
Multiple daily
injection regimens
Regimen
Basal insulin is meant to provide
a c o n s t a n t ‘ b a c k g r o u n d ’ l e ve l
of insulin that controls hepatic
glucose output ( Joshi and Joshi
2009, Justin text book reference).
Currently, Neutral Protamine
Hagedorn (NPH), (Insulatard ® )
G l a r g i n e ( L a n t u s ®) , D e t e m i r
(Levemir ®) and Insulin Degludec
(IDeg) (Tresiba ®) are available in
Fig. 1: Insulin regimens Indian market. IDeg is the latest
ultra-long acting basal insulin
CID 2016 Expert Recommendation
analog with all the properties of an
Expert group recommendation 1: Dosing and Titration of Once Daily Basal Insulins ideal basal insulin i.e. flat peakless
Recommendation on Dose profile, low variability, OD dosing,
• It is recommended to start basal insulins (Degludec/Glargine/Detemir) as 10U once daily flexible timing of administration,
at bedtime
lower nocturnal hypoglycaemia.
• The recommended target for titration is FPG of 80-130mg/dL
Current place in Guidelines/
• It is recommended to titrate the dose once in a week based on FPG Recommendations
• It is recommended to modify dose based on the lowest/mean value of the three most
recent FPG values ADA 2016 recommends initiation
• It is recommended to reduce the dose by 10-20% for patients reporting hypoglycaemia of basal insulin at 10U or 0.1–0.2U/
(<70mg/dL) kg/day depending on the degree
Recommendation on Titration of hyperglycaemia. The doses may
FPG*(mg/dL) Dose adjustments (Units) be titrated (2-4U or 10-15%) once
<80 -2 or twice weekly to reach the target
80-130 0 fasting blood glucose (FBG). In case
131-160 +2 of hypoglycaemia, the dose can be
161-180 +4 reduced by 4U or 10-20%.
>180 +6
The AACE/ACE consensus
*Lowest/mean of the three recent SMPG values; FPG: fasting plasma glucose; SMPG: self-
statement 2016 recommends
measured plasma glucose
initiation of basal insulin based
based recommendations for dosing management of diabetes in primary on HbA1c level <8% (total daily
and titration of insulin regimens. care by the INCG and/or Chapter dose [TDD] 0.1-0.2U/kg) and >8%
The global and national 51 of Indian National Consensus (TDD: 0.2-0.3U/kg). The dose
guidelines and widely accepted and Group-National guidelines on may be titrated every 2-3 days
evaluated consensus statements initiation and intensification of to reach the glycaemic goal. In a
(evaluated by the expert group) insulin therapy with Premixed fixed regimen, they recommend to
include ADA Standard of Care Insulin Analogues (henceforth increase the TDD by 2U whereas in
2016 (written hence forth as ADA written as INCG guidelines), an adjustable regimen, the insulin
2016), consensus statement by the and Consensus evidence-based doses can be adjusted by adding
American Association of Clinical guidelines for insulin initiation, 20% of TDD, 10% of TDD, and
Endocrinologists (AACE) and optimization and continuation 1U for corresponding mean FBG
American College of Endocrinology in T2DM published by Journal of >180mg/dL, 140 to 180mg/dL, and
(ACE) on the comprehensive T2DM Association of Physicians of India 110 to 139mg/dL respectively. In
management algorithm 2016 (written hence forth as Journal case of hypoglycaemia, TDD can be
Executive Summary (written hence of the Association of Physicians reduced by 10-20% and 20-40% for
forth as AACE/ACE Consensus of India [ JAPI] 2014 consensus FBG values <70mg/dL and <40mg/
statement 2016), Global guideline guidelines). dL, respectively. They recommend
for T2DM IDF (written hence forth as the use of basal insulin analogues
IDF 2012), Premix insulin initiation over NPH and to either discontinue
and continuation guidelines for
20 Journal of The Association of Physicians of India ■ Vol. 65 ■ February 2017

