Journal of Diabetes Science and Technology
` Volume 2, Issue 2, March 2008
` © Diabetes Technology Society
`
`COMMENTARY
`
`Insulin Pen—The “iPod” for Insulin Delivery
`(Why Pen Wins over Syringe)
`Ernest Asamoah, M.D., FACP, FACE, FRCP
`
`Abstract
`Diabetes affects most aspects of everyday life and places considerable responsibility on the patient; therefore,
`without patient acceptance of what we offer, the therapy is unlikely to be adhered to especially when that
`therapy happens to be insulin injection. In 2008, almost every physician/health care provider carries new and
`sleek cell phones (because the newer ones are well designed and function better). Why these same providers
`continue to prescribe insulin via syringes in 2008 is something that I cannot fathom. Previously, some insurance
`companies only paid for vials and there was no other choice, but today almost all insurance pay for pens and
`so the “insurance reason” is no longer tenable. Since Banting and Best discovered insulin in 1921, scientists have
`continued to improve the types of insulin (making them mimic physiology more closely in order to minimize
`hypoglycemia and improve glycemic control as seen with the latest analog insulins). In the same manner, the
`delivery process of insulin has also continued to evolve to make it easier and more acceptable to patients.
`Studies have shown that patients prefer device use over traditional vials/syringes. Pen devices used to inject
`insulin lead to better compliance, are quicker to inject, dosing is much more accurate, and, surprisingly, are
`more cost effective. I challenge my colleagues to take full responsibility for what their patients use. If a provider
`believes in pen devices, most of his/her patients will use them. The products your patients use is a direct
`reflection of what you practice. Educating providers to change their beliefs and practices is key to moving
`American diabetic patients from syringes to pen devices.
`
`J Diabetes Sci Technol 2008;2(2):292-296
`
`Introduction
`
`Glycemic control is so critical for our diabetic
`
`patients because every major study published has
`shown convincingly that lower hemoglobin A1c (HbA1c)
`equals a reduction in diabetes-related complications.1
`For most patients though, the only way to prevent or
`
`minimize these complications is to use insulin therapy
`because of the progressive nature of type 2 diabetes.
`
`For decades, insulin was delivered only via vials and
`syringes with larger bore needles that caused a lot of
`
`Author Affiliation: Diabetes and Endocrinology Consultants, Indianapolis, Indiana
`
`Abbreviations: (HbA1c) hemoglobin A1c
`
`Keywords: analog insulin, insulin delivery device, pen, vial/syringe
`
`Corresponding Author: Ernest Asamoah, M.D., Diabetes and Endocrinology Consultants, 7440 N. Shadeland Avenue, Suite 200, Indianapolis,
`IN 46250; email address easamoah@ecommunity.com
`
`292
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`Insulin Pen—The “iPod” for Insulin Delivery (Why Pen Wins over Syringe)
`
`Asamoah
`
`pain. Many people with diabetes still believe that these
`needles are still large and painful, but in 2008, this could
`not be further from the truth.
`
`D.
`
`Another important advantage of pen devices is their
`portability and their ability to be used discreetly.
`These features help render insulin therapy more
`socially acceptable, especially to younger patients
`who may be sensitive to peer group approval
`and the embarrassment and stigma surrounding
`injections. Several studies suggest that patients feel
`less conspicuous carrying a pen device and more
`comfortable about using it in public compared with
`using a syringe.
`
`E.
`
`Pen devices (e.g., NovoPen®) have been shown to be
`more accurate than syringes for the delivery of doses
`of insulin ≤5 units2,3 and so may benefit children and
`adolescents who usually require smaller doses.
`
`F.
`
`Patients across all age spectrums have unique
`challenges for which pen devices help address.
`
`For children, needle fear is minimized significantly
`(e.g., with the new Novo autocover needle).
`
`Adolescents like pen devices for their social
`acceptability—they are “cool.”
