CONSENSUS

Practical guidance on intensification of insulin therapy

with BIAsp 30: a consensus statement
A. G. Unnikrishnan,1 J. Tibaldi,2 M. Hadley-Brown,3 A. J. Krentz,4 R. Ligthelm,5 T. Damci,6
J. Gumprecht,7 L. Ger}
o,8 Y. Mu,9 I. Raz10

1
Department of Endocrinology
SUMMARY
What’s known and Diabetes, Amrita Institute
Background: Basal insulin and premix insulin are commonly prescribed first-line Intensification of failing insulin therapy can be of Medical Sciences, Kochi,
India
insulin therapies for patients failing to maintain glycaemic control on oral therapy. achieved with BIAsp 30, dosed up to three-times- 2
Queens Diabetes &
When control on these insulins starts to drift, premix analogues, such as biphasic daily. At present, international recommendations for
Endocrinology, Fresh Meadows,
insulin intensification using premix analogues are
insulin aspart 30 ⁄ 70 (BIAsp 30), are a simple and effective tool for intensification NY, USA
limited and specific guidance on dosing is not 3
The Surgery, Thetford, Norfolk
as they can be injected up to three-times daily (TID). However, at present, interna-
available for many scenarios. In October 2008, an Primary Care Trust, Norfolk, UK
tional recommendations for intensification of insulin therapy using premix ana- international, independent, expert panel met to 4
Department of Diabetes,
logues are limited and specific guidance on dosing is not available for many review the current guidelines for insulin Southampton General Hospital,
scenarios. Methods: In October 2008, an international expert panel met to review intensification therapy with BIAsp 30 with the aim Southampton University
the current guidelines for insulin intensification with BIAsp 30 in patients with type of developing international practical guidance for Hospitals NHS Trust,
Southampton, UK
2 diabetes, with the aim of developing practical guidance for general and specialist general and specialist practitioners. 5
EHM Clinic, Hoofddorp, The
practitioners. Results: Simple treatment algorithms have been developed for (i) What’s new Netherlands
6
patients on basal insulin (human or analogue) once daily or twice daily (BID) who Treatment algorithms are presented to help
Division of Endocrinology,
need intensification to BIAsp 30 BID, and (ii) patients on BIAsp 30 once daily or Diabetes and Metabolism,
physicians intensify insulin therapy in patients with
Istanbul University Cerrahpasa
BID who can be intensified to BIAsp 30 BID or TID. As well as these algorithms, type 2 diabetes: from basal insulin OD or BID to Medical Faculty, Istanbul,
specific guidance has been provided on dose transfer (from basal insulin to BIAsp BIAsp 30 BID, and from BIAsp 30 OD and BID to Turkey
30), dose split (when intensifying from once daily to BID), and combination oral BIAsp 30 BID and TID, respectively. Randomised 7
Department and Clinic of
therapies. In addition, a guide to dose titration is included. Conclusions: The controlled trials and observational studies available Internal Medicine, Diabetology
on PubMed, involving insulin therapy being and Nephrology, Silesian
guidelines presented here should enable general or specialist practitioners to use University of Medicine,
intensified with BIAsp 30, were reviewed to help
BIAsp 30 to intensify the insulin therapy of patients failing on basal insulin or provide guidance on injection frequency, dose Katowice, Poland
8
BIAsp 30 once or twice daily. transfer and titration.
First Department of Internal
Medicine, Semmelweis
University, Budapest, Hungary
9
Department of Endocrinology,
PLA General Hospital, Beijing,
two commonly prescribed first-line insulin therapies China
Introduction 10
(7). Internal Medicine, Hadassah
Hospital, Jerusalem, Israel
Type 2 diabetes has reached pandemic proportions Although basal insulin, in combination with oral
across the world and the problem continues to grow antidiabetics (OADs), is an effective first insulin ther- Correspondence to:
(1,2). Type 2 diabetes is a progressive disease, char- apy for patients with poorly controlled type 2 diabetes A. G. Unnikrishnan, Department
of Endocrinology and Diabetes,
acterised by diminishing b-cell function in the con- (8), its efficacy eventually reaches a limit in some
Amrita Institute of Medical
text of insulin resistance, driven by obesity (3–5). patients because, while fasting blood glucose may be Sciences, Kochi, Kerala 682
Impaired glucose tolerance precedes type 2 diabetes at target, postprandial hyperglycaemia may continue 026, India
Tel.: + 91 484 2205343
and, by the time of clinical diagnosis, patients have to rise and contribute to overall glycaemic levels (9).
Fax: + 91 484 2802020
lost about half of their b-cell insulin-producing In the large, international, PRESENT observational Email:
capacity (3,6). study, the average baseline HbA1c in patients receiving [email protected]
Therapy for type 2 diabetes needs to be steadily basal insulin (analogue or human) was greater than
Disclosure
intensified in line with the disease progression. Once 9.3% (10), possibly at least in part because of impair- The meeting on which this
insulin therapy has been initiated – following the ment of the second phase insulin release resulting consensus statement is based
was funded by a grant from
failure of lifestyle changes and oral therapy to keep from b-cell glucotoxicity as diabetes progresses (4).
Novo Nordisk A/S, Denmark,
patients in glycaemic control – there is often a need Intensified insulin therapy, which includes a rapid- and all authors have received
for intensification from basal insulin or a once-daily acting prandial component, is therefore appropriate consultancy honoraria from
Novo Nordisk and other
(OD) regimen of premix insulin (comprising both for these patients. Similarly, patients who are failing to
pharmaceutical companies.
basal and prandial insulin components), as these are maintain glycaemic control on OD analogue premix

