DIABETES TECHNOLOGY & THERAPEUTICS
`Volume 12, Supplement 1, 2010
`© Mary Ann Liebert, Inc.
`DOI: 10.1089/dia.2009.0179
`
`Reusable and Disposable Insulin Pens
`for the Treatment of Diabetes:
`Understanding the Global Differences in User Preference
`and an Evaluation of Inpatient Insulin Pen Use
`
`Riccardo Perfetti, M.D., Ph.D.
`
`Abstract
`
`Insulin is essential for the management of type 1 diabetes and is more commonly being used for the treatment of
`type 2 diabetes. Insulin pen devices were first introduced over 20 years ago and have evolved to provide
`significant practical advantages compared with the vial and syringe. Pen devices are now used by patients with
`diabetes worldwide, but there are marked geographical variations in the use of reusable and disposable pens. In
`some countries the vial and syringe is still the most popular method of administering insulin, whereas in other
`countries the use of reusable or disposable pens is more prevalent. Therefore, the aim of this review is to discuss
`the factors that seem to be involved in these differences, which include patient access to insulin, cost, and
`physician/patient awareness and preference. Inpatient use of insulin is also common, and the use of insulin pens
`could offer substantial benefits in this patient population, not only during the admission period but also after
`discharge from the hospital. However, the evidence base for inpatient use is still weak, and more studies are
`needed to investigate the use of insulin pens in this patient population.
`
`Introduction
`
`THE PREVALENCE OF DIABETES worldwide was estimated to
`
`be in excess of 170 million patients in 20001 and is ex(cid:173)
`pected to increase to over 440 million among individuals 20-79
`years of age by 2030.2 Most of the cases will have type 2 dia(cid:173)
`betes, as type 1 diabetes represents less than 10% of all cases of
`diabetes. In type 2 diabetes, standard first-line therapy consists
`of metformin in combination with lifestyle modifications.3
`However, ongoing intensification is usually necessary to
`achieve blood glucose control, and the American Diabetes
`Association/European Association for the Study of Diabetes3
`advocate the introduction of insulin as second-line therapy or
`third-line therapy after metformin plus sulfonylurea, with
`further insulin intensification, as needed, to maintain Ale
`within an acceptable range (i.e.,< 7.0%). The Centers for Dis(cid:173)
`ease Control and Prevention estimated that, in the United
`States in 2007, 15.1 % of patients with diabetes (any type) were
`using insulin alone, 11.5% were using insulin in combination
`with oral medications, and 50.6% were using oral medications,
`while the remainder were not using any treatment.4
`Many approaches to insulin administration have been in(cid:173)
`vestigated in order to circumvent the common fear of injec(cid:173)
`tion, such as oral and inhaled insulin, in addition to needle-free
`
`devices. However, injectable insulin is the mainstay approach
`and can be administered in three ways: vial and syringe, in(cid:173)
`sulin pen devices, and insulin pump.
`Since the first insulin pen was introduced in 1985, insulin
`pens have significantly influenced the treatment of diabetes.
`Other articles in this supplement will provide an overview of
`the options available in terms of insulin administration and
`the advantages and disadvantages of each approach. There(cid:173)
`fore, this information will not be repeated here. In brief, in(cid:173)
`sulin pens offer several advantages over the vial and syringe
`method, such as discretion of use, portability, reduced dose
`variability, and reduced risk of hypoglycemia. 5
`8 The reluc(cid:173)
`-
`tance of patients to initiate insulin therapy in a timely manner
`is an important factor to consider when developing new
`methods of insulin administration to address the common
`concerns regarding insulin therapy, such as social embar(cid:173)
`rassment or stigma and needle anxiety. 9
`These concerns, as well as constant improvements in ex(cid:173)
`isting technologies, have led to important developments in
`insulin pen technology. 5
`10 Some of the targets include ease of
`'
`use and training, injection force, differentiating features, dose
`accuracy, maximum dose per injection, memory of the dose,
`and easier cartridge change, as well as improvements
`in needle technology with smaller /narrower needles and
`
`sanofi-aventis, Paris, France.
`
`S-79
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`PERFETTI
`
`improved flow in the needle, which are covered in detail in
`other reviews.11-16 These developments are especially im(cid:173)
`portant when considering that, overall, the use of pens for
`insulin administration, particularly in the disposable form, is
`.
`.
`5
`mcreasmg.
`There are geographical variations in the methods used for
`injecting insulin worldwide (Fig. 1). 17 The first aim of this
`review is to investigate potential reasons for these differences.
`As hospitalization is frequent for patients with diabetes and
`because, in some cases, it is an opportunity to initiate insulin
`in patients with type 2 diabetes with suboptimal glycemic
`control, the different methods of insulin administration
`within an inpatient setting should also be examined.
`
`Global Patterns of Insulin Pen Use
`
`Worldwide, insulin pens are used by just over 60% of in(cid:173)
`sulin users; there are, however, marked differences between
`regions (Fig. 1 ). 17 For example, in Japan, China, and Australia,
`approximately 95% of patients on insulin use insulin pens
`rather than other methods (e.g., vial and syringe or insulin
`pump). 17 In contrast, insulin pens are only used by approxi(cid:173)
`mately 20% of insulin users in the United States and India. 17
`Furthermore, there are substantial differences in the use of
`reusable and disposable insulin pens among patients taking
`insulin. In France, Italy, Spain, Sweden, Turkey, Japan, and
`China, patients use a greater percentage of disposable pens.
`Patients taking insulin in Brazil, Canada, China, Germany,
`India, The Netherlands, and Poland use a greater percentage
`of reusable pens, whereas patients in Australia and the United
`Kingdom use reusable and disposable pens almost equally
`(Fig. 1). 17
`
`Most insulin pens are dedicated to specific types of insulin
`and are therefore manufacturer- and product-specific. In
`terms of insulin analogs, SoloSTAR® and ClikSTAR® (both
`sanofi-aventis, Paris, France) are used for administration of
`insulin glargine and insulin glulisine, FlexPen® and Novo(cid:173)
`Pen® 4 (Novo Nordisk, Bagsv<£rd, Denmark) are used for
`administration of insulin detemir, insulin aspart, and pre(cid:173)
`mixed insulin aspart, and the Luxura® pen and KwikPen™
`and Humalog® prefilled pens (Eli Lilly and Co., Indianapolis,
`IN) (hereafter, the Humalog prefilled pen, also known as the
`"original prefilled pen," is referred to as the Lilly prefilled pen)
`are available for insulin lispro and premixed insulin lispro
`formulations. Several insulin devices are also produced by
`third parties, such as Becton-Dickinson and Co. (Franklin
`Lakes, NJ), Owen Mumford (Woodstock, UK), and Ypsomed
`(Burgdorf, Switzerland). Many of these pens are also available
`in disposable form or can be fitted with cartridges to deliver
`manufacturer-specific human/neutral protamine Hagedorn
`(NPH) insulin-based products.
`Although the restrictions relating to manufacturer and
`product specificity may affect the variations in pen use ob(cid:173)
`served between regions, other factors, such as access to
`funding, local treatment guidelines, physician awareness, and
`patient preference, must also be considered.
`
`Clinical Factors
`
`Access
`
`Perhaps one of the most important drivers for the use of a
`specific product by patients is the funding status and whether
`the product is reimbursed by the local/national health service
`
`"C
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`
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`
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`
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`
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`
`30
`
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`■ Vial
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`FIG. 1. Geographical variations in the use of pens versus vial and syringe to administer insulin worldwide (as of June 2009).
`Data are percentages of patients using reusable cartridge pens, disposable pens, and insulin vials. Data source: IMS Health.17
`
`Country
`
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`

`

`INSULIN PEN USE
`
`S-81
`
`or by a medical insurance scheme. In the United States, for
`example, reliance on medical insurance means that patients
`are dependent on the products approved for funding by the
`insurance provider. However, many insurance providers
`currently have a limited list of approved products. Similarly,
`for those individuals without health insurance who rely on
`Medicaid, a further reduced list of approved products may
`apply. Modern insulin analogs and their respective devices
`are widely available on the approved lists, but overall access
`for insulin administration with pens is lower than for the vial
`and syringe. Therefore, many patients may use the vial and
`syringe to inject their insulin regimen, and others have access
`only to early-era insulin such as NPH insulin and human
`insulin.
`Thus, many insulin users in the United States and in other
`countries are unable to reap the benefits of pairing the most
`modern insulin analogs with devices that have been designed
`and engineered to facilitate their injection. It is important to
`try to change this situation. Recently published data have
`shown that using pen devices is cost-effective because it re(cid:173)
`duces the overall cost of the management of diabetes com(cid:173)
`pared with syringe and needles. In a study of U.S. patient
`records,8 switching from the vial and syringe to insulin pens
`was associated with improved medication adherence and
`reduced the all-cause annual treatment costs by $1,590 per
`patient (from $16,359 to $14,769; P < 0.01) after taking into
`account the greater device costs associated with insulin pens
`versus the vial and syringe. These lower costs were mainly
`the result of reduced healthcare costs attributable to hypo(cid:173)
`glycemia ($1,415 vs. $627; P < 0.01). This significant decrease
`was reflected in significant annualized mean savings, par(cid:173)
`ticularly for hospitalization ($857 vs. $288; P < 0.01) and
`pharmacy ($254 vs. $176; P < 0.01) costs. 8 Decreases in costs
`of emergency visits and hospitalizations associated with
`hypoglycemia were largely driven by decreases in the mean
`annual number of emergency room visits and hospital length
`of stay.
`A retrospective analysis of patients with type 2 diabetes on
`a Medicaid program in North Carolina18 showed that those
`who switched from oral antidiabetes agents to an insulin pen
`incurred significantly reduced total annualized healthcare
`costs compared with those who switched from oral anti(cid:173)
`diabetes agents to vial and syringe ($14,857.42 vs. $31,764.78,
`respectively; P < 0.05). These reduced costs were attributable
`to lower hospital costs ($1,195.93 vs. $4,965.31, respectively;
`P < 0.05),
`reduced diabetes-related costs
`($7,324.37 vs.
`$13,762.21, respectively; P < 0.05), and reduced outpatient
`costs ($7,795.98 vs. $13,103.51, respectively; P < 