`
`Older patients with diabetes who have comorbidities
`or disabilities (e.g., visual impairment, impaired
`motor skills) that may exacerbate the difficulties of
`self-injection and increase the risk of dosing errors
`can find solace in using a pen-injecting device that
`overcomes some of their limitations.
`
`• • •
`
`Indeed, studies suggest that insulin preparation by
`elderly patients is highly inaccurate4; in one study in
`patients >60 years, the insulin dosage became less
`accurate as age increased, such that two-thirds of patients
`>75 years were found to be injecting the wrong dose.5
`Patients with visual impairment have been shown to feel
`more active and more relaxed about insulin injection
`when using a NovoPen-based regimen6 with its useful
`audible clicks. These benefits are likely to be applicable
`to other pen devices.
`
`Clinical Studies Comparing Pens and
`Syringes
`Results from two multicenter, randomized, open-label,
`•
`crossover trials in insulin-experienced patients with
`type 2 diabetes were analyzed. The trials assessed the
`efficacy and safety of the Novolog Mix 70/30 FlexPen,
`as well as preference for this device compared with
`a vial/syringe (n = 121). Results showed that 74% of
`
`There are numerous reasons why using pen devices
`make a whole lot of sense. Compliance with treatment
`is better because a pen device is easier to carry around,
`easy to use, provides greater dose accuracy, and is more
`satisfactory to patients as compared with a syringe.
`Injecting with devices makes the process discreet, and
`the overall cost of managing diabetes is also reduced.
`
`The surprising fact is that among industrialized countries,
`the United States ranks last in terms of pen usage
`by diabetic individuals, even though the use of pen is
`increasing.
`
`Advantages of Pens over Syringes
`
`A.
`
`B.
`
`The current disposable pens are easy to teach, and
`for me that has been the best part of starting insulin
`therapy. Even when my nurses or medical assistants
`are too busy to teach patients, I can do so within
`5 minutes and give the patients a handout with
`further instructions to take home.
`
`Using 30/31-gauge short needles with pens has
`significantly reduced the needle phobia that patients
`have about taking injections. The reason why these
`needles are less painful is that they do not have to be
`inserted into a vial first (thereby destroying the fine coating
`on the tip, hence the pain on injection).
`
`Many times I consult patients who need to start
`insulin and they flatly refuse (for a number of reasons).
`A classic case report is as follows. A 39-year-old male
`patient with an HbA1c of 9.5% who has had diabetes
`for 8 years (after severe pancreatitis) was referred for
`further management. He told me that if he was to
`go on insulin, he would rather die than do so. After
`discussing the myths about insulin and reassuring
`him of the benefits, the biggest hurdle for him was
`the fact that he had to inject himself. When I showed
`him a pen device with the needle and the process, all
`his resistance faded, he walked out of my office ready
`to take insulin, and is now a happy patient. This
`scene is literally repeated several times a month in
`my office.
`
`C.
`
`Teaching patients how to use pens in the office as
`opposed to sending them to an off-site office reduces
`some of the hassle of insulin initiation.
`
`J Diabetes Sci Technol Vol 2, Issue 2, March 2008
`
`293
`
`www.journalofdst.org
`
`Mylan Ex.1067
`Mylan v. Sanofi - IPR2018-01676
`
`

`

`Insulin Pen—The “iPod” for Insulin Delivery (Why Pen Wins over Syringe)
`
`Asamoah
`
`patients preferred the Novolog Mix 70/30 FlexPen
`compared with the vial/syringe device.7
`
`•
`
`A 2001 mail survey examined respondents’ preferences
`for pen devices and vials/syringes between insulin
`naïve and insulin users.8 A total of 242 type 1 and 2
`patients (99 were insulin users and 143 were
`insulin naïve) completed a 19-item self-administered
`questionnaire designed to assess their expectations of
`attributes related to these devices. These items were
`analyzed on a five-point Likert-type scale with higher
`scores indicating greater agreement that attributes
`met expectations. Finally, the composite scores for ease
`of use, activity interference, and social acceptability were
`used to further examine differences among patients
`regarding their preference for either syringes or pens.