ª 2009 Blackwell Publishing Ltd Int J Clin Pract, November 2009, 63, 11, 1571–1577
doi: 10.1111/j.1742-1241.2009.02192.x 1571
1572 Consensus statement on intensification with BIAsp 30

need intensification to twice daily (BID) to address the (intensifying to TID as required) as a treatment
postprandial glucose (PPG) excursions after more than option for patients with type 2 diabetes switching
one meal per day (11,12). In the 1-2-3 study by Garber from basal insulin (19). The initial dose was recom-
et al., 41% of patients with type 2 diabetes who were mended to be 80% of the final basal dose with titra-
prescribed the analogue premix, biphasic insulin aspart tion to target over 14 days. However, these
30 ⁄ 70 (BIAsp 30, comprising 30% prandial insulin guidelines fail to include guidance on how the dose
aspart and 70% basal protaminated aspart), achieved should be split and titrated (19). New international
HbA1c < 7.0% on an OD regimen over 16 weeks. guidelines that cover all appropriate scenarios for
However, when the BIAsp 30 regimen was intensified insulin intensification with premixed analogues are
to BID and three-times daily (TID) (as necessary), 70% therefore needed.
and 77% of patients, respectively, were able to reach As the diabetes pandemic grows, primary care
this glycaemic goal (12). physicians will need to treat an increasing number of
International data from routine clinical practice patients with type 2 diabetes because there will be
show that glycaemic control in patients with type 2 too many cases for specialists to deal with (20).
diabetes is poor on average, even in patients using Guidelines for insulin intensification therefore need
insulin: almost 50% of patients in the IMPROVE to be straightforward, comprehensive and easily
observational study had HbA1c ‡ 9.0% at the base- implemented.
line visit (13). Improving treatment and disease man- BIAsp 30 is the most prescribed analogue premix
agement in type 2 diabetes is therefore crucial if and consequently has the largest evidence base in
long-term vascular complications are to be mini- terms of randomised controlled trials (RCTs) and
mised (14–16), and intensification of failing insulin observational data. It follows that BIAsp 30 is there-
therapy is a key step in this process. fore the analogue premix most likely to be used for
At present, international recommendations for insulin intensification, both from basal insulin and
intensification of insulin therapy using premix ana- from BIAsp 30 regimens: OD to BID and from BID
logues are limited. The American Association of to TID. In October 2008, an independent interna-
Clinical Endocrinologists’ (AACE) guidelines (17) tional expert panel – comprising the authors o7f this
cover the following: report – met to review the current guidelines for
insulin intensification therapy using BIAsp 30 in
• Transition from a long-acting insulin analogue to
patients with type 2 diabetes, with the aim of devel-
a premixed insulin analogue BID.
oping international practical guidance for general
• Transition from a OD premixed insulin analogue
and specialist practitioners.
to a BID premixed insulin analogue.
In both scenarios, the recommendations are as fol-
Which patients need intensified
lows: (following 1 : 1 dose transfer from basal insu-
therapy? Clinical evidence for
lin) divide the total daily dose into two equal doses;
intensification with BIAsp 30
give half before breakfast, the other half before din-
ner; titrate to goal based on self-monitored blood Patients who need intensified insulin therapy can
glucose data and diet history; the largest meal will essentially be grouped into two categories: those who
require a larger proportion of insulin; reduce the started insulin with basal therapy and can no longer
total dose by 20% if the patient experiences recurrent maintain glycaemic control, and those using BIAsp
hypoglycaemia. 30 OD or BID and failing to maintain adequate gly-
The AACE guidelines (17) thus do not cover the caemic control.
possible intensification from BID premix analogue to
TID premix analogue. The International Diabetes
Patients failing on basal insulin
Federation (IDF) guidelines (18) mention premixes
as viable intensification options but offer no specific Initiating insulin therapy with a basal insulin ana-
guidance. logue in patients failing on OAD therapy can be
The BIAsp 301 EU label has the indication for pro- effective (21,22), but intensification may be needed
gressing from OD to BID and from BID to TID, but long-term. Few studies have addressed the question
again no specific dosing guidelines are given for of what happens to glycaemic control in patients
intensification. A recent consensus statement from with type 2 diabetes failing to maintain glycaemic
the UK recommended premix analogues BID goals on basal insulin, after a switch to BIAsp 30.
One RCT, the PREFER study, randomised 719
patients previously treated with two OADs with, or
1
Novo Nordisk A ⁄ S, Bagsværd, Denmark. without, basal insulin to either BIAsp 30 BID or

ª 2009 Blackwell Publishing Ltd Int J Clin Pract, November 2009, 63, 11, 1571–1577
 Consensus statement on intensification with BIAsp 30 1573

