supplement to Journal of the association of physicians of india Published on 1st of every month 1st July, 2014 VOL.

62 49

Consensus Evidence-based Guidelines for Insulin

Initiation, Optimization and Continuation in Type 2
Diabetes Mellitus
Siddharth Shah*, SK Sharma**, Parminder Singh***, A Muruganathan****, Ashok Kumar Das*****

Abstract
The prevalence of diabetes continues to increase despite advances in detection and therapy. Majority of the patients
fail to achieve desired glycaemic targets even with maximal tolerated doses of oral anti-hyperglycaemic drugs,
necessitating insulin therapy. Although, much attention has been given to early insulin initiation, yet substantial
proportion of patients do not achieve glycaemic targets as they fail to initiate or intensify insulin therapy at the
appropriate time. The choice of an insulin regimen and timely initiation and intensification of insulin therapy
are key factors in achieving optimal glycaemic control. This current consensus guideline developed by a panel of
experts aims to provide specific recommendations based on existing guidelines and published data on initiation
and intensification of insulin therapy in management of type 2 diabetes mellitus (T2DM) using basal, premixed
and basal-bolus insulin regimens in Indian clinical practice. The panel recognized the need to upgrade the existing
guidelines for management of T2DM and endorsed recommendations that are in line with Indian insulin guidelines.

