CLINICAL THERAPEUTICSVVOL. 20, NO.
3, 1998
Assessment by Patients with Diabetes Mellitus of Two
Insulin Pen Delivery Systems Versus a Vial and Syringe
Marilyn R. Graff, RN, CDE,’ and Mark A. McClunahan, MD2
‘Diabetes Care Team, Longmont Clinic, Longmont,
Thyroid Associates, Fredericksburg, Virginia
ABSTRACT
Two multicenter surveys were conducted
in a total of 13 10 insulin users over a
3-week period. The first survey, in which
803 patients participated, assessed the ef-
fects of using the Novolin Prefilled in-
sulin delivery system on lifestyle; com-
pliance with insulin, diet, and exercise
regimens; and feelings of well-being com-
pared with the traditional insulin vial and
syringe. The second survey, in which 507
patients participated, assessed attitudes
and perceptions of the NovoPen 1.5 in-
sulin delivery system compared with the
traditional insulin vial and syringe. Both
delivery systems are dial-a-dose insulin
pens containing a single-use NovoFine 30
insulin needle and are designed to be
portable and discreet. Patients using tbe
Novolin Prefilled delivery system com-
pleted a three-part questionnaire (two
parts at the initial survey visit and the
third at the end of 3 weeks); those using
the NovoPen 1.5 completed a question-
naire at the end of 3 weeks. Seven hun-
dred twenty-nine (92%) of 793 patients in
the Novolin Prefilled group and 482
486
Colorado, and 2Diabetes and
(98%) of 492 patients in the NovoPen 1.5
group reported that it was easy to use these
delivery systems; 672 (85%) of 791 pa-
tients reported that they missed no injec-
tions while using the Novolin Prefilled
system, compared with 566 (72%) of 789
patients using the vial and syringe. With
the NovoPen 1.5, 333 (73%) of 456 pa-
tients said that the dosing mechanism was
more accurate, and 351 (77%) of 456 pa-
tients found it easier to comply with their
insulin regimen. In both groups, patients
reported a strong desire to continue using
the insulin pens and a willingness to rec-
ommend their use to someone else. Be-
cause patients were more physically and
psychologically comfortable injecting in-
sulin with the Novolin Prefilled or
NovoPen 1.5 system than with an insulin
syringe, their overall attitude toward in-
sulin therapy improved, as did their con-
fidence about managing their disease. An
improved attitude toward insulin therapy
might be expected to lead to better accep-
tance of and compliance with an insulin
regimen. Key words: diabetes, insulin,
quality of life, compliance, insulin deliv-
ery systems, insulin pens.
0149-2918/98/$19.00
M.R. GRAFF AND M.A. McCLANAHAN
INTRODUCTION
Diabetes has an enormous impact on pa-
tients’ lives, requiring regular glucose
monitoring, modifications in diet and
lifestyle, frequent visits to physicians and
diabetes educators, daily administration
of medication, and, for many, self-inject-
ing with insulin. The health-care profes-
sional plays an important role in helping
patients achieve the best quality of life
possible, which means that professionals
and patients both must do more than fo-
cus on stabilizing blood glucose levels.
Equally important are education about di-
abetes and its treatment, active participa-
tion in instituting diet and lifestyle
changes, and fostering a positive attitude
about patients’ ability to comply with
medication regimens.’
A significant number of patients resist
taking insulin because of its inconve-
nience or imagined pain, the stigma of us-
ing a vial and syringe, or fear of self-
injection. 1-3 This may be especially true
for patients with type 2 diabetes, many of
whom had at one time been able to con-
trol their diabetes with diet and exercise,
oral medication, or both. These patients
may view the need for insulin as a sign
that their disease is worsening or that they
have failed to take care of themselves
properly.* Health professionals should be
aware of these feelings and be able to rec-
ommend appropriate self-care options for
the patient’s consideration.
The Novolin Prefilled@* system (a dis-
posable pen) and NovoPen@‘* 1.5 (a
durable pen with a replaceable cartridge)
*NovoPen@, Novolin R Prebilled”, Novolin N Pre-
filled”, Novolin 70/30 Prefilled”, NovoFine@,
Novolin@, and PenFilla are trademarks of Novo
Nordisk A/S, Copenhagen, Denmark.
are alternative insulin delivery systems
that allow patients to take insulin without
having to use a traditional insulin vial and
syringe. Each pen uses the NovoFine@‘*
30 insulin needle, which is disposed of af-
ter one injection. The NovoPen 1.5 uses
Novolin PenFill@*, a 1.5mL cartridge
(150 U) of human insulin (recombinant
DNA origin) in an NPH, regular, or 70/30
formulation. By dialing a dose, patients
can select delivery of up to 40 U per dose
in 1-U increments. The Novolin Pretilled
disposable insulin pen contains 150 U of
human insulin and allows delivery of up
to 58 U per dose in 2-U increments. A
4-week clinical studf with the Novolin
Prefilled system showed significant patient
acceptance among 64 insulin users, 98%
of whom found the pen convenient and
easy to use. The present study employed
two large, multicenter surveys to assess
users’ acceptance of the Novolin Prefilled
and NovoPen 1.5 insulin delivery systems.
PATIENTS AND METHODS
Patients
Centers for the two study surveys were
selected on the basis of geographic con-
siderations and willingness and ability to
carry out the survey. The first survey,
which included 803 insulin users in 24
centers across the United States, evalu-
ated the Novolin Prebilled pen using the
following variables: (1) patients’ partici-
pation in normal daily activities and so-
cial activities compared with their partic-
ipation while using a traditional vial and
syringe; (2) patients’ compliance with in-
sulin, diet, and exercise regimens; and
(3) patients’ overall sense of well-being.
The second survey, which included 507
insulin users in 64 centers, assessed the
487