Table 1: Approved recommendation on dosing and titration of basal insulin as per titration algorithms is provided in
pack inserts Table 2.
Insulin Onset of action (min) Titration to be done Titration
Peak action(h) based on recommendation in Insulin Therapy Situation
Duration(h) pack insert 2: Dosing and Titration
Neutral 1.5 No specifications No specifications
Protamine 4-12 of Once Daily Premix/
Hagedorn
(Insulatard®)
24
Co-formulation Insulin
Glargine 2-4 No specifications The dose should Regimen
(Lantus®) No Peaks be adjusted and
Upto 24 individualized Current place in Guidelines/
according to BG Recommendations
measurements.
IDF recommends initiation of
Detemir 2 Pre-breakfast BG Simple self-titration
(Levemir®) No Peaks >110+3U premix insulin when first and
Upto 24 80-110No change second line therapies fail to achieve
<80- -3U glycaemic target of HbA1c <7% (IDF
Degludec 1-2 FPG Individual dose 2012). The INCG guideline suggests
(TRESIBA) No Peak adjustments initiation of insulin therapy with
42
OD premix insulin as an add on
BG: Blood glucose; FPG: fasting plasma glucose
therapy to metformin when HbA1c
CID 2016 Expert Recommendation is >7.5% and ≤8.5% (Das et al 2013).
Expert group recommendation 2: Dosing and titration of once daily premix insulin / co- The guideline also recommends to
formulation regimen initiate premix insulin therapy at a
Recommendation on Dose starting dose of 10U either before
• It is recommended to start premixed insulins (BIAsp 30/70, Lispro mix 25/75, BHI 30/70) breakfast, if pre-dinner glucose
as 10U once daily at pre-breakfast or pre-dinner is high or before dinner, if the
• The recommended target for titration is pre-meal value of 80-130mg/dL, pre-breakfast prebreakfast glucose is high. The
dose to be modified, if titrated based on pre-dinner values and vice-versa.
dose should be split when the dose
• It is recommended to titrate the dose once in a week based on pre-dinner or pre-breakfast
is >30 U. Addition and progressive
values
intensification of premixed analogs
• It is recommended to modify dose based on the lowest/mean value of the three most
recent pre-breakfast/pre-dinner values from OD to TID is recommended
• BIAsp 30/70 and Lispro mix 25/75 can be given immediately before the meal, while BHI for better glycaemic control,
needs to be given 30 minutes before the meal particularly when HbA1c≥9%.
• It is recommended to reduce the dose by 10-20% for patients reporting hypoglycaemia While intensifying the dose from
(<70mg/dL) OD to BID, it is recommended
Recommendation on Titration to split the OD dose into equal
Pre meal*(mg/dL) Dose adjustments (Units) breakfast and dinner that is to
<80 -2 be taken before the meals. When
80-130 0 intensifying the dose from BID to
131-160 +2 TID, consider addition of 2-6U or
10% of TDD before lunch which
161-180 +4
may require down titration of
>180 +6 morning dose. As per National
*Lowest/mean of the three recent SMPG values; FPG: fasting plasma glucose; SMPG: self- Institute for Health Care Excellence
measured plasma glucose guideline, OD premix insulin to
be considered when HbA1c level
or reduce sulfonylurea after the the basal insulins are provided in
is ≥9%. Indian premix guideline
start of basal insulin. Table 1.
also considers premix insulin as
Approved Pack Insert on Published Scientific the preferred mode of initiating
and intensifying therapy (Shah et
Dosing and Titration Evidence al 2014; Das et al 2013).
Mo st a ppr o ve d p ac k in s erts Summary of published evidence Approved Pack Inserts on Dosing and
recommend the starting dose of from several clinical trials, which Titration
basal insulin as 10U or 0.2-0.3U/ evaluated basal insulins (NPH, Most pack inserts recommend
kg/day. IDet pack insert provides a Insulin Glargine [IGlar ], Insulin the starting dose of premix
simple and easy titration algorithm. Detemir, or IDeg) using different insulin as 10-12U or 0.2-0.3U/
The titration recommendations of kg/day. The dosing and titration
 Journal of The Association of Physicians of India ■ Vol. 65 ■ February 2017 21

Table 2: Summary of published evidence for dosing and titration: basal insulin regimen
Author & Study Population Target and SMPG value Starting dose Titration algorithm followed
Studies with NPH as an intervention
• Start dose of NPH as 10U
• FPG as target for titration based on mean values
Riddle et al 2003 FPG ≤100 mg/dL 10U/day 100–120  + 0–2U
N=756 Titration based on mean FPG (mg/dL) over 120–140  + 4U
previous 3 days 140–180  + 6U
≥180  + 8U
Only if no plasma glucose
< 56 mg/dL
Hermansen et al 2006 FPG ≤108 mg/dL 10U/day >180  + 10U
N=476 Titration based on mean FPG (mg/dL) over 163–180  + 6U
previous 3 days 145–162  + 4U
109-144  + 2U
In case of pre-breakfast plasma glucose:
56–72  - 2U,
<56  - 4U
Studies with IGlar as an intervention
• Start dose of IGlar as 10U
• FPG as target (100 mg/dL) for titration based on mean values
Davies et al 2005 FPG ≤100 mg/dL 10U/day 100–120  + 0–2U
N=4961 Titration based on mean FPG (mg/dL) over 120–140  + 4U
previous 3 days 140–180  + 6U
≥180  + 8U
Only if no plasma glucose
< 72 mg/dL
Kennedy et al 2006 FPG ≤100 mg/dL 10U/day 100–119  + 0–2U
N=7893 Titration based on mean FPG (mg/dL) over 120–139  + 2U
previous 2-4 days 140–159  + 4U
160–179  + 6U
≥180  + 8U
<70  dose  to previous level
Severe hypoglycaemia  stop upward titration
for 1 week
Studies with IDet as an intervention
• Start dose of insulin Detemir as 10U
• FPG as target (80-110mg/dL) for titration based on mean values
Hermansen et al 2006 FPG ≤108 mg/dL 10U/day >180  + 10U
N=476 Titration based on mean FPG (mg/dL) over 163–180  + 6U
previous 3 days 145–162  + 4U
109-144  + 2U
In case of pre-breakfast plasma glucose:
56–72  - 2U
<56  - 4U
Meneghini et al 2007 FPG 80–110mg/dL 0.32–0.34U/kg <80  -3U
N=5604 Titration based on mean FPG (mg/dL) over 80–110  No change
previous 3 days >110  +3U
Studies with IDeg as an intervention
• Start dose of IDeg 10U
• FPG as target (71-90mg/dL) for titration based on lowest/mean value
Vora et al 2015 FPG goal individualized as per patient needs. 10U/day Below FPG goal: -2U
Titration based on mean FPG (mg/dL) over At FPG goal: Maintain same dose
previous 3 days Above FPG goal: +2U
Zinman et al 2011 FPG 71–90 mg/dL 10U/injection <56  -4U (If dose >45U, reduce by 10%)
N=245 Titration based on lowest value of FPG (mg/dL) 56–71  -2U (If dose >45U, reduce by 5%)
over previous 3 days 71-89  no change
90–125  +2U
126-143  +4U
144-161  +6U
FPG: fasting plasma glucose, IDeg: Insulin Degludec, IDet: Insulin Detemir; IGlar: Insulin Glargine, NPH: Neutral protamine hagedorn, SMPG:
Self monitored plasma glucose