basal–bolus therapy (insulin detemir and insulin regimen, regardless of prior basal insulin injection
aspart) (23). After 26 weeks of therapy, patients pre- frequency. The dose increase over the observation
viously treated with basal insulin showed a reduction period was similar in both groups (0.14 vs.
in HbA1c of 0.75% (baseline level for the BIAsp 30 0.13 U ⁄ kg) (24).
group was 8.40%). Although previous basal insulin To summarise, when BIAsp 30 BID was started
dose was not reported, the total daily BIAsp 30 dose following basal insulin therapy in routine care, the
increased by 0.16 U ⁄ kg (from 0.47 to 0.63 U ⁄ kg) dose was transferred either 1 : 1 (if human basal)
from week 3 to week 26, with a 50 ⁄ 50 breakfast ⁄ din- or 1 : 1.3 (if analogue basal), without any safety
ner dose split (23). concerns and resulted in improved glycaemic
Other evidence comes from large observational control. When switching from OD basal insulin, the
studies: PRESENT and IMPROVE. These interna- starting BIAsp 30 dose was smaller than when
tional, non-interventional studies have reported on switching from BID basal insulin, giving an average
the effectiveness and safety profile of BIAsp 30 in dose transfer of 1 : 1.2. In addition, data from
routine care in patients from a variety of prestudy RCTs have shown that BID BIAsp 30 administra-
therapies, including basal insulin. In the PRESENT tion resulted in a 50 : 50 breakfast ⁄ dinner dose
analysis, glycaemic control at baseline was poor in distribution.
this patient group, with HbA1c > 9.3% for those
previously treated with human or analogue basal
Patients failing on OD or BID BIAsp 30
insulin (10). After 6 months of BIAsp 30 therapy,
HbA1c decreased by a mean of 1.42% and 1.60%, Initiating insulin therapy with BIAsp 30 OD is also a
respectively. In terms of dosing, prestudy basal successful strategy for improving glycaemic control in
insulin doses were 0.46 for human and 0.34 U ⁄ kg patients with type 2 diabetes failing on oral therapy
for analogue. When the switch to BIAsp 30 was (11,25–27). However, as demonstrated in the 1-2-3
made, doses were transferred, on average, approxi- study (12), BIAsp 30 OD will generally only get a
mately 1 : 1 for those coming from human basal minority of patients to the HbA1c target of < 7.0%,
(mean total baseline BIAsp 30 dose: 0.50 U ⁄ kg) and but the proportion is increased when dosing is inten-
1 : 1.3 for those coming from analogue basal (mean sified to BID and, if necessary, TID. In this study,
total baseline BIAsp 30 dose: 0.45 U ⁄ kg). During 100 patients with type 2 diabetes, previously treated