effect of the NovoPen 1.5 on patients’ at-
titudes about taking insulin, improving
compliance, and perceiving their comfort.
Patients were eligible to participate in
either survey if they had type 1 or type 2
diabetes; could administer insulin, as as-
sessed by a health-care professional; could
read and understand English; and could
follow printed instructions. On considera-
tion by the relevant institutional review
boards, it was determined that approval
was not required because participation in
these surveys involved no risk to the sub-
jects. A health-care professional asked the
patient if he or she wanted to participate,
and the patient agreed or refused. Patients
who chose to participate did not have to
pay for the insulin delivery system.
Patients in both groups were given the
insulin pen delivery system by a research
coordinator (a physician, nurse, or other di-
abetes educator), who recorded the patient’s
name and assigned the patient an identifi-
cation number. During the initial site visit,
which was a routine medical visit at a physi-
cian’s office, patients were instructed in the
proper use of the insulin pen, according to
the approved product labeling. Each patient
was given sufficient supplies to last 3
weeks, and arrangements were made for
their completion of the survey. All patients
were informed that the surveys were sup-
ported by Novo Nordisk Pharmaceuticals
Inc. (Princeton, New Jersey) and that the
research sites would receive an honorarium
for participating. Investigators received an
honorarium but were not paid for enrolling
patients or prescribing the delivery systems.
Patients in the first survey (Novolin Pre-
filled insulin pen vs traditional vial and sy-
ringe) completed the first two parts of a
three-part questionnaire during the initial
site visit. The first part contained 7 general
questions about demographics and diabetes
488
CLINICAL THERAF’EUTICS”
history; the second part contained 18 ques-
tions about patients’ current treatment reg-
imen with insulin vial and syringe. The lat-
ter part included questions on the effects
on patients’ lifestyle of using the traditional
vial and syringe and on their feelings about
using this delivery system.
Patients completed the third part of the
questionnaire at the physician’s office after
they had used the disposable insulin pen
for 3 weeks. This contained 26 questions
comparing compliance and control, effects
on lifestyle, and opinions and perceptions
while using the new delivery system with
experiences while using the vial and sy-
ringe. Each question in the second part of
the questionnaire was repeated in the third
part to allow comparison of patients’ expe-
riences with the insulin vial and syringe
and the Novolin Prefilled insulin pen.
Patients in the second survey (NovoPen
1.5 vs traditional vial and syringe) com-
pleted a questionnaire containing 25 ques-
tions about their history and experience
with insulin and their attitudes and opin-
ions about the NovoPen 1.5 compared
with the vial and syringe after using the
insulin pen for 3 weeks.
The two surveys contained questions
that had been used in a previous study4 as
well as questions based on the input of di-
abetes professionals practicing in a variety
of settings throughout the United States.
The data were tabulated by Distinctive
Marketing, Inc. (Montclair, New Jersey).
No data were collected retrospectively. Not
all patients answered all questions.
RESULTS
Demographic Characteristics
More extensive information was ob-
tained on the group using the Novolin Pre-
M.R. GRAPP AND M.A. McCLANAHAN