recommendation for OD premix (IDegAsp) is the first soluble co- g l y c a e m i c c o ve r a g e . I D e g A s p

insulin regimens and co- formulation, which combines two contains 30% of short-acting
formulations are provided in Table insulin analogues and provides analogue insulin aspart (IAsp)
3. Insulin degludec/insulin aspart effective basal and prandial and 70% ultra-long-acting basal
22 Journal of The Association of Physicians of India ■ Vol. 65 ■ February 2017

Table 3: Approved recommendation on dosing and titration of once daily premix insulin/co-formulation insulins as per pack
inserts
Insulin Onset of action (min) Dose as approved in Time of Switch from Titration to be done Titration
Peak action(h) pack insert administration existing insulin based on which recommendation in
Duration(h) regimen SMBG value pack insert
Lispro 75/25 0.25-0.5 0.3U/kg Immediately before To be done under No specifications No specifications
1.3-12 a meal (within 15 strict medical
12-24 minutes). When supervision. May
necessary, can be require a change in
given soon after a dosage
meal.
Biasp 30/70 10-20 12U at dinner Immediately before
From BHI, same Pre- meal BG value <80  -2U,
1-3 a meal. When dose and regimen. 80-110  0U,
12-24 necessary, can be
From other insulin, 110-140  +2U,
given soon after a
may require an 141-180  +4U,
meal. increased number >180  6U
of daily injections or
a change in dosage
from that used with
their usual insulin
products
IDegAsp 10-20 10U With the main Unit to unit at the FPG Individual dosage
meal(s). When same total insulin adjustments
1-3 hours needed, timing dose as the patient’s
>24 of administration previous total daily
could be changed as insulin dose. From
long as it is dosed basal/bolus insulin
with the largest meal therapy: based on
(flexibility). individual needs,
generally, on the
same number of
basal units
BG: Blood glucose, FPG: fasting plasma glucose, SMPG: Self monitored plasma glucose

insulin analogue degludec (IDeg).
IDeg and IAsp binds specifically
to the human insulin receptor and
results in the same pharmacological
effects as human insulin. The
basal component (IDeg) forms
soluble multi-hexamers upon
subcutaneous injection, resulting
in a depot from which IDeg is
continuously and slowly absorbed
into the circulation leading to a
flat and stable glucose-lowering-
effect. This effect is maintained
in the co-formulation with IAsp
and does not interfere with the
rapid-acting IAsp monomers, and
hence distinct pharmacokinetic/
pharmacodynamics of the basal
(IDeg) and prandial (IAsp)
components are not compromised
by co-formulation.
Published Scientific Evidence
In India, premix insulin is
the preferred mode of initiating
and intensifying therapy when
b o t h F P G a n d P P G l e ve l s a r e
high (Christiansen et al 2003).
Elevated PPG levels are a
substantial contributor to daytime
hyperglycaemia and its control
is important to achieve optimal
glycaemic control. In a study, OD
premix insulin with Metformin
and/or Glimepiride achieved better
glycaemic control than basal insulin
in insulin-naïve Asian T2DM
patients who were inadequately
controlled with OADs. The self-
monitored blood glucose at
bedtime was also significantly
lower with premix insulin than
basal insulin (p=0.0078) (Kalra
et al 2010). Various other studies
also supported that premix insulin
should be the preferred method of
insulin initiation in ethnic Asian
communities with high levels of
FPG and PPG (Shah et al 2014; Venn
et al 2010; Kalra et al 2010; Wang et
al 2011). Premix insulin provides
a combination of mealtime and
basal insulin in a preset ratio which
may offer an advantage to offset
the PPG excursions. They offer
advantages in terms of 1) simple
start of the injection, 2) option to
easily intensify with same insulin,
3) covers both FPG and PPG
excursions with a single injection,
4) effective HbA1c control, 5) low
incidence of hypoglycaemia and
6) availability in both vials and
device. Premix insulins analogs
have been considered superior to
human premixed insulin in terms
of lower risk of hypoglycaemia
and greater treatment satisfaction
(Davidson et al 2009; Cucinotta
and Russo 2009). The summary of
published evidence from several
clinical trials, which evaluated
dosing and titration of premixed
insulins are provided in Table 4.
Insulin Therapy Situations
3 and 4: Dosing and
Titration of Twice and
Thrice Daily Premix
Insulins
Current place in Guidelines/
Recommendations
ADA/EASD 2016 guidelines
provide the option of transitioning
from basal insulin to BID premix
insulin in patients with T2DM
 Journal of The Association of Physicians of India ■ Vol. 65 ■ February 2017 23