`
`The overall preference was higher for the pen device
`compared with the vial/syringe (Table 1). Social
`acceptability was the strongest predictor of preference
`for the pen device. For current insulin users, social
`acceptability and ease of use were the significant
`predictors of preference for pens.
`
`The inference therefore is for providers to place
`emphasis on ease of use and convenience of pen devices
`when initiating insulin therapy.
`
`scale (1 = almost never, 4 = almost always) with
`a maximum fear score of 32. The patients also
`completed a preference survey at week 24.
`
`These patients reported a significantly lower fear of
`self-injection after using the InnoLet device compared
`to the vial/syringe method (mean ± SEM: 9.5 ± 0.2
`vs 11.2 ± 0.4; p < 0.0001). The majority of patients
`(71.5%) indicated a preference for the InnoLet device
`compared to the vial/syringe method (p < 0.0001).
`
`Cost Benefit of Pens vs Syringes
`The argument in the past has been that pen utilization
`for insulin delivery is more costly than syringes. That
`argument is no longer tenable, as most insurance
`companies cover these pen devices. Moreover, studies
`show that the overall cost of health care delivery is
`reduced with pens.
`
`A.
`
`In a 2007 observational study, initiating insulin
`therapy using a preloaded insulin pen was shown
`to be associated with reduced health care utilization
`compared with using traditional vials and syringes,
`and just as in a previous study in 2006, the reduced
`use of health care resources translates directly into
`cost savings.10
`
`Table 1.
`Comparison of Pens/Syringes
`Pens
`
`Ease of use
`
`Patient acceptance
`
`Reduces needle phobia
`
`Dosing accuracy
`
`Cost-effective
`
`Yes
`
`Yes
`
`Yes
`
`Yes
`
`Yes
`
`Patient preference
`
`Overwhelming yes
`
`Convenience
`
`Yes
`
`Syringes
`
`No
`
`No
`
`No
`
`No
`
`No
`
`No
`
`No
`
`•
`
`Another study evaluated patients’ preferences for an
`insulin delivery system by comparing a disposable
`device (InnoLet) to a vial/syringe.9 This was a
`prospective, randomized, open-label, two-period,
`crossover study. A total of 262 (mean age of 60)
`type 1 or 2 diabetic patients were enrolled with 162
`completing the study.
`
`Eight-item diabetes fear of self-injection questionnaires
`were administered at baseline, week 12, and week
`24. These items were rated on a four-point Likert
`
`Pawaskar et al.10 accessed the North Carolina Medicaid
`program patient-claims database to compare costs
`related to starting of insulin therapy using either pens
`(NovoPen or FlexPen, Novo Nordisk, Inc.) or syringes.
`A total of 1330 type 2 diabetic patients (1162 using
`syringe vs 168 using pen) patients enrolled in the
`Medicaid program between September 2001 and July
`2006 and who had completed at least 24 months
`follow-up were analyzed.
`
`Excluding prescriptions cost, the total annual health
`care cost averaged roughly $14,900 in the pen group
`and $32,000 in the syringe users. The cost savings
`were driven primarily by a reduced use of hospital-
`based treatment (approximately $1200 and $5000,
`respectively).
`
`Even though the initial cost of an insulin pen is
`greater than that for syringes (looking at the amount
`one pays at the pharmacy), the overall cost benefits of
`using pens exceed those for syringe use.