filled delivery system (Table I) than on
the group using the NovoPen 1.5 (Table
II). Adverse event data were not collected.
A wide range of insulin-using patients
participated in the Novolin Prefilled sur-
vey. Four hundred sixty-four (58%) of the
803 patients were 36 to 65 years of age,
190 (24%) were 266 years of age, and 149
(19%) were 135 years of age. Two hundred
sixty (32%) of 801 participants had been
taking insulin for 1 to 5 years; 355 (44%)
of 801 had been taking insulin for >5 years.

Table I. Demographic characteristics of participants in the Novolin Prebilled@* insulin

delivery system survey (N = 803, but not all patients answered all questions).

Variable No. (%) of Patients

Age (Y)
13s 149/803 (19)
3655 299/803 (37)
566s 1651803 (21)
266 190/803 (24)
Type of diabetes
Type 1 2X/786 (32)
Type 2 453/786 (58)
Not certain 81/786 (10)
Length of time receiving insulin (y)
<l 186/801 (23)
1-s 260/801 (32)
>S 355/801 (44)
Type of human insulin used
70130 295l779 (38)
NPH 141/779 (18)
NPH + regular 227l779 (29)
NPH + regular + 70/30 26l779 (3)
NPH + 70/30 81779 (1)
Regular 19/779 (2)
Regular + 70/30 12/779 (2)
Other 51/779 (7)
Brand of insulin used
Humulin@t 4131763 (54)
Novolin 298l763 (39)
Novolin + Humulin 261763 (3)
Not certain 26l763 (3)
Current insulin regimen
QD 105/745 (14)
BID 431/745 (58)
2TID 209i745 (28)

*Trademark of Novo Nordisk A/S, Copenhagen, Denmark.

‘Trademark of Eli Lilly and Company, Indianapolis, Indiana.

489
 CLINICAL THERAPEUTICS’

Table II. Demographic characteristics of participants in the NovoPen@ 1.5* insulin delivery
system survey (N = 507, but not all patients answered all questions).

Variable No. (%) of Patients

Length of time receiving insulin (y)’

<l 96/507 (19)
l-3 86/507 ( 17)
4-9 106/507 (21)
210 219/507 (43)
Type of human insulin used
70/30 461507 (9)
NPH 76/507 (15)
NPH + regular 2291507 (45)
Regular 301507 (6)
Regular + other 96/507 (19)
Other 301507 (6)
Brand of insulin used
Humulin@* 3041507 (60)
Novolin 143/507 (28)
New to insulin 50/507 (9)
Other 10/507 (2)
Current insulin regimen
QD 401504 (8)
BID 126/504 (25)
TID 338/504 (67)

*Trademark of Novo Nordisk A/S, Copenhagen, Denmark.

tMean = 8.51 y.
*Trademark of Eli Lilly and Company, Indianapolis, Indiana.