Table 4: Summary of published evidence for dosing and titration: once daily premix insulin / co-formulation insulin regimen
Author & Study Population Target and SMPG value Starting dose Titration algorithm followed
BIAsp studies target FPG (90-110 mg/dL) for titration based on mean value
Strojek et al 2009. FPG 90 - 110 mg/dL 12U/ day <56  –4U
N=480 OD Titration based on mean FPG (mg/ 56–89  –2U
dL) over previous 3 days 90–110  No Adjustment
111–140  +2U
141–180  +4U
≥180  +6U
Raskin et al_2005. Premeal, 80-110 mg/dL. 10U/ Twice daily for FPG<180 mg/dL 80mg/dL  –2U
N = 233 BD Titration based on mean FPG (mg/ 12U/Twice daily for FPG≥180 mg/dL 80-110  No Change
dL) over previous 3 days 111-140  +2U
141-180  +4U
>180  +6U
Lispro studies target FPG (80-109 mg/dL) for titration based on mean value
Fahrbachet al_2008. FPG 80-109 mg/dL. 10U/ Twice daily <80  -2 U
N = 2000 BD Titration based on mean FPG (mg/ 80 – 109  No adjustment
dL) over previous 3-7 days 110 – 139  +2U
140 – 179  +4U
≥180  +6U
IDegAsp studies target Pre-meal (70-90 mg/dL) for titration based on mean value
Onishi et al_2013. FPG 70 - <90 mg/dL. 10U/ day <56  -4 U
N = 296 OD Titration based on mean FPG (mg/ 56 – 69  -2 U
dL) over previous 3 days 70 –<90  No adjustment
90 – <126  +2 U
126 – <144  +4 U
144 – <162  +6 U
≥162  +8 U
Franek et al_2015. FPG 70-90 mg/dL. 06U/ Twice daily <56  –4 (if dose >45 U, reduce by
N = 394 BD Titration based on mean FPG (mg/ 10%)
dL) over previous 3 days ≤70  –2 (if dose >45 U, reduce by
5%)
≤90  No adjustment
<126  +2 U
<144  +4 U
<162  +6 U
≥162  +8 U
FPG: fasting plasma glucose, SMPG: Self monitored plasma glucose