the 6-month observation period, doses underwent with OADs (with or without basal insulin), were ini-
very little titration: final doses were 0.56 and tiated with, or switched basal insulin therapy to,
0.48 U ⁄ kg, respectively (10). The increase in dose BIAsp 30 OD for 16 weeks. After this time, 21% of
when patients transferred from analogue basal insu- patients reached the IDF (18) HbA1c target of
lin to BIAsp 30 did not, however, have corollaries < 6.5% and left the study. The remaining patients
in terms of hypoglycaemia; the rates of major and were intensified to BIAsp 30 BID and, after 16 weeks,
minor hypoglycaemia were reduced following BIAsp to TID if this target had not been reached. This
30 therapy compared with rates on analogue basal intensification strategy enabled 41%, 70% and 77%
insulin (major: 1.1–0.03, p < 0.05; minor: 2.9–2.2 of patients on OD, BID and TID to reach HbA1c
episodes ⁄ patient ⁄ year, not statistically significant, < 7.0%, respectively (12). The daily insulin dose
p > 0.05) (10). for patients who achieved the target HbA1c of
In the largest observational study to date of BIAsp £ 6.5% on BIAsp 30 OD was 0.60 U ⁄ kg. For patients
30 in routine care, IMPROVE, patients who were who finished the study on BIAsp 30 BID, the total
switched from basal insulin to BIAsp 30 were, again, dose almost doubled (due to the extra injection
in poor glycaemic control. Mean HbA1c was over and the relatively aggressive titration algorithm
9.0% and patients had been diagnosed with type 2 used in this study), with a mean dose split close
diabetes, on average, more than 11 years previously to 50 ⁄ 50 (0.51 ⁄ 0.64 U ⁄ kg breakfast ⁄ dinner). For
(24). After 26 weeks of BIAsp 30 therapy, reductions those who finished on BIAsp 30 TID, the dose split
in HbA1c were )1.64% in patients previously on was 38 ⁄ 16 ⁄ 46% breakfast ⁄ lunch ⁄ dinner (0.58 ⁄ 0.25 ⁄
human basal insulin, and )1.83% in those previously 0.70 U ⁄ kg respectively).
on analogue basal insulin. When switching to Even when the total daily dose with BIAsp 30 TID
BIAsp 30, the transfer of dose was 1 : 1.2 on average was smaller (0.59 U ⁄ kg), as in the REFORM study
(0.33–0.40 U ⁄ kg), but patients previously on OD (27), the breakfast ⁄ lunch ⁄ dinner dose split was
basal insulin were started on a lower BIAsp 30 virtually the same: 34 ⁄ 17 ⁄ 49% (0.20 ⁄ 0.10 ⁄ 0.29 U ⁄ kg,
dose than those previously on BID basal insulin respectively). In this study, 101 patients inadequately
(0.36 and 0.44 U ⁄ kg, respectively). The majority of controlled on OAD combination therapy were rando-
patients (82%) were transferred to a BID BIAsp 30 mised to repaglinide 6 mg ⁄ day or metformin 2 g ⁄ day