`
`Pawaskar and associates10 concluded that “diabetes
`management programs should therefore be designed
`
`J Diabetes Sci Technol Vol 2, Issue 2, March 2008
`
`294
`
`www.journalofdst.org
`
`Mylan Ex.1067
`Mylan v. Sanofi - IPR2018-01676
`
`

`

`Insulin Pen—The “iPod” for Insulin Delivery (Why Pen Wins over Syringe)
`
`Asamoah
`
`with components to improve patients’ awareness
`of insulin devices and encourage their use in low-
`income minority populations with type 2 diabetes to
`prevent excessive expenditures for other health care
`resources.”
`
`B.
`
`Lee and colleagues11 also showed similar cost-
`effectiveness when insulin pens were used in preference
`to vials/syringes in 2006. This study looked at patients
`records and showed that converting from vials/syringes
`was associated with a significant improvement in
`medication adherence and a reduced likelihood of
`experiencing a hypoglycemic event (odds ratio = 0.50;
`95% confidence interval = 0.37–0.68; p < 0.05).11
`
`Even more practical (for those concerned about
`cost) was that all-cause annual treatment costs were
`reduced by $1590 per patient (from $16,359 to $14,769;
`p < 0.01) (Figure 1).
`
`The key indicators for good diabetes management
`were impacted in this study and also the overall cost
`to the health care system was reduced by going from
`vials to pens.
`
`Modern Delivery Devices
`Various pen devices have been on the market, including
`Novo Nordisk’s FlexPen, InDuo; Sanofi-Aventis’ OptiClik,
`Solostar; and Lilly’s HumaPen, Memoir (Figure 2).
`These devices are all designed to be patient friendly.
`Diabetes educators, nurse practitioners, and even the
`sales representatives of the companies that market these
`devices offer training on them. DVDs and other teaching
`materials are also readily available to providers and
`patients.
`
`Device Preference
`Providers may have personal preferences on which
`devices are better. I believe that what is more important
`is to initially convince patients to go on insulin sooner (if
`needed) in order to get glycemic control and to get them
`to use analog insulins (which cause less hypoglycemia).
`Using pens with analog insulins is a win–win situation.
`Again, as with cell phones, in 2008 there are many new
`devices and all offer various features that may appeal to
`different people (one size does not fit all).
`
`Conclusion
`The diabetic patient is faced with many challenges in
`managing their condition and the least that providers
`
`Figure 1. FlexPen vs vial/syringe results: adherence, hypoglycemia,
`and health care costs. From Lee et al.11
`
`Figure 2. Pen devices used for injecting insulin.
`
`can do for them is to make their lives easier. Discussing
`and prescribing pen delivery devices to use for insulin
`injection are major help we can provide.
`
`The benefits of using devices are clear—pen devices
`are preferred by patients because they make insulin
`administration easy and convenient. They also offer
`lifestyle flexibility and reduced pain, both of which are
`considered likely to translate into enhanced quality of
`life and compliance. Remember, your patients reflect you
`in many ways and what you discuss or not discuss is
`what they will do.
`
`I often ask providers what their preference would be if
`they had diabetes and all of them say they prefer pens
`over syringes. “What is good for the goose (physician)
`is also good for the gander (patients)” so unless cost is
`truly a barrier, there is no reason whatsoever to start
`insulin therapy with a vial/syringe.
`
`J Diabetes Sci Technol Vol 2, Issue 2, March 2008
`
`295
`
`www.journalofdst.org
`
`Mylan Ex.1067
`Mylan v. Sanofi - IPR2018-01676
`
`

`

`Insulin Pen—The “iPod” for Insulin Delivery (Why Pen Wins over Syringe)
`
`Asamoah
`
`8.
`
`9.
`
`10.
`
`11.
`
`Stockl K, Ory C, Vanderplas A, Nicklasson L, Lyness W, Cobden D,
`Chang E. An evaluation of patient preference for an alternative
`insulin delivery system compared to standard vial and syringe.
`Curr Med Res Opin. 2007;23(1):133-46.
`Summers KH, Szeinbach SL, Lenox SM. Preference for insulin
`delivery systems among current insulin users and nonusers. Clin
`Ther. 2004;26(9):1498-505.