CID 2016 Expert Recommendation insulin doses were calculated by

Expert group recommendation 3: Dosing and titration of twice daily premix insulin / co- splitting the total basal dose either
formulation regimens as 2:1 (2/3 rd of the dose in the
Recommendation on Dose morning [AM] and 1/3 rd of the dose
• When twice daily pre-mix/co-formulation is necessary it is recommended to start at 6U in the evening [PM]) or 1:1 (½ of the
BD at pre-breakfast and pre-dinner dose in the morning and ½ of the
• When shifting from other insulins to premixed, total basal insulin dose to be considered dose in the evening). The doses may
and then administered as two equal doses pre-breakfast and pre-dinner be titrated by 1-2U or 10-15% once
• The recommended target for titration is pre-meal value of 80-130mg/dL, pre-breakfast or twice weekly until self-measured
dose to be modified, if titrated based on pre-dinner values and vice-versa
plasma glucose (SMPG) target is
• Recommended to reduce the dose by 10-20% for patients suffering from hypoglycaemia
reached. In case of hypoglycaemia,
(≤70mg/dL)
the corresponding dose can be
Recommendation on Titration
Pre meal*(mg/dL) Dose adjustments (Units)
reduced by 2-4U or 10-20%. IDF
<80 -2
also recommends intensification
80-130 0 of the therapy from OD premix
131-160 +2 insulin to BID and from BID to
TID (IDF 2012). Both INCG and
161-180 +4
JAPI guidelines recommend the
>180 +6
approach of intensifying premix
*Lowest/mean of the three recent SMPG values; FPG: fasting plasma glucose; SMPG: self-
measured plasma glucose insulin therapy from OD to BID and
TID. INCG guideline recommend
who have failed to reach glycaemic to start the dosing of BID premix intensification of premixed insulin
targets on basal insulin (Inzucchi et insulin as per the previous basal therapy from OD to BID, if HbA1c
al 2015). The guideline recommends insulin dose where the premix >7% and FBG <110mg/dL. If a
24 Journal of The Association of Physicians of India ■ Vol. 65 ■ February 2017
Expert group recommendation 4: Dosing and titration of thrice daily premixed insulin
regimens
Recommendation on Dose
• It is recommended to add 2–6U or 10% of total daily BIAsp 30 dose before lunch for
patients on BID BIAsp 30
• Down-titration of morning dose (2 to 4U) may be needed after adding the lunch dose
• The recommended target for titration is pre-meal target of 80-130 mg/dL
• It is recommended to titrate the dose once in a week based on pre-dinner or pre-breakfast
values
• It is recommended to modify dose based on the lowest/mean value of the three most
recent pre-breakfast/pre-dinner values
patient on pre-mixed insulin
(OD/BID) has HbA1c>7%, though
the pre-meal blood glucose is
within target, intensification to
BID or TID should be considered
(Unnikrishnan et al 2009). When the
TDD of insulin in an OD regimen
nears 40- 50U, the regimen should
be intensified to BID and the
total premix insulin dose should
be split into equal breakfast and
pre-dinner doses (Unnikrishnan
et al 2009). When the single total
insulin dose exceeds 30U, the OD
regimen needs to be intensified to
BID and the total premix insulin
dose should be split into equal
pre-breakfast and pre-dinner doses
(50:50) (Shah et al 2014; Das et al
2013). When BID premix insulin
is to be intensified to TID, 2-6U
or 10% of total daily BIAsp 30
dose before lunch, which may
require downtitration of morning
dose (-2U to 4U), is recommended
(Unnikrishnan et al 2009; Shah et al
2014; Das et al 2013).
JAPI 2014 recommends premix/
co-formulation BID regimen if FPG
is persistently >73-110mg/dL and
Hb-A1c >7% in patients already
receiving OD regimen.
Clinical Practice Guideline
(CDA) 2013 recommends to initiate
premixed insulin at 5-10U OD or
BID (pre-breakfast and/or pre-
supper ). The doses can be titrated
by adding 1-2U to pre-breakfast
and/or pre-supper dose daily
until target pre-breakfast and pre-
supper blood glucose values are
achieved (72-126mg/dL).
Indian insulin guideline
recommends to add 2-6U of BIAsp30
dose at lunch for intensification,
if PPG>180mg/dL and there is a
failure to reach HbA1c<7.
Approved Pack Insert on Dosing and
Titration
M os t approved pack insert s
recommend that premix insulins
can be dosed twice daily. The
pack insert of BIAsp mentions that
it can be dosed OD/BID/TID and
recommends the target of 80-110mg/
dL and titration to be done based
on pre-meal value. The dosing
and titration recommendation for
twice/thrice daily premix regimen
is provided in Table 5.
Published Scientific Evidence
Addition and progressive
intensification of premix insulins
from OD to TID and co-formulation
insulin from OD to TID provides
an easy option for achieving better
glycaemic control and superior
PPG control over adding another
insulin. In an observational “1-2-3
study”, addition and self-titration
of BIAsp 30 once, twice, or thrice
daily enabled 41%, 70% and 77% of
patients to achieve ADA glycaemic
t a r g e t s o f ≤ < 7 % , r e s p e c t i ve l y
(Garber et al 2006).
Franek et al in 2015 reported
the superiority of BID IDegAsp
on FPG control and a reduced
rate of hypoglycaemia compared
with BIAsp 30 in insulin-naive
adults with T2DM. In another
study, T2DM patients uncontrolled
on basal insulin with/without
O A D s ( H b A 1 c l e ve l a s 7 - 1 0 % )
were randomized to IDegAsp BID
or IDeg OD + IAsp 2-4 times daily
over 26 weeks. Though IDegAsp
did not achieve non-inferiority
ve r s u s b a s a l - b o l u s t h e r a p y , i t
was associated with significantly
lower total daily insulin doses, less
weight gain and non-signifcant
l o we r r a t e s o f c o n f i r m e d a n d
nocturnal hypoglycaemia episodes
compared to the basal bolus arm
(Rodbard HW et al 2016). The
summary of published evidence
from several clinical trials, which
evaluated dosing and titration of
premixed insulins are provided in
Table 4.
Insulin Therapy Situation
5: Dosing and Titration
of Basal-Plus Insulin
Regimens
Current place in Guidelines/
Recommendations
ADA/EASD 2016 guideline
recommends to initiate one rapid-
acting bolus insulin injection before
t he larg est meal t o cover P PG
excursions when FPG target is
reached. The bolus insulin dose
can be initiated at 4U or 0.1U/kg
or 10% of basal dose. The bolus
doses can be titrated by increasing
the corresponding dose by 1-2U or
10-15% once or twice weekly until
SMBG target is reached. In case of
hypoglycaemia, the corresponding
dose can be reduced by 2-4U or
10-20%.
The AACE consensus statement
2016 recommends to begin prandial
control initially by adding 1 bolus
injection (10% of basal dose or
5U) before the largest meal (i.e.
Basal-plus 1), which if does not
reach the glycaemic goal, can be
progressively intensified by adding
bolus injections before 2 meals (i.e.
Basal Plus 2) or 3 meals (Basal-Plus
3). The insulin can be titrated every
2-3 days to achieve the glycaemic
goal. The prandial dose can be
increased by 10% or 1-2U, if 2-h
PP or next pre-meal glucose is
consistently >140mg/dL. In case of
hypoglycaemia, the TDD basal and/
or prandial dose can be decreased
by 10%-20% or 20%-40%, if blood
glucose is consistently <70mg/dL
or <40mg/dL, respectively.
CDA 2013 guideline recommends
 Journal of The Association of Physicians of India ■ Vol. 65 ■ February 2017 25