Approximately one third of the patients had
type 1 diabetes, and 72% (536/745 patients)
took insulin injections once or twice daily.
Table II presents demographic data for
the 507 patients who used the NovoPen
1.5. Age and sex data were not collected
in this group. Almost two thirds (64%) of
the patients had been taking insulin for 24
years, with 219 patients (43%) taking in-
sulin for 210 years. Fifty (10%) of the
507 patients had never taken insulin be-
fore participating in this survey and thus
were not asked to answer questions com-
paring the syringe and pen.
Responses to the Novolin Prefilled
Delivery System Survey
When patients’ attitudes and perceptions
about taking insulin before and after using
the Novolin Prebilled disposable insulin pen
were compared, substantial changes in out-
look were noted. Table III presents patients’
responses to the Novolin Prefilled delivery
system survey. The responses are grouped
by category (medical, social/lifestyle, con-
venience, and overall evaluation) and in-
clude attitudes toward both the Novolin
Prefilled delivery system and the insulin
M.R. GRAFF AND M.A. McCLANAHAN

vial and syringe. Participants rated the
Novolin Pretilled system higher than the
syringe and vial on every measure in all
four categories.
Medical
Six hundred seventy-two (85%) of 791
patients did not miss any insulin injec-
tions during the 3 weeks that they used
the Novolin Prefilled system, and 410
(52%) of 789 patients reported that they
rarely or never had a high blood glucose
level during this time. In contrast, 566
(72%) of 789 patients indicated that they
did not miss injections with the vial and
syringe, and 275 (35%) of 778 reported
rare or no high blood glucose levels. Ad-
ditionally, 715 (90%) of 794 patients re-
ported little or no pain on injection with
the Novolin Prefilled system (using the
NovoFine 30 insulin needle), compared
with 389 (50%) of 784 patients reporting
little or no pain with the vial and syringe.
SociaULifestyle
The Novolin Prebilled delivery system
had a positive impact on patients’ social
activities and lifestyle, particularly on their
ease of maintaining dietary and exercise
regimens: 603 (79%) of 763 patients re-
ported that they found it easy to eat ap-
propriately, compared with 326 (42%) of

Table III. Patients’ responses to the Novolin Prebilled@‘*insulin delivery system versus the
traditional vial and syringe (N = 803, but not all patients answered all questions).

Response Novolin Prefilled (%) Vial and Syringe (%)

Medical
Have little or no pain on injection 90 50
Did not miss any injections 85 72
Feel better when using this method 75 47
Rarely/never experienced high blood glucose 52 36
Social/lifestyle
Easy to eat appropriately 79 42
Easy to exercise appropriately 76 38
Equally likely to take insulin at home or away 64 31
Have a better social life on this treatment 56 17
Am more active when using this treatment 46 23
Convenience
Easy to take insulin 92 39
Satisfied with this delivery system 84 30
Convenience of treatment 79 32
Find the treatment flexible 75 29
Find the method of administration convenient 79 34
Overall evaluation
Preferred delivery system 79 7
Positive impact on well-being 75 47
Willing to continue using this treatment 88 32
Would recommend this method to someone else 91 39

*Trademark of Novo Nordisk A/S, Copenhagen, Denmark.