Introduction 5% to 15% and 2% to 5% among urban and rural populations,

T ype 2 diabetes mellitus (T2DM) is characterized by
progressive loss of insulin secretion from beta cells and
increasing insulin resistance driven by obesity.1 It is estimated
that, by the time diagnosis is done, most patients with T2DM
had lost more than 50% of their beta-cell function which steadily
continues to decline at approximately 3-5% per year.2 Overtime,
even with multiple oral anti-diabetic drugs (OADs) patients fail
to achieve or maintain glycated haemoglobin (HbA1c) levels.3
However, accumulating evidence suggests that the decline in
beta-cell function may be slowed or even reversed, particularly
if addressed early in the course of the disease.4 Nevertheless, the
prevalence of diabetes continues to increase despite advances in
detection and therapy.
Prevalence of diabetes: Global and India
According to recent estimates from International Diabetes
Federation (IDF), approximately 382 million people worldwide
in the 20-79 year age group had diabetes mellitus (DM) in 2013
and by 2035 this number is going to increase to approximately
592 million (7.8%).5 DM is a major health concern in Asian
countries with more than 60% of the worlds diabetic population
living in Asia.6 Prevalence of DM and impaired glucose tolerance
is high for all Asian countries and is expected to increase
further in the next two decades.7 According to IDF, 65.1 million
Indians are affected by diabetes making them the second largest
population in the world; this number is expected to reach 109
million by year 2015.5 New figures from a recent Indian Council
of Medical Research-India Diabetes (ICMR-INDIAB) study
indicate that there are already 62.4 million people with diabetes
and 77.2 million people with pre-diabetes.8 The prevalence of
diabetes varies from 9% to 16.6% in different regions, with higher
prevalence rates in the southern region of India.9 Studies over
the period 1990-2000, indicate a rising trend in diabetes from
*
Consulting Physician and Diabetologist, Bhatia Hospital, Bombay
Mutual Terrace, Mumbai; **Dr. S. K. Sharmas Diabetes Thyroid and
Endocrine Centre, Jaipur; ***Dayanand Medical College and Hospital,
Ludhiana, Punjab; ****A. G. Hospital, 34, K.P.N. Colony, Tirupur;
*****
Department of Medicine, Jawaharlal Institute of Postgraduate
Medical Education and Research, Pondicherry
respectively.9
T2DM: Need for insulin
Glycaemic control is the cornerstone of the management
of T2DM. Generally comprehensive lifestyle management
combined with metformin monotherapy is the recommended
initial therapy for patients with T2DM.10 However, majority of
patients (> 50%) fail to achieve target glucose levels even with
maximal doses of monotherapy,11 requiring intensification of
therapy by addition of one or more pharmacological agents
including insulin.12 When intensifying the existing therapy,
physicians need to elucidate the role of beta cells in insulin
secretion to the patients newly diagnozed with diabetes
and convince them for intensive insulin therapy. Besides,
physician should also consider patient-related issues such as
previous co-morbidities, presence of uncontrolled symptomatic
hypoglycaemia and obesity while prescribing insulin.
Existing guidelines for T2DM
Several international, national and regional guidelines are
available for diabetes management to facilitate physicians
and patients by providing step-wise treatment algorithm
for management of T2DM. They include American Diabetes
Association/European Association for the Study of Diabetes
(ADA/EASD), American Association of Clinical Endocrinologist
(AACE), National Institute of Clinical Excellence (NICE),
International Diabetes Federation (IDF) and Indian National
Consensus Group (INCG) guidelines. Although, the
recommended glycaemic target varies somewhat among the
guidelines, the overall aim is to guide physicians in identifying
components of diabetes care, general treatment goals, and
tools to evaluate the quality of care. Based on results from large
randomized trials,13,14 most of the guidelines emphasise on
aggressive management of diabetes and associated risk factors
for prognosis in T2DM.
Rationale/need for India specific guidelines
Despite evidences supporting the early initiation of insulin
to achieve optimal glycaemic control, yet substantial proportion
of patients do not achieve glycaemic targets as they fail to
intensify insulin therapy. Many patients and physicians are
50 supplement to Journal of the association of physicians of india Published on 1st of every month 1st July, 2014 VOL. 62
reluctant to begin insulin treatment owing to significant
concerns about weight gain, hypoglycaemia and changes in
lifestyle.15-19 Although several guidelines have been published
for the management of T2DM, due to confounding biases and
non-applicability of these guidelines in Indian scenario, these
cannot be widely used in Indian clinical practice. This current
consensus guideline aims to provide specific recommendations
based on published data for proper management of T2DM and
justified for use according to routine Indian clinical practice.
Methodology
A systematic review of literature from medical databases
was conducted to provide the best possible evidence base for
the recommendations. Existing guidelines, metaanalyses,
systematic reviews and key cited articles relating to the
medical condition were reviewed by a group of doctors and
recommendations relevant to Indian scenario were framed.
The recommendations were discussed at the National Insulin
Summit, held in August 2013 by an expert panel of physicians,
endocrinologists and key opinion leaders. At this summit,
recommendations for each section of the guidelines, and overall