Table 5: Approved recommendation on dosing and titration of twice/thrice daily premix insulin regimens as per pack insert
Insulin Onset of action (h) Dose as approved Time of Switch from Titration to be Titration
Peak action(h) in pack insert administration existing insulins done based on recommendation in
Duration(h) which SMBG value pack insert
Biphasic Human 0.5 The individual An injection When transferring No specifications No specifications
Insulin 30/70 2-8 insulin requirement should be followed from other
24 is usually between within 30 minutes intermediate or
0.3and 1.0 U/kg/ by a meal or long-acting insulin
day. No mention on snack containing medicinal products,
frequency carbohydrates adjustment of the
biphasic human
insulin 30/70 dose
and timing of
administration may
be necessary
Lispro 75/25 0.25-0.5 0.3 U/kg. Does not Immediately before To be done under No specifications No specifications
mention once or a meal (within 15 strict medical
5.8 (1.3-12) twice in the pack minutes). When supervision. May
insert necessary, can be require a change in
12-24 given soon after a dosage
meal
BiAsp 30/70 or 10-20 6 U at breakfast Split the dose into From BHI, same Premeal BG value <80  -2U,
50/50 1-3 and 6 U at dinner equal breakfast and dose and regimen. 80-110  0U,
12-24 (evening meal) dinner doses. 110-140  +2U,
OD/BID/TID 141-180  +4U,
>180  6U
IDegAsp 10-20 10 Units With the Unit-to-unit based FPG Individual dosage
1-3 For Type 1 DM: main meal(s). When on the previous adjustments
>24 OD, 60–70% of the needed, timing bolus insulin
total of administration dose followed by
daily insulin could be changed as individual dosage
requirements. long it is dosed with adjustments
OD/BID the largest meal
. (flexibility)
BID: twice daily, BG: Blood glucose, FPG: fasting plasma glucose, OD: once daily, SMPG: Self monitored plasma glucose, TID: thrice daily
CID 2016 Expert Recommendation level of <180 mg/dL or pre-meal
Expert group recommendation 5: Dosing and titration of basal-plus insulin regimens g lucose level of 72- 1 2 6 mg / d L
Recommendation on Dose before the next meal. It is important
• When intensification with basal-plus is necessary, start one injection at mealtime with the to keep carbohydrate intake
largest meal of the day chosen by patient constant. Oral antihyperglycaemic
• Starting dose is 4U or 10% of basal dose. The prandial insulin dose is recommended to be agents (especially secretagogues)
titrated once a week based on 2-hour post meal value may need to be reduced or
• The recommended target for basal dose titration is FPG of 80-130mg/dL stopped particularly if daytime
• Recommend to reduce the dose by 10-20% for patients suffering from hypoglycaemia hypoglycaemia occurs.
(<70mg/dL)
Approved Pack Insert on Dosing and
Recommendation on Titration of Basal Insulin
Titration
FPG* (mg/dL) Dose adjustments (Units)
<80 -2 Most approved pa c k i n sert s
80-130 0 recommend start dose of basal
131-160 +2 insulins as 10U or 0.2-0.3U/kg/day
161-180 +4 based on individual requirements.
>180 +6 50-70% of total daily insulin dose
Recommendation on Titration of Prandial Insulin may be provided by bolus insulin
PPG* (mg/dL) Dose adjustments (Units) injections and the remainder by
140-180 0 intermediate-acting or long-acting
180-200 +2 insulin. The dosing and titration
200-220 +4 recommendation for basal-plus is
>220 +6 provided in Table 6.
*Lowest of the three recent SMPG values. FPG: fasting plasma glucose; SMPG: self-measured Published Scientific Evidence
plasma glucose; PPG: postprandial plasma glucose
Ampudia-Blasco in 2011
to initiate a single injection of dose of 2-4U/day. The insulin mentioned that the most
bolus insulin prior to either main doses should be titrated by 1U appropriate dose of prandial insulin
meal or breakfast at a starting daily to target 2-hour PPG glucose for any individual patient requires
26 Journal of The Association of Physicians of India ■ Vol. 65 ■ February 2017

Table 6: Approved recommendation on dosing and titration of basal and prandial/bolus insulin as per pack inserts
Insulin Dose as approved for basal plus or Time of administration Switch from existing insulin
basal bolus regimen
Basal insulins
NPH No specifications No specifications No specifications
IGlar No specifications No specifications No specifications
IDet No specifications No specifications No specifications
IDeg No specifications Flexible dosing allowed Unit-to-unit based on the
occasionally when administration previous basal insulin dose
at the same time of the day is followed by individual dosage
not possible, with minimum 8-hour adjustments
gap between 2 doses
Bolus/Prandial Insulins
Human Insulin (Actrapid®) Individualized and determined in An injection should be followed Dosage adjustment may be necessary
accordance with the needs of the within 30 minutes by a meal or snack
patient. Requirement is containing carbohydrates
usually between 0.3 and 1.0 IU/kg/day
Aspart (NovoRapid®) Dosage is individualized and Immediately before a meal or soon Adjustment of dose and a dose of
determined in accordance with the after a meal basal insulin may be necessary
needs of the patient. 50 - 70% of Total
daily insulin may be provided by
NovoRapid® and the remainder by
intermediate-acting or long-acting
insulin.
Glulisine To be Individualized. Total Insulin 15 minute before a meal or within 20 Unit-to-unit based on the
(Apidra®) dose: usually between 0.5 to 1 U/kg/ min after a meal previous bolus insulin dose
day. followed by individual dosage
adjustments
Lispro Individualized based on the route Within 15 minutes before a meal or Unit-to-unit based on the previous
(Humalog ) ® of administration, metabolic needs, immediately after a meal bolus insulin dose followed by
blood glucose monitoring results and individual dosage adjustments
glycaemic control goal.
IDeg: Insulin Degludec, IDet: Insulin Detemir; IGlar: Insulin Glargine, NPH: Neutral protamine hagedorn