ª 2009 Blackwell Publishing Ltd Int J Clin Pract, November 2009, 63, 11, 1571–1577
1574 Consensus statement on intensification with BIAsp 30

in combination with BIAsp 30 OD (6 U). If targets international expert panel agreed on the following
were not met [fasting plasma glucose (FPG) 4.0– guideline for the intensification of insulin therapy
6.0 mmol ⁄ l, HbA1c < 6.5%], patients were intensified using BIAsp 30.
to BIAsp 30 BID and then TID at 3, 6 or 9 months.
After 12 months, 42% of patients were receiving BIAsp
Practical guidelines for insulin
30 TID. Their mean HbA1c was 7.0%, and 26% of
intensification with BIAsp 30
patients achieved HbA1c < 6.5% (27).
The observed doubling of the BIAsp 30 dose when Switching from basal insulin OD or BID to
intensifying from OD to BID in the 1-2-3 study (12) BIAsp 30 BID
was also seen in the trial by Bebakar et al. (11). Here, A simple algorithm for switching patients from OD
191 patients with type 2 diabetes, previously insulin- or BID basal insulin (analogue or human) to BIAsp
naı̈ve, were randomised 2 : 1 to BIAsp 30 OD or to an 30 BID is shown in Figure 1. Regardless of basal reg-
optimised OAD regimen. After 13 weeks, HbA1c was imen, if a patient has HbA1c higher than 8.0%, they
reduced by a significantly greater amount with BIAsp should be transferred to BIAsp 30 BID. If HbA1c is
30 OD than with optimised OADs ()1.16% vs. moderately elevated (between 7.0% and 8.0%) but
)0.58%, p < 0.001), but only 25% of patients on FPG is within the normal range (4–6 mmol ⁄ l), the
BIAsp 30 OD reached HbA1c < 7.0%. Those patients suboptimal overall glycaemia is probably caused by
with HbA1c > 8.5% or FPG > 7 mmol ⁄ l at this point elevated PPG, thus the patient should be transferred
were intensified to BIAsp 30 BID for a further to BIAsp 30 BID as it provides prandial coverage as
13 weeks. At the end of the study, HbA1c was reduced well. If, however, HbA1c is between 7.0% and 8.0%,
by )1.34% in those on BIAsp 30 BID and by )1.24% and FPG is higher than 6 mmol ⁄ l, the existing basal
in those who had remained on BIAsp 30 OD. The insulin dose(s) can be titrated further until the
starting insulin doses for those who finished on BIAsp patient achieves FPG below 6 mmol ⁄ l. If recurrent
30 OD or BID were very similar: 0.17 and 0.16 U ⁄ kg, hypoglycaemia limits uptitration of the basal dose, or
but patients who intensified to a BID regimen finished the daily dose reaches 0.5 U ⁄ kg (insulin units per kg
the 26-week trial with a BIAsp 30 dose approximately body weight), switching to BIAsp 30 BID can be
double that of those who remained on an OD regimen: considered.
0.22 vs. 0.43 U ⁄ kg (11). When switching a patient from basal insulin OD
To summarise, in treat-to-target intensification or BID to BIAsp 30 BID, the points in Box 1 provide
studies, the total dose of BIAsp 30 increased consid- some practical guidance.
erably following the consecutive intensification from
OD to BID to TID. The dose distribution of BID Intensification with BIAsp 30: from OD to BID
BIAsp 30 administration was close to 50 : 50, while and from BID to TID
in studies where patients had intensified to a TID An algorithm for intensifying therapy from BIAsp
regimen, the highest dose of BIAsp 30 was given at 30 OD or BID to BIAsp 30 BID or TID is shown in
dinner, followed by the doses at breakfast and lunch. Figure 2. If a patient receiving BIAsp 30 OD or BID
On the basis of an assessment of the published data, has FPG (with or without predinner blood glucose
combined with many years of clinical experience, the measurement) within the normal range (4–6 mmol ⁄ l),

Basal insulin OD or BID

HbA1c7–8% HbA1c> 8.0%

FPG > 6 mmol/l FPG: 4–6 mmol/l

(FPG >110 mg/dl) (FPG: 73–110 mg/dl)

Titrate basal insulin to

achieve Switch to BIAsp 30 BID
FPG < 6 mmol/l
(FPG < 110 mg/dl)

Figure 1 A simple algorithm for the intensification of basal insulin therapy once daily (OD) or twice daily (BID)
(analogue or human) to biphasic insulin aspart 30 ⁄ 70 (BIAsp 30) BID. FPG, fasting plasma glucose

ª 2009 Blackwell Publishing Ltd Int J Clin Pract, November 2009, 63, 11, 1571–1577
 Consensus statement on intensification with BIAsp 30 1575

BIAsp 30 OD (pre dinner) or BIAsp 30 BID

FPG and/or pre dinner BG: 4–6 mmol/l FPG and/or pre dinner BG > 6 mmol/l
(73–110 mg/dl) (110mg/dl)

HbA1c > 7.0% Titrate BIAsp 30 OD or BID to achieve

FPG and/or pre dinner BG < 6 mmol/l
(110 mg/dl)

If hypoglycaemia
occurs

Switch to BIAsp 30 BID or TID

Figure 2 A simple algorithm for intensifying therapy from biphasic insulin aspart 30 ⁄ 70 (BIAsp 30) once (OD) or twice
daily (BID) to BIAsp 30 twice or three-times daily (TID). FPG, fasting plasma glucose; BG, blood glucose

online at: http://www.emea.europa.eu/humandocs/

Box 1 Practical guidance for switching from basal
insulin OD or BID to BIAsp 30 BID
PDFs/EPAR/Novomix/H-308-PI-en.pdf)

1 : 1 Total dose transfer to BIAsp 30

Split the dose 50 : 50 prebreakfast and predinner Box 2 Practical guidance for switching from BIAsp 30
Titrate the dose preferably once a week OD to BID
Discontinue sulfonylureas (SUs)
Split the OD dose into equal breakfast and dinner doses
Continue metformin
(50 : 50)
Consider discontinuing thiazolidinediones (TZDs) as per local
Titrate the doses preferably once a week according to the
guidelines and practice
algorithm below
Administer BIAsp 30 just before meals
Discontinue SUs
Continue metformin
but has HbA1c higher than 7.0%, the suboptimal Consider discontinuing TZDs as per local guidelines and
overall glycaemia is probably caused by elevated PPG practice
after a meal not covered by BIAsp 30, thus they should Administer BIAsp 30 just before meals
be transferred to BIAsp 30 BID or TID (i.e., the
addition of just one daily injection). If, however, FPG
(with or without predinner blood glucose measure- Box 3 Practical guidance for switching from BIAsp 30
ment) is higher than 6 mmol ⁄ l, the existing BIAsp 30 BID to TID
dose(s) (OD or BID) should be titrated until the
patient achieves FPG below 6 mmol ⁄ l. If while doing Add 2–6 U or 10% of total daily BIAsp 30 dose before lunch
so hypoglycaemia2 occurs, the patient should be Down-titration of morning dose ()2 to 4 U) may be needed
after adding the lunch dose
intensified to BIAsp 30 BID or TID (i.e., the addition
Titrate the doses preferably once a week according to the
of just one daily injection).
algorithm below
When intensifying a patient’s therapy from BIAsp
Continue metformin
30 OD or BID to BIAsp 30 BID or TID, the points in Consider discontinuing TZDs as per local guidelines and
Boxes 2 and 3 provide some practical guidance. practice
Administer BIAsp 30 just before meals
Titration algorithm for implementing the
above guidelines
This algorithm is taken from the INITIATE study
(28) and the current NovoMix 30 EU label (available Preprandial blood glucose value Dose change

< 4.4 mmol ⁄ l < 80 mg ⁄ dl )2 U

2
Hypoglycaemia is defined by the United Kingdom Pro- 4.4–6.1 mmol ⁄ l 80–110 mg ⁄ dl 0
spective Diabetes Study as a minor event if the patient is able 6.2–7.8 mmol ⁄ l 111–140 mg ⁄ dl +2 U
to self-treat the symptoms, unaided, and a major event if 7.9–10.0 mmol ⁄ l 141–180 mg ⁄ dl +4 U
third-party help is required or it necessitates medical inter- > 10.0 mmol ⁄ l > 180 mg ⁄ dl +6 U
vention (14).

ª 2009 Blackwell Publishing Ltd Int J Clin Pract, November 2009, 63, 11, 1571–1577
1576 Consensus statement on intensification with BIAsp 30

When using this titration algorithm to adjust • Multiple doses of insulin are easier to administer
BIAsp 30 doses after intensifying basal insulin ther- using injection pen-type devices (30).
apy to BIAsp 30 BID, or intensifying BIAsp 30 OD • When the daily insulin dose in a OD regimen
or BID to BIAsp 30 BID or TID, the following guid- nears 40–50 U, intensifying the regimen to BID is a
ance should be noted: safer way to proceed than simply increasing the dose
further, as the dose can be split into two equal doses,
• The lowest of three previous days’ premeal levels
which reduces the chance of hypoglycaemia. Each of
should be used.
these doses can then be titrated.
• Always change the meal-time dose preceding the
• For patients receiving BIAsp 30 TID, data from
measurement.
RCTs indicate that the dose distribution should
• The dose should not be increased if hypoglycaemia
approximate the ratio 2 : 1 : 3, breakfast:lunch:din-
occurs during these days.
ner (or 33 ⁄ 17 ⁄ 50%).
• Dose adjustments can be made once a week until
• BIAsp 30 TID may be a useful alternative to basal–
target is reached.
bolus therapy for some patients, as fewer daily injec-
• Only one dose at a time should be changed: the
tions are required and only one insulin and one
evening dose should be titrated first, followed by the
device need be used, eliminating the potential for
breakfast dose and finally the lunch dose as appro-
mixing up insulins and hence incorrect dosing.
priate.
• Weight gain is a potential barrier to insulin ther-
apy in patients with type 2 diabetes; patients need to
have realistic expectations and manage potential
Considerations for dosing and
weight gain with a regimen of healthy diet and exer-
titration of BIAsp 30
cise. Continuing metformin therapy might help min-
When to down-titrate imise unwanted weight gain (31).
Down-titrate the dose if major or recurrent minor
hypoglycaemia occurs (the United Kingdom Prospec-
tive Diabetes Study defined minor hypoglycaemic Acknowledgements
events as those for which the patient was able to
The meeting on which this consensus statement is
self-treat the symptoms, unaided, while major hypo-
based was funded by an independent grant from
glycaemic events were those that required third-party
Novo Nordisk A ⁄ S, Denmark and all authors have
help or necessitated medical intervention) (14).
received consultancy honoraria from Novo Nordisk
and other pharmaceutical companies. Editorial assis-
Patient demographics
tance was provided by Watermeadow Medical Plc,
• Guidance is aimed at the typical patient with type Witney, UK, sponsored by Novo Nordisk.
2 diabetes.
• These guidelines assume no metabolic decompen-
Author contributions
sation (diabetic ketoacidosis, extreme hyperglyca-
emia, fluctuating glucose levels). All authors contributed to the discussion and prepa-
• These guidelines may not be applicable in special ration of the consensus algorithms and critically
situations like pregnancy, acute coronary events, revised and approved the manuscript.
patients treated in intensive care units, sepsis and
any other critical illnesses.
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