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© SUPPLEMENT TO JAPI • april 2011 • VOL. 59

Insulin Pens: The Modern Delivery Devices

Manash P Baruah

Abstract
Strict glycemic control helps in reducing complications and mortality in patients with diabetes. Insulin remains the
mainstay in treatment of diabetes. One of the most important barriers to insulin therapy is the use of conventional insulin
delivery system, which remains time-consuming, cumbersome, inconvenient and painful. Insulin dosing via syringe is
associated with a high risk of dosage errors. The modern pen devices have various advantages over the conventional
insulin delivery methods. The user-friendliness and comfort of injection makes the initiation of insulin easier. The ease
of use of insulin pens and the flexibility of incorporating insulin injections into a busy lifestyle may improve diabetes
control with much less effort, while maintaining the quality of life for the diabetic patients. Reusable and prefilled pens
are available.

Introduction and Rationale for the Use counterparts (Table 1).3 Insulin pens have become extremely
popular throughout the world; in some countries, 70% to 90%
of Insulin Pens of all insulin is delivered by pen devices.4 Insulin pen devices

T he beneficial role of strict glycemic control in people with
diabetes has been proven in many large clinical studies and
the evidence is getting stronger.1 There has been a tremendous
improvement in the number of patients achieving the target
glycemic control. This has been made possible as the result
of advances in medical science since the discovery of insulin
by Banting and Best in 1921. Insulin has been the mainstay of
therapy for all subjects with type 1 diabetes and majority of type
2 diabetic subjects. However, there are several barriers to insulin
therapy that need to be addressed. One of the most important
barrier is the use of conventional insulin delivery process, which
remains time-consuming, cumbersome, inconvenient, and to
some extent, painful. Furthermore, insulin dosing via syringe is
associated with a high risk of dosage errors, with as many as 80%
of patients carrying out some aspect of insulin administration
via syringe incorrectly.2
Although insulin was discovered almost 9 decades ago, the
technology involving the insulin delivery did not see much of
change till the introduction of pen device in 1985. The provisions
for insulin delivery have come a long way from very crude and
inconvenient metal syringes to the modern pen devices with
very fine needles for accurate, flexible, convenient, and virtually
painless administration. Insulin pens have the potential to
become a major asset for breaking barriers to early initiation of
insulin as they overcome many shortcomings of their previous
Table 1: Advantages of insulin pen devices over
conventional insulin syringes
More discreet
More convenient insulin delivery
More accurate dosing
Less pain because smaller-gauge needles are used
Better quality of life
Easier compliance with insulin regimen
Simpler for specific populations to use (e.g., older adults, children
and adolescents, and pregnant women)
Improved social acceptability, especially at school or other social
gatherings
More flexibility because of disposable or reusable options
Consultant Endocrinologist, Excel Care Hospitals, Maya-Ville,
Borthakur Mill Road, Ulubari, Guwahati, Assam, 78100, India
are unique in that they combine the insulin container and the
syringe in a single unit. Some of these pen devices feature an
audible click on dose dialing, single-unit dose increments,
two-way dose setting, large dials showing the selected dose, and
automatic return to zero after dialing the full dose.4 With these
state-of-the-art insulin pens, physicians will also find that their
efforts are more rewarded, which may hold the key to better
long-term outcomes.
Types of Insulin Pens
The 2 types of insulin pens available currently are reusable
and prefilled (disposable) pens.
Reusable pens: In reusable pens, an insulin cartridge is
inserted into the pen’s delivery chamber. For patients, this
allows greater flexibility (i.e., changing types of insulin without
a need to buy another pen if prescription changes), and it may be
more economical than using prefilled pens. In addition to being
durable and easy to use, the reusable pens are designed for longer
duration of use. With individual use of the pen device, the risk
of infection is minimized.5 Examples of such reusable(durable)
pens are NovoPen® 3 (for both human and analog insulins),
Humapen® (for both human and analog insulins), Optipen®,