`Pawaskar MD, Camacho FT, Anderson RT, Cobden D, Joshi AV,
`Balkrishnan R, Health care costs and medication adherence
`associated with initiation of insulin pen therapy in medicaid-
`enrolled patients with type 2 diabetes: a retrospective database
`analysis. Clin Ther. 2007;29:1294-305.
`Lee WC, Balu S, Cobden D, Joshi AV, Pashos CL. Medication
`adherence and the associated health-economic impact among
`patients with type 2 diabetes mellitus converting to insulin pen
`therapy: an analysis of third-party managed care claims data. Clin
`Ther. 2006;28(10):1712-25.
`
`The question as to which pen is more acceptable to
`patients is not what I intended to address here because I
`think that is a secondary issue when one looks at the big
`picture. As long as the pen device chosen is acceptable
`to patients and makes them comply more with treatment,
`the issue of which pen is used is of secondary importance,
`especially when larger insulin doses are delivered.
`
`Therefore, I argue strongly that a pen device should be
`the first option offered to new insulin starters and that
`patients already using vials should also be offered the
`opportunity to convert to pens (unless they choose not
`to or there are other compelling reasons not to do so).
`
`This can only happen if providers know about the new
`insulin pens available and are educated about them as
`well as feel comfortable using them. Any provider taking
`care of diabetic patients owes it to his/her patients to
`offer the best option, and in this situation (vials vs pens),
`there is a clear winner—pens.
`
`Acknowledgment:
`Thanks go to Dr. David Klonoff for inviting me to write this
`commentary and for some material support.
`
`Disclosure:
`I am a consultant and on the speaker bureau for Sanofi-Aventis, Novo
`Nordisk.
`
`2.
`
`3.
`
`4.
`
`References:
`The Diabetes Control and Complications Trial Research Group.
`1.
`The effect of intensive treatment of diabetes on the development
`and progression of long-term complications in insulin-dependent
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`Gnanalingham MG, Newland P, Smith CP. Accuracy and
`reproducibility of low dose insulin administration using pen-
`injectors and syringes. Arch Dis Child. 1998;79:59-62.
`Gnanalingham MG, Newland P, Smith CP. An evaluation of
`NovoPen, BD-Pen, and syringe devices at small doses of insulin
`[abstract no. P118]. British Diabetic Association’s Medical and
`Scientific Section Spring Meeting; 1998 Mar 25-27; Heriot Watt
`University, Edinburgh; 1998. p. S49.
`Coscelli C, Calabrese G, Fedele D, Pisu E, Calderini C, Bistoni S,
`Lapolla A, Mauri MG, Rossi A, Zappella A. Use of premixed insulin
`among the elderly. Reduction of errors in patient preparation of
`mixtures. Diabetes Care. 1992; 15(11):1628-30.
`Liebermeister H, Sammler A. Problems of the elderly, insulin
`injecting diabetic patients in ambulatory care [in German].
`Versicherungsmedizin. 1990;42(2):59-64.
`Hyer SL, Froyd HE, Kohner EM. Effect of the NovoPen on
`glycemic control and patient independence in diabetics with visual
`impairment. Practical Diabetes Int. 1988; 5:197-9.
`Korytkowski M, Bell D, Jacobsen C, Suwannasari R; FlexPen
`Study Team. A multicenter, randomized, open-label, comparative,
`two-period crossover trial of preference, efficacy, and safety
`profiles of a prefilled, disposable pen and conventional vial/
`syringe for insulin injection in patients with type 2 or 3 diabetes
`mellitus. Clin Ther. 2003;25:2836-48.
`
`5.
`
`6.
`
`7.
`
`J Diabetes Sci Technol Vol 2, Issue 2, March 2008
`
`296
`
`www.journalofdst.org
`
`Mylan Ex.1067
`Mylan v. Sanofi - IPR2018-01676
`
`