491

776 patients who indicated the same for
the vial and syringe. Five hundred sev-
enty-seven (76%) of 759 patients reported
that it was easy to exercise during the 3
weeks they used the Novolin Pretilled pen,
compared with 304 (39%) of 780 patients
who reported ease of exercising while us-
ing the insulin vial and syringe.
Convenience
As shown in Table III, all responses re-
lated to the convenience of the delivery
system were positive in more than twice
as many patients using the Novolin Pre-
filled pen as the vial and syringe. For ex-
ample, 299 (38%) of 793 patients found
it “easy to take insulin” with the syringe,
whereas 738 (93%) of 793 patients re-
ported the same for the insulin pen. Sim-
ilar differences were observed for satis-
faction levels and flexibility of treatment.
Overall Evaluation
When asked about their personal pref-
erence, 629 (79%) of 792 patients indi-
cated that they preferred the Novolin Pre-
filled system; 55 (7%) of 792 patients
preferred the vial and syringe. Addition-
ally, 591 (75%) of 788 patients stated that
the insulin pen had a positive effect on
their overall well-being, compared with
369 (47%) of 785 patients reporting such
an effect with the vial and syringe. Pa-
tients were also more willing to continue
using the insulin pen (88% vs 32%) and
more willing to recommend this delivery
system to others (91% vs 39%) compared
with the vial and syringe.
Responses to the NovoPen 1.5 Survey
Medical
In assessing the degree of pain associ-
ated with injecting insulin, 428 (90%) of
492
CLINICAL THERAPEUTICS”
the 476 patients who answered this ques-
tion said that the NovoFine needle caused
little or no pain, with only 48 (10%) pa-
tients indicating that they found it painful.
In contrast, 63 (38%) of 165 patients said
that their previous insulin syringe needle
caused little or no pain, with 102 (62%)
of 165 patients reporting moderate-to-
severe pain (figure). In addition, 333
(73%) of 456 patients believed that the
dosing mechanism of the NovoPen 1.5
was more accurate than that of the insulin
syringe (Table IV).
SociaLfZifestyle
As shown in Table IV, 426 (89%) of
479 patients considered the NovoPen 1.5
to be more socially acceptable than the
traditional vial and syringe, and thus 432
(89%) of 488 felt more comfortable in-
jecting insulin in public.
Convenience
Four hundred eighty-two (98%) of 492
patients considered the NovoPen 1.5 easy
to use, with 409 (86%) of 475 indicating
that it was easier to use than the vial and
syringe. Four hundred twenty (86%) of
488 patients said that it took less time to
prepare and administer injections with the
pen, and 351 (77%) of 456 patients indi-
cated that using the pen made it easier for
them to comply with their treatment regi-
men (Table IV).
Overall Evaluation
One hundred twenty-three (70%) of 175
patients had an improved attitude toward
insulin therapy after using the NovoPen
1.5, with 467 (97%) of 481 patients indi-
cating that they would recommend this
delivery system to another person. Two
hundred fifty-one (85%) of 295 patients
rated the pen as more comfortable than
M.R. GRAFF AND M.A. McCLANAHAN

Little or no pain

u Painful

62

36

0 I- I Insulin
Vial and Syringe
(n = 165)
Needle in
NovoPen 1.5
(n = 476)
10

Figure. Comparison of injection comfort levels with traditional insulin vial and syringe
and with NovoPen@’ 1.5. NovoPen 1.5 contains a NovoFine@ 30 insulin needle.
Both NovoPen and NovoFine are trademarks of Novo Nordisk A/S, Copenhagen,
Denmark.

the vial and syringe, and 377 (97%) of
389 patients planned to continue using the
NovoPen 1.5 (Table IV).
DISCUSSION
The serious long-term complications of
diabetes (eg, kidney disease, hyperten-
sion, stroke, cardiovascular disease, nerve
disease, periodontal disease, and blind-
ness) mandate that diligent attention be
given to disease management. The Dia-
betes Control and Complications Trial5
demonstrated that when diabetes is well
managed, the risks of these complications
are reduced. Maintaining glycemic con-
trol with appropriate insulin dosing is one
of the most important aspects of disease
management, which also includes regular
glucose monitoring, frequent physical ex-
aminations, dietary modifications, a regu-
lar exercise program, and in-depth educa-
tion about diabetes and its treatment.
Education about the disease is crucial
for patients with diabetes, but information
must be conveyed in a nonthreatening
manner. Many patients resist the idea of
insulin therapy, either because they are
afraid of the injections3 or because they
believe that insulin therapy represents a
last resort and underscores their failure to
manage their disease through lifestyle
changes.* An important goal for diabetes
educators is to communicate honestly with