defining the target PG value and
adequate dose adjustments through
a titration algorithm. Based on
various studies, they recommended
the starting dose of prandial insulin
(4U or 10% of basal insulin) and dose
adjustments (in sync with ADA/
EASD guideline). Abrahamson and
Peters et al 2012 in their review
article recommended that stepwise
approach may be the easiest to
implement. Gradual introduction
of bolus insulin at mealtimes
helps to ease the transition to
full intensive therapy. They also
suggested that with the evidence of
number of different approaches to
the intensification and optimization
of insulin, ultimately, an approach
that individualizes patient goals
and proceeds conservatively and
renders great care when adding
on and titrating insulin, will help
to increase the success of insulin
therapy in the achievement of
recommended goals (Abrahamson
and Peters 2012).
Table 7 summarizes published
evidence from other clinical trials,
which compared OD regimen
of IDeg or IGlar (Garber et.al
2012) and IGlar/Insulin Detemir
(Hollander et al 2008) with
mealtime insulin aspart in T2DM.
These studies utilized mean of last
3 pre-breakfast and pre-meal SMPG
values for adjusting basal and
prandial insulin doses to achieve
target prebreakfast or pre-meal
S M P G va l u e s . H o l l a n d e r e t a l
in 2008 reported that both basal
insulins, Glargine and Detemir,
with mealtime insulin Aspart were
well-tolerated with no significant
difference in the frequency of
hypoglycaemia or AEs (Hollander
et al 2008). In a study by Garber
et al, IDeg was associated with
lower risks of overall confirmed
hypoglycaemia and nocturnal
confirmed hypoglycaemia than
IGlar in basal-bolus treatment with
mealtime IAsp in T2DM patients
(Garber et al 2012).
Insulin Therapy Situation
6: Dosing and Titration
of Basal-Bolus Insulin
Regimens
Current place in Guidelines/
Recommendations
ADA 2016 guideline recommends
to intensify the insulin regimen
to basal-bolus therapy (≥2 rapid
insulin injections before meals), if
PPG excursions are not controlled
(having achieved FBG target) with
basal-plus regimen or premixed
insulin BID regimen. Bolus or
prandial insulin doses can be
initiated at 0.1U/kg or 4U or 10%
of basal dose/meal. If HbA1c level
is <8%, decrease basal dose by
same amount. The bolus titration
can be done by increasing 2U or
10-15% once or twice weekly until
SMBG target is reached. In case of
hypoglycaemia, the corresponding
insulin doses can be decreased by
2-4U or 10-20%.
The AACE consensus statement
 Journal of The Association of Physicians of India ■ Vol. 65 ■ February 2017 27

CID 2016 Expert Recommendation Approved Pack Insert on Dosing and

Titration
Expert group recommendation 6: Dosing and titration of basal-bolus insulin regimens
Recommendation on Initiation of Basal-Bolus Regimen Pack inserts, for basal insulins
It is recommended to calculate the total insulin dose as 0.3-0.5 U/kg body wt (except for Degludec) have no
40% of the total dose to be given as basal insulins (Degludec, Detemir, Glargine) as a single specifications regarding dose, time
dose at bedtime of administration and switching
60% of the total dose to be given as prandial insulin (Aspart, Glulisine, Lispro) as 3 doses just from existing insulin. For IDeg,
before each meal or just after the meal there are no specifications
Recommendation on Titration of Basal-Bolus Regimen regarding the dose; minimum
The recommended target for titration of prandial component is 2-hour PPG value of <180mg/ 8-hour gap should be there
dL
between the doses and the dose
The recommended target for titration of basal component is FPG value of 80-130 mg/dL
should be individually adjusted.
It is recommended to titrate the dose once in a week based on PPG Pack inserts for bolus insulins
It is recommended to modify dose based on the lowest/mean value of the three most recent recommend individualization of
PPG values
dose requirements. Dosing and
A lower starting dose, slower titration and higher targets may be recommended for those
patients at higher risk of hypoglycaemia
titration recommendation for basal-
Recommendation on Titration of Basal Insulin bolus are provided in Table 6.
FPG* (mg/dL) Dose adjustments (Units) Published Scientific Evidence
<80 -2 The summary of published
80-130 0 e v i d e n c e f r o m s e ve r a l c l i n i c a l
131-160 +2 trials, which evaluated dosing and
161-180 +4 titration of basal-bolus insulins are
>180 +6 provided in Table 7.
Recommendation on Titration of Prandial Insulin Conclusion
PPG* (mg/dL) Dose adjustments (Units) The different insulin regimens
140-180 0 should be tailored to the patient’s
180-200 +2 needs and lifestyle to overcome
200-220 +4 patient related barriers in the
>220 +6 management of T2DM (Petznick
*Lowest of the three recent SMPG values. FPG: fasting plasma glucose; SMPG: self-measured A 2011). The consensus based
plasma glucose; PPG: postprandial plasma glucose recommendations mentioned in
2016 treatment algorithm based on number of meals per day this paper are based on the existing
recommends TDD of insulin (i.e. 20% of prandial insulin 3 times guidelines on insulin regimen and
0.3-0.5U/kg, to be distributed as per day) using either rapid acting adapted from algorithms used in
50% basal insulin and 50% prandial analogue or short-acting insulin. several clinical trials and clinical
insulin. The 50% prandial insulin observations.
JAPI Consensus Evidence-based
dose can be divided based on Guidelines 2014 recommends that Collated review of the
number of meals. Insulin titration all analogue basal-bolus regimen recommendations presented in
can be done every 2-3 days to reach may be considered over all human this consensus on various insulin
the glycaemic goal. Prandial dose basal-bolus regimen for similar regimen can be further simplified
can be increased by 10% or 2U, if reduction in HbA1c with reduced as follows:
2-h PP or next pre-meal glucose is risk of nocturnal hypoglycaemia, • Insulin doses can be adjusted
consistently >140mg/dL. In case of less weight gain and lower day- once or twice weekly
hypoglycaemia, TDD basal and/ to-day within-person variability • Adjustments can be based on
or prandial insulin can be reduced in FPG (Grade A; EL 1) (Raslova lowest/mean of 3 recent SMPG
by 10%-20% and 20%-40%, if blood et al 2004). In a fully optimized pre-meal/FPG values
glucose level is consistently <70mg/ basal-bolus regimen, the TDD of
dL and <40mg/dL, respectively. • F o r O D i n s u l i n r e g i m e n s ,
insulin will resemble a ratio of
the titration should be
CDA 2013 recommends TDD approximately 50% basal insulin
based on FPG or pre-meal
of 0.3-0.5U/kg, which is to be and 50% bolus insulin, divided
value of 80-130mg/dL. It is
distributed as 40% of the total into three equal bolus doses of
recommended to reduce the
insulin dose as basal insulin dose rapid-acting insulin (Riddle et al
dose by 10-20% for patients
and 60% prandial insulin dose (i.e. 2013; Pearson et al 2006; Palumbo
reporting hypoglycaemia
20% of total insulin dose as bolus et al 2004) Regular SMBG levels 2-h
(<70mg/dL)
[prandial] 3 times per day). The postprandial is recommended.
60% prandial insulin dose to be These consensus based
28 Journal of The Association of Physicians of India ■ Vol. 65 ■ February 2017