Autopen® pen, and Wosulin pen. HumaPen® MEMOIR(TM) comes
with a “memory” allowing patients, especially those on multiple
mealtime doses, to record and review their last 16 insulin doses,
including the priming doses. NovoPen® 4, which is yet to be
launched in India, has shown dose accuracy before and after
simulation of 5 years of use across a wide range of temperature
and humidity conditions and after mechanical challenges.
The mean injection force required to operate NovoPen® 4 was
reduced up to 50% as compared to that for NovoPen® 3, and the
mean dosage display for NovoPen® 4 was over 4 times larger
than that for NovoPen® 3. Based on these findings, patients
with diabetes who have manual or visual impairment should
find it easier to dose insulin with NovoPen® 4. NovoPen® junior
and HumaPen®luxura(TM) HD are 2 innovation designed mainly
for young children with diabetes to facilitate dialing at small
quantum such as 0.5­–1 IU. A large body of published evidence
accumulated over the past 2 decades testifies to the patient-
related benefits of the NovoPen family of insulin injection devices
in the treatment of diabetes. The insulin cartridges fitting durable
pens are called penfills. Insulin cartridges for the reusable pens are
generally available in 3.0-ml volume (300 units) and are specific
© SUPPLEMENT TO JAPI • april 2011 • VOL. 59 39
Table2. Comparison of acceptability of injection device vs.
conventional syringes by elderly diabetic
Outcome of Favors pen Favors syringe Favors none
questionnaire device (%) device (%) (%)
Easy and quick 88 12 00
operability
Pain experienced during 62 02 43
injection
Easy pre-selection of 86 14 00
insulin dose
Overall acceptability 90 02 08
for the pen size. The penfills should be stored in the refrigerator
before use. However, once a cartridge is placed in a reusable
pen, the pen can be kept at room temperature for a month, as
long as it is kept away from direct heat and light.
Prefilled pens: Prefilled pens contain a built-in single-use
insulin cartridge. Because this device requires no loading by the
patient, it is very convenient and easy to use. These portable,
durable, and lightweight delivery systems are particularly
helpful for patients who have difficulty handling the cartridges
in reusable pens or people with busy schedules who prefer not to
change cartridges. The examples of reusable pens are NovoLet®,
Humaject®, KwikPen®, Optiset®, and SoloSTAR®. The newest of
the prefilled pens available for both human and analog insulins
is the Next Generation FlexPen® from Novo-Nordisk which has
single-unit dosing increments, audible clicks when dialing the
dose, a large magnifying window that shows the unit dose,
two-way dose setting that allows the user to decrease the dose
without taking the pen apart or discharging insulin from the pen,
and an end-of-dose click that indicates that the full dose has been
delivered. Currently, it has become the most popular prefilled
pen device being used by millions worldwide.6,7
The Next Generation FlexPen®, which has been available
in some countries from the late 2008 and is continuing to be
launched in countries around the world (including India),
has been built upon the high standards set by the FlexPen®.
Emphasis has been given towards new features like less injection
force easily noticeable labels and packaging to aid insulin
type identification and an innovative simple and easy needle
attachment with a “just twist” mechanism.8-10 These features
provide improved convenience and ease of use for people with
diabetes. 4,5
Advantages of Insulin Pen Devices:
Clinical Evidence
Insulin pens vs vials and syringes
Several clinical studies have evaluated the use of insulin pens
since their introduction in 1985. The first clinical study reported
that the pen’s advantages outweigh the inconvenience of multiple
injections.11 The findings from a study on elderly diabetics
favored pen devices over syringes in terms of operability, pain,
insulin dose pre selection and overall acceptability (Table 2).2
In a study 74% patients preferred FlexPen® as compared to
20% preferring vials and syringes citing the following as the
main reasons for the preference : (i) more discreet to use in
public, (ii) ease of reading dose scale and use.12 Many studies
have also shown better convenience, flexibility, and quality of
life results with pen devices as compared to the conventional
insulin delivery devices.6 Dose accuracy with insulin pens was
also reported to be better in many studies in comparison to vials
and syringes method especially at low doses (≤5 IU).7,13,14 All
Next Generation FlexPen® is more accurate