recommendations were agreed upon. Where there was little or
no evidence, the committee relied on experience, judgement
and consensus to make their recommendations. The consensus
document was drafted and circulated for further feedback from
the participants and others who could not attend.
Grading system
The current consensus guidelines have been developed in
accordance to the AACE protocol for standardized production
of clinical practice guidelines.20 Recommendations are organized
by topic and are assigned evidence level (EL) ratings on the
basis of the quality of supporting evidence all of which have
also been rated for strength. Recommendations are based on
clinical importance and graded as A (strongly recommend), B
(intermediate), C (weak) and D (not evidence based), those are
coupled by four intuitive levels of evidence: 1,2,3,4. The evidence
levels have been positioned on the basis of available evidence to
be used for grading recommendations as follows :
1: Meta-analysis of randomized controlled trials,
randomised controlled trials
2: Meta-analysis of nonrandomized prospective or
case-controlled trials, nonrandomised controlled trial,
prospective cohort study, retrospective case-control study
3: Cross-sectional study, surveillance study (registries,
surveys, epidemiologic study, retrospective chart review,
mathematical modelling of database), consecutive case
series, single case reports
4: No evidence (theory, opinion, consensus, review, or
preclinical study)
Insulin Therapy in T2DM
Traditionally, insulin treatment for T2DM is usually started
when the initial oral therapy, in double or triple combination
and at the maximum tolerated doses fails to achieve optimal
glycaemic control. However, recent guidelines recommend
initiation of insulin early in the course of disease, especially in
patients with HbA1c > 9% as it is unlikely to achieve glycaemic
targets with the use of oral agents alone.5,21 Data from a recent
meta-analysis indicate that, short-term intensive insulin therapy
for 2-3 weeks have favourable outcomes on recovery and
maintenance of beta-cell function and protracted glycaemic
remission, besides increment in HOMA-B (-cell function)
and decrease in HOMA-IR (insulin resistance) improving the
underlying pathophysiology in early T2DM.22 While baseline
body mass index and fasting plasma glucose (FPG) were
considered to be important clinical predictors to identify these
patients. The current consensus recommendations are in line
with ADA/EASD and IDF guidelines for insulin management
in T2DM.
Recommendations
It is recommended to initiate insulin when HbA1c is more
than 9% even after treatment with maximum tolerated dose
of two or three OADs (Grade A; EL 4).5,21
In newly diagnosed T2DM patients with higher body mass
index and lower FPG, short-term intensive insulin therapy
for 2-3 weeks is recommended for favourable outcomes
on recovery and maintenance of beta-cell function and
protracted glycaemic remission (Grade A; EL 1).22,23
Initiation of insulin therapy-general strategy
Timely initiation of insulin therapy is crucial for optimal
glycaemic control and improved patient outcomes. Although
most physicians agree that insulin is an effective approach in
treating diabetes, many still consider it a last resort due to the
fear of hypoglycaemia and weight gain to their patients.24 The
choice of insulin regimen depends on several factors such as type
of diabetes, duration of diabetes, baseline and current HbA1c
levels, age, existing comorbidities, ability to adhere to medical
instructions, number of injections, hypoglycaemia, weight gain
and frequency of monitoring.25,26
Both AACE/ACE and ADA/EASD guidelines recommend
initiating insulin therapy with basal insulin.20,21 The general
concept is to first correct the fasting hyperglycaemia with
one injection of basal insulin, and then address postprandial
hyperglycaemia, if needed, with other insulin options. Similarly,
IDF recommends initiation of insulin with either basal insulin or
premixed insulin when first line and second-line therapies fail
to achieve glycaemic target of HbA1c < 7.0%.5 INCG guidelines
suggest initiation of insulin therapy with premixed insulin in
newly diagnosed patients with FPG values > 150 mg/dL, PPG
values > 200 mg/dL and HbA1c > 8.5%.27
Recommendations
Both premixed insulin and basal insulin can be considered
as a start insulin in patients with T2DM (Grade A; EL 1).21,27,28
- When FPG is high consider initiating insulin therapy
with basal insulin.29
- When both FPG and PPG are high consider initiating
insulin therapy with premixed insulin.30
Better PPG control in insulin-nave Asian subjects
In India, premixed insulin is the preferred mode of initiating
and intensifying therapy as recommended in the Indian
premix guidelines.27 Studies indicate that PPG is higher among
Asians in response to a realistic carbohydrate load compared
to Caucasians, even in patients with low body mass index.17,31
Given that elevated PPG levels are a substantial contributor to
daytime hyperglycaemia, targeting PPG control becomes crucial
in achieving optimal glycaemic control. Evidence suggests
that in insulin-nave Asian subjects with T2DM inadequately
controlled with OADs, once-daily premixed insulin achieved
better glycaemic control compared to basal insulin. Mean
self-monitoring of blood glucose (SMBG) at bedtime was
significantly lower with premixed insulin than basal insulin
supplement to Journal of the association of physicians of india Published on 1st of every month 1st July, 2014 VOL. 62 51
100 Lifestyle Mono- Dual Insulin oral
therapy therapy drugs for
lowering
Beta-cell function (%)
blood glucose
9
HbA1c (%)
8 premix insulin
7
HbA1c
Beta-cell function
0 6
0 >15
Time (years)
Fig. 1 : Traditional treatment strategy for type 2 diabetes and its
consequences
Abbreviations: HbA1c: glycated haemoglobin
(P = 0.0078).32 Moreover, premixed insulins have been shown
to be superior in decreasing PPG with an added advantage of
lower risk of hypoglycaemia and greater treatment satisfaction
compared to human premixed insulin.33,34 The current consensus
recommendations are in line with INCG guidelines.
Recommendations
In T2DM patients initiating insulin therapy with premixed
analogue insulin than premixed human insulin is
recommended for low risk of hypoglycaemia (Grade A; EL
1).33
Given the evidence that PPG control may be more important
when HbA1c levels are low, premixed insulin analogue
would be most appropriate choice for patients requiring
insulin (Grade A; EL 1).35,36
Since, PPG contribution to hyperglycaemia is more
pronounced in ethnic Asian communities, premixed insulin
that improves PPG should be the preferred method of
insulin initiation in this population when both FPG and
PPG are high (Grade A; EL 1).31,32,35
Initiation with basal insulin therapy
In clinical practice, the most popular scheme for starting
insulin therapy in T2DM is the addition of once daily (OD)
basal insulin to the oral therapy.21 Evidences indicate several
benefits to using basal insulin analogues (insulin detemir
and insulin glargine) over intermediate-acting human insulin
(neutral protamine Hagedorn (NPH) including better glycaemic
control, reduced risk of hypoglycaemia and weight gain.37
Moreover basal insulin analogues have been associated with
lower within-patient pharmacokinetic and pharmacodynamics,
relatively steady rate of absorption and flat profile of action that
extends over a 24-hour period.38 Clinical experience indicates that
with OD administration of the basal insulin analogues, greater
proportion of patients achieved HbA1c < 7.0% compared to basal
human insulin (26 vs. 16%, P = 0.008 respectively). Similarly the
risk for overall hypoglycaemia was reduced by 47% (P < 0.001)
and nocturnal hypoglycaemia was reduced by 55% (P < 0.001)
with basal analogue insulin compared to basal human insulin.37
Insulin degludec is a new basal insulin analogue with a
unique mode of protraction by forming multi hexamers in
subcutaneous space.39 It has a flat and stable glucose-lowering
effect making it an ultra-long acting basal insulin analogue
with half-life of more than 25 hours (twice as long as that for
insulin glargine) and duration of action beyond 42 hours.40
Insulin degludec has a more consistent and evenly distributed
metabolic effect across a 24-hour dosing interval than insulin
glargine. Moreover, its day-to-day variability is considerably
Basal insulin Initiation Premix insulin OD
Intensification
BID BID or TID
Basal-bolus
premix insulin
Fig. 2 : Stepwise insulin intensification strategies for patients with
type 2 diabetes
Abbreviations: OD: once daily; BID: Twice daily; TID: Thrice daily
lower than insulin glargine (up to four times).41 The ultra-long
pharmacokinetic properties of insulin degludec are preserved
in subjects with renal impairment and hepatic impairment.
Insulin degludec can be administered anytime in the day and is
recommended as once daily basal insulin analogue.
Most of the guidelines including IDF, ADA/EASD, NICE
and Chinese Diabetes Society, recommend initiation of
insulin therapy with basal insulin. The current consensus
recommendations are in line with IDF, ADA/EASD, NICE
guidelines for initiation of basal insulin therapy.
Recommendations
In T2DM patients poorly controlled on oral drug therapy
and with high FPG, addition of basal analogue insulin over
basal human insulin is recommended to achieve guideline-
recommended HbA1c with reduced hypoglycaemia and less
weight gain (Grade A; EL 1).37
Intensification of Insulin Therapy
The traditional approach of hyperglycaemia management
follows the sequence of lifestyle modification, monotherapy,
combination therapy with OADs, and finally treatment with
insulin. This results in recurrent failure glycemic control in
patients with T2DM due to the substantial glycaemic burden
carried for years, before therapy is intensified (Figure 1). Thus,
it is prudent to choose interventions that effectively lower
hyperglycaemia and keep glycaemic levels as near to normal
as possible. At this point, insulin supplementation is required
in order to achieve glycaemic control.42
Existing guidelines on intensification
Several guidelines including ADA, EASD, IDF, AACE, NICE
and INCG recommend insulin intensification for the treatment
of diabetes to facilitate good glycaemic control.5,21,27,43,44 Patients
initiated on basal insulin may be intensified to either basal-bolus
therapy or premixed insulin BID. Similarly those initiated on OD
premix insulin therapy may be intensified to BID or TID, which
may be further intensified to basal-bolus therapy (Figure 2).45
Intensification with basal-bolus therapy
Although initiating basal insulin in T2DM patients results
in significant improvement in glycaemic control, therapy
eventually needs to be intensified with the addition of prandial
insulin to achieve desired glycaemic control.46 Randomized
clinical trials investigating the efficacy of basal-bolus regimen
have reported significant improvement in HbA1c, less weight
gain, lower rates of hypoglycaemia and less within-person
variation in blood glucose than basal human insulin or all human
basal-bolus regimen.47-52
In a study comparing efficacy and safety of all analogue
versus all human basal-bolus therapy in T2DM patients, despite
similar reduction in HbA1c (0.65% and 0.58% respectively), the
52 supplement to Journal of the association of physicians of india Published on 1st of every month 1st July, 2014 VOL. 62

basal-bolus analogue regimen was associated with a significantly In a fully optimized basal-bolus regimen, the total daily
lower within-person variation in self-measured fasting plasma insulin dose will resemble a ratio of approximately 50%
glucose (FPG) (SD: 1.20 versus 1.54 mmol/L, P < 0.001) and basal insulin and 50% divided into three equal bolus doses
lower body weight gain (0.51 versus 1.13 kg, p = 0.038) than of rapid-acting insulin (Grade A; EL 2).53-55
with all human basal-bolus regimen. The risk of nocturnal Intensification with premixed insulin therapy
hypoglycaemia was 38% lower with all analogue basal-bolus
Premixed insulin preparations are simple and convenient
regimen than with all human basal-bolus regimen.52 The current
regimen that provide an intermediate acting insulin and
consensus recommendations are in line with ADA/EASD
a short- or rapid-acting insulin within the same injection.
guidelines and published data from clinical trials.
Initiating insulin therapy with premixed insulin OD opens the
Recommendations possibility of a step-wise approach to intensify therapy to BID
All analogue basal-bolus regimen may be considered over all and even TID in patients to achieve target HbA1c levels.45 These
human basal-bolus regimen for similar reduction in HbA1c regimens, however, require patients to adhere to a consistent
with reduced risk of nocturnal hypoglycaemia, less weight meal schedule and carbohydrate intake to avoid prandial hypo-
gain and lower day-to-day within-person variability in FPG and hyperglycaemia. Evidence indicates that in T2DM patients
(Grade A; EL 1).52 failing on oral agents with or without basal insulin, addition and
self-titration of premixed insulin from OD to BID and even TID,
Table 1 : Titration Algorithm for BIAsp 30 based on FPG
could achieve AACE/IDF and ADA glycaemic targets (HbA1c
values
6.5% and < 7%).56 It has been recommended as a treatment
FPG values Dose change strategy in several clinical practice guidelines viz. AACE,
< 4.4 mmol/L < 80 mg/dL -2 U IDF and INCG.ADA/EASD identifies intensification of basal
4.46.1 mmol/L 80110 mg/dL 0 insulin to BID premixed insulin as a less studied alternative to
6.27.8 mmol/L 111140 mg/dL +2 U intensification with basal-plus regimen.21 While IDF recommends
7.910.0 mmol/L 141180 mg/dL +4 U intensification of the therapy if the patient is already using
> 10.0 mmol/L > 180 mg/dL +6 U
premixed insulin from OD to BID or from BID to TID.5 NICE
recommends monitoring of a person who is using pre-mixed
FPG: fasting plasma glucose; U: units

Table 2 : Comparison of recommendations from current consensus guidelines and existing guidelines
Parameter Consensus AACE ADA/EASD IDF NICE INCG
guideline
Glycaemic targets HbA1c < 9.0 HbA1c 6.5 HbA1c 7.0 HbA1c 7.0 HbA1c 7.0 HbA1c 7.0
FPG: < 110 mg/dL FPG: < 110 mg/dL FPG:70-130 mg/dL FPG: < 115 mg/dL FPG: < 110 mg/dL
PPG: < 180 mg/dL PPG: < 140 mg/dL PPG: < 180 mg/dL PPG: < 160 mg/dL PPG: < 180 mg/dL
Initiation with When FPG is high When HbA1c Based on degree Initiate using a self- Consider basal Does not
basal insulin (> 150mg/dL); 8.0% initiate OD at of hyperglycaemia titration regimen insulin analogue in recommend
therapy Consider initiation 0.1 -0.2 U/kg body initiate at 0.10.2 U/ i.e. 2 units increase patients with severe initiation with basal
with basal analogue weight; kg body weight in dose for every 3 hypoglycaemia insulin
insulin When HbA1c 8-10% days
initiate at 0.2-0.3 U/
kg body weight
Initiation with When both FPG and Initiate in patients Initiate BID in Initiate OD or BID Consider OD or BID Initiate OD as add
premixed insulin PPG are high requiring simpler patients with higher based on degree of pre-mixed human on to metformin
therapy (> 150 mg/dL regimen or finding HbA1c levels hyperglycaemia insulin if HbA1c when HbA1c level
and > 200 mg/dL difficulty with ( 9.0%) 9.0% are > 7.5% and
respectively) basal-bolus therapy 8.5%
Intensification with Consider all Intensify in patients Intensify basal or premixed insulin therapy to basal-bolus No recommendation
basal-bolus therapy analogue basal- with symptomatic therapy; Consider prandial insulin when PPG is high available
bolus regimen; hyperglycaemia and (> 180 mg/dL)
Regular SMBG HbA1c > 10%.
levels 2 hours
after meals is
recommended
Intensification with Intensify from OD No recommendation Intensify basal Intensify therapy if already using Intensify from
premixed insulin to BID/TID; Split available insulin to a BID premixed insulin from OD to BID or OD to BID, when
therapy the OD dose into premixed insulin from BID to TID HbA1c > 8.5%
equal breakfast and If HbA1c > 7% and
dinner doses (50:50); FPG > 100 mg/dL,
when intensifying titrate from OD to
BID to TID up BID till FPG levels
titrate lunch dose < 100 mg/dL
and down titrate
morning dose
Abbreviations : ADA, American Diabetes Association; EASD, European Association for the Study of Diabetes; AACE, American Association of Clinical Endocrinologist;
IDF, International Diabetes Federation;NICE, National Institute of Clinical Excellence; INCG, Indian National Consensus Group; HbA1c, Glycosylated haemoglobin;
FPG, Fasting plasma glucose; PPG, Postprandial plasma glucose; OD: Once daily; BID: Twice daily; TID: Thrice daily; SMBG, self-monitoring of blood glucose
supplement to Journal of the association of physicians of india Published on 1st of every month 1st July, 2014 VOL. 62 53

consider adding 26 U or 10% of total daily BIAsp 30

Lifestyle changes + metformin
dose before lunch which may require down titration
If HbA1c 7.0% after 2-3 months of morning dose (-2 to 4 U) (Grade A; EL 4).45

Additional therapy
Premixed insulin vs. basal plus therapy
add sulphonylurea or glitazones or GLP-1 agonist or DPP-4 or alpha Clinical evidences indicate that modern insulin
glycosidase inhibitors or insulin, analogue regimens, adjusted to post prandial glucose
Insulin is recommended if HbA1c > 9% targets, enable a majority of people with T2DM to reach
HbA1c 7.0% after failure of OADs and OAD-basal
High FPG High FPG and PPG
insulin therapy.57 Data from a 24-week, open-label,
Basal insulin OD Premix OD multinational, superiority trial comparing basal plus
vs. premixed insulin in 923 insulin-nave T2DM patients
uncontrolled on OADs suggest that more number of
HbA1c > 7% HbA1c > 7% patients treated with premix insulin achieved superior
HbA1c reduction from baseline (P = 0.008), superior
FPG > 110 mg/dL FPG > 73-110 mg/dL
mean plasma glucose reduction from baseline (P = 0.024)
Titrate basal to achieve FPG Premix BID and more patients reached HbA1c < 7% compared to
< 110 mg/dL
basal plus therapy (27.9% vs. 19.3%).58
Recommendations
FPG and/or pre-dinner FPG and/or pre-dinner BG In insulin-nave patients with T2DM, premixed
BG > 110 mg/dL 73-110 mg/dL insulin regimen twice daily may be considered
similar to basal plus regimen to achieve target
HbA1c (< 7%) without the risk of hypoglycaemia
Titrate Premix BID to achieve FPG HbA1c 7-8% (Grade A; EL 1).58
Failure to
reach
and/or pre-dinner BG < 100 mg/dL
HbA1c < 7%
Summary
If hypoglycaemia occurs Premix TID T2DM is a chronic condition, which requires proactive
escalation of therapy, including early advancement to
Failure to combination therapy and/or insulin use. The choice
reach
HbA1c < 7%
of an insulin regimen and the timing of initiation
and optimization of insulin therapy are key factors in
achieving optimal glycaemic control. Several simple
Basal-bolus therapy and practical algorithms are available to guide patients
Fig. 3 : Proposed algorithm for initiation, optimisation and continuation of and physicians through a step-by-step process of
insulin therapy in patients with type 2 diabetes mellitus initiating and advancing insulin therapy. However,
Abbreviations: HbA1c, Glycosylated haemoglobin; GLP-1 agonist, practical considerations involved with initiation
glucagon like peptide-1 agonist; DPP-4, dipeptidylpeptidase-4, FPG, Fasting and optimization of insulin therapy have to be more
plasma glucose; PPG, Postprandial plasma glucose; OD: Once daily; BID: Twice carefully dealt to achieve glycaemic goals without the
daily; BG, blood glucose; TID: Thrice daily risk of hypoglycaemia and weight gain. Based on the
best clinical observations and recommendations from
insulin OD or BID for the need of short-acting insulin before
existing guidelines and protocols for insulin therapy in T2DM,
meals or change to a regimen of mealtime plus basal insulin, if
the current consensus recommendations have been developed
blood glucose control remains inadequate.44
which are summarized in Table 2.
INCG guidelines recommend titration of premixed insulin
therapy from OD to BID, if HbA1c > 8.5%.27 Similarly, if a patient
on premixed insulin (OD or BID) has within-target pre-meal
Proposed Algorithm for Initiation and
blood glucose but HbA1c > 7%, intensification of premixed Intensification of Insulin Therapy in
insulin to BID or TID should be considered.45 When the total
daily dose of insulin in an OD regimen exceeds 20 U, the regimen
Patients with Type 2 Diabetes Mellitus
should be intensified to BID such that the dose is distributed as Based on the consensus guidelines developed for initiation
two third in morning and one third in evening. However when and intensification of insulin therapy in patients with type 2
the single dose exceeds 30 units, the dose can be split into two diabetes mellitus, an algorithm has been proposed (Figure 3).
equal doses, which reduces the chance of hypoglycaemia. The 45

current consensus recommendations are in line with INCG Acknowledgements

guidelines.
Recommendations
When intensifying premixed insulin therapy from OD to
BID, it is recommended to split the OD dose into equal
pre breakfast and pre dinner doses when total insulin
dose crosses 30 units (50:50) and doses titrated as per the
The authors thank Jeevan Scientific Technology Limited,
Hyderabad, India, for writing assistance in the development of
this manuscript.
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