Table 7: Summary of Published Evidence for Dosing and Titration of basal and prandial/bolus insulin
Author (Study Population) Target and SMPG value Starting dose Titration algorithm followed
Detemir-aspart versus Glargine-aspart
Hollander 2008 Basal:  No algorithm defined Pre breakfast: adjust evening dose
(N = 319) FPG ≤ 108 mg/dL. Target:
Titration based on mean FPG (mg/ <108  0
dL) over previous 3 days 109-126  2U
127-144  4U
145-162  6U
163-180  8U
>180  12U
Prandial: In case of pre-breakfast/pre-dinner
Initiated and adjusted to target 90 plasma glucose:
min PPG ≤ 162 56–72  -2U,
<56  -4U
Degludec-aspart versus Glargine-aspart
Garber AJ et al, 2012 (N = 755) Basal: Glargine arm: Pre breakfast: adjust evening dose
Pre Breakfast 20-30% reduction in basal dose Target:
FPG 70-89 mg/dL. Degludec: <56  -4U
Titration based on mean FPG (mg/ Investigator’s discretion 56-69  -2U
dL) over previous 3 days 70-89  0U
90-125  +2U
126-143  +4U
144-161  +6U
≥162  +8U
Prandial: 4U in bolus naïve patients 70-89  0U
Pre Prandial/ Bedtime plasma 90-143  +2U
glucose 144-179  +3U
Target: 70-89 mg/dL ≥180  +4U
FPG: fasting plasma glucose, PPG: Post prandial plasma glucose, SMPG: Self monitored plasma glucose

recommendations are anticipated
to provide guidance to PCPs and
specialists in treating T2DM. While
selecting the ‘best-match’ insulin
regimen, it is also important that
PCPs and specialists consider the
capacity of insulin to match the
pharmacokinetic parameters of
insulin and physiologic conditions
which they often rely on i.e.
patient’s blood glucose profile (or
glucose trend) derived from their
SMBG measurements ( Joshi and
Joshi 2009; Das et.al 2013).
The strength of the current
consensus is that it has been
developed by giving priority
to experience and common
therapy practices with regard to
Indian context while giving due
consideration to recommendations
from globally acceptable guidelines
and to clinically published
evidences. The final proposed
consensus-based recommendations
we r e c o l l e c t i ve l y r e c o r d e d f o r
each insulin regimen in easily
implementable steps, without any
bias and in an as much as possible
unambiguous language.
The weakness of the consensus
emanates from the fact that it does
not provide guidance regarding
allowance or discontinuation of
OADs and insulin secretagogues
along with various insulin
regimens. The primary purpose of
clinical trials was not to evaluate
the evidence of the algorithm used
in the trial. Hence, interpretation of
the algorithm merit in those cases is
somewhat difficult and has to rely
on cross trial comparisons.
We hope that these consensus
recommendations will be a useful
reference tool for physicians and
that their impact will be validated
through observational research in
real-life practice, involving large
number of physicians and in the
setting of routine outpatient care
of T2DM in India.
However, various factors in
addition to the algorithm used
i n t h e s t u d y we r e a p p a r e n t l y
known to affect the achieved results
such as, the rigor with which the
algorithm is enforced in the study,
whether titrations are health care
provider or patient directed, and
the frequency of dose adjustments.
Additionally, characteristics of the
patients, including how advanced
their disease is and what oral drugs
are concomitantly used and/or
discontinued at the start of insulin
therapy, are important.
Acknowledgement
The authors thank Novo Nordisk
India Pvt. Ltd. for supporting the
conduct of the consensus meeting
and providing writing assistance in
the development of this manuscript.
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