493

Table IV. Patients’ responses to the NovoPen@* 1.5 insulin delivery system.
Response
Medical
Dosing mechanism is more accurate
Little or no pain
Social/lifestyle
Pen is more socially acceptable than syringe
Feel more comfortable using this method in public
Convenience
It is easy to use
Easier to use than vial and syringe
Time for preparation and injection is less than with syringe
Compliance is easier
Overall evaluation
Attitude toward insulin therapy improved
Pen is more comfortable than syringe
Plan to continue using
Would recommend this method to someone else
*Trademark of Novo Nordisk A/S, Copenhagen,
patients, yet in a sensitive and compas-
sionate manner, to help them develop a
positive and “proactive” attitude toward
managing their own illness.’
It is estimated that 60% to 80% of pa-
tients with diabetes who use a conven-
tional vial and syringe carry out some as-
pect of insulin administration incorrectly
(eg, timing, quantitative errors).6g7 The
present two surveys suggest that patients
may be much more likely to adhere to
their insulin regimen when they use the
Novolin Prefilled or NovoPen 1.5 insulin
pen: 527 (67%) of 788 patients indicated
that they felt more confident about man-
aging their illness when using the Novolin
Prefilled system, and 351 (77%) of 456
patients said that the NovoPen 1.5 made
it easier for them to comply with their
treatment regimen. These results are con-
sistent with the outcomes of a study by
494
CLINICAL THERAPEUTICS”
No. (%) of Patients
333i456 (73)
4281476 (90)
4261479 (89)
4321488 (89)
482/492 (98)
409J475 (86)
4201488 (86)
351/456 (77)
123075 (70)
25 l/295 (85)
377/389 (97)
467/48 1 (97)
Denmark.
Plevin and Sadur,4 in which 78% of pa-
tients felt in control of their diabetes while
using the Novolin Prefilled insulin pen
and 98% found the system convenient and
easy to use.
Another interesting outcome is that pa-
tients felt they received more accurate
doses with the insulin pens than they did
with the traditional vial and syringe. In the
NovoPen 1.5 survey, 333 (73%) of 456
patients reported that this dosing mecha-
nism was more accurate than the syringe.
Although a question on the accuracy of
dosing was not included in the Novolin
Prefilled survey, 410 (52%) of 789 pa-
tients reported that they rarely or never
experienced a high blood glucose level
while using the pen, compared with 275
(36%) of 778 patients who reported a high
blood glucose level while using the vial
and syringe, suggesting that more accurate
M.R. GRAFF AND M.A. McCLANAHAN
administration of doses may have oc-
curred. Certainly the fact that 672 (85%)
of 791 patients missed no injections dur-
ing the 3-week period is an encouraging
finding. In the Plevin and Sadur study,4
67% of patients indicated that they were
not worried about hypoglycemia while us-
ing the Novolin Prebilled insulin pen.
The potential for more accurate dosing
suggests a particular advantage for older
patients, who represent nearly half of the
individuals with diabetes. Whether be-
cause of diminished manual dexterity or
other factors accompanying aging, pa-
tients aged ~65 years sometimes have dif-
ficulty drawing up accurate doses with a
vial and syringe. The pens’ dial-a-dose
mechanism and cartridges may minimize
this problem, as well as the possibility of
accidentally drawing up air bubbles.
The insulin pens do have some limita-
tions, however. Although regular and NPH
insulin are available in cartridges, the only
premixed regular and NPH insulin available
in cartridges is 70/30 (70% NPH and 30%
regular human insulin). Until other mixtures
become available, patients who require a
mixture other than 70/30 must take two in-
jections. Additionally, the daily costs of in-
sulin administration using the Novolin Pre-
filled and NovoPen 1.5 delivery systems are
$1.82/d and $1.76/d, respectively, compared
with $1.05/d for the traditional insulin vial
and syringe. However, when compliance
with a medication regimen improves, the
long-term costs of complications and hospi-
tal admissions may be reduced.
The findings of these two surveys must
be interpreted in the context of the sub-
jects who participated. The results reflect
the opinions of subjects who accepted the
invitation to participate and were willing
to use a pen instead of the traditional in-
sulin syringe. As such, they may not rep-
resent the general population of patients
who use insulin. However, the method of
selecting patients was appropriate to the
objective of the surveys, namely, to com-
pare users’ perceptions of the pen versus
the syringe.
CONCLUSIONS
A majority of the patients found the two
pens to be superior to the traditional in-
sulin vial and syringe in all categories sur-
veyed. This increased acceptance of an
alternative insulin delivery system might
be expected to translate into increased
acceptance of and compliance with treat-
ment regimens.
ACKNOWLEDGMENT
These studies were supported by grants
from Novo Nordisk Pharmaceuticals Inc.,
Princeton, New Jersey.
Address correspondence to: Marilyn R.
Graff, RN, CDE, Diabetes Care Team,
12744 San Fernando Road, Sylmar, CA
91342.
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