than SoloSTAR® - at a dose of 30 U
Test if dose accuracy is within limits based on ISO standards
(±1.5 U), when pens are used according to user manual
Next Generation FlexPen® underdosed one dose, whereas SoloSTAR®
underdosed three doses
Fig. 1. Comparison of Next Generation FlexPen® vs. SoloSTAR®
(source: ref 8)
these factors are important in improving the patient adherence
to the treatment and also reducing the hypoglycemic episodes.15
Comparative Evidence between
Available Pen Devices
It is pertinent to recall the definitions of the following terms
before interpreting the findings of various studies comparing
the efficacy an accuracy of different insulin delivery devices.
Injection force: It is the peak force attained when pushing
the dose knob of a pen device during injection. As injection force
increases, the user would need to exert proportionately greater
effort in self administering a prescribed dose.16
Glide force variability: It is the variation of force during
steady-state dosing. It is used to quantify “smoothness” of
injection as a means of translating a technical measure into
clinical application.17
Dose accuracy: It is tested in vitro by measuring the delivered
doses under reference conditions, such as temperature and
relative humidity, on a highly sensitive balance and is corrected
for the specific density of the insulin used (according to
specification of International organization for standardization
(ISO) 11608-1. The precision is calculated from the variance
around the mean delivered dose.9
Transition from conventional delivery device to NovoPen®
has been found to be associated with more accurate dosing, while
the glycemic control was equivalent, and in some cases superior,
without increase in the hypoglycemia incidences.17 Confidence
in patients’ ability to use the device was reported better with
FlexPen® as compared to Humulin® Pen and Optiset® by both
patients and physicians.18 In comparative studies, patients
experienced fewer problems and preferred FlexPen® than
Humalog Pen.19 When these pens were compared with respect
to dosing error, Humalog pen delivered underdoses in 17.1%
and 28.9% at both the 10 IU and 30 IU doses respectively,
whereas FlexPen® delivered all doses within prespecified limits.14
Similarly, dose accuracy was found to be more with FlexPen®
with superior glycemic control and without increase in the
hypoglycemia incidences.20
In a direct head-to-head comparison of the 2 prefilled insulin
pens, Next Generation FlexPen® and SoloSTAR® at a dose of 10
U and 30 U with a standardized protocol, the Next Generation
FlexPen® was found to be more accurate than the SoloStar®
40 © SUPPLEMENT TO JAPI • april 2011 • VOL. 59
Fig 2. Comparison of 3 commonly used prefilled insulin pens
(source: ref 21)
at both tested doses. Only 0.2% of the doses were outside the
ISO limit at 10 IU with the NG FlexPen (0.6% at 30 IU). The
corresponding figures for the SoloStar® were 0.4% and 1.8%,
respectively (Figure 1).8
Rissler et al. evaluated force dynamics of Next Generation
FlexPen® and SoloSTAR® at 3 different injection speeds (push-
button speeds: 4, 6, or 8 mm/s). They found that Next Generation
FlexPen® has a significantly lower (18 to 45%) injection force
at all speeds, and delivers 60 IU insulin faster (including
recommended waiting time) than SoloStar®.9 In yet another
study by Asakura et al.,21 Next Generation FlexPen® was found
to have a significantly lower (p < 0.05) mean injection force than
SoloStar® and KwikPen® when tested in vitro at ideal conditions
during injection of 20 IU insulin at 3 different speeds such as 3.3,
5, and 8.3 mm/s using either a BD Micro-Fine™ 31G thin-wall
needle or a NovoFine® 32G tip extra thin wall needle (Figure 2).
This is the only study comparing head to head the efficacy of 3
frontline modern pens recently introduced in the market.
A review article by Pfützner10 concluded that Next Generation
FlexPen is simple to use and is more accurate than other prefilled
pens. NGFP ensures a reduced injection force and allows easy
differentiation between insulin types.10
Insulin Pen Devices: Conclusion
The modern pen devices have various advantages over the
conventional insulin delivery methods. The user-friendliness
and comfort of injection makes the initiation of insulin, hitherto
considered a very difficult task, a lot easier. The ease of use of
insulin pens and the flexibility of incorporating insulin injections
into a busy lifestyle may improve diabetes control with much
less effort, while maintaining the quality of life for the diabetic
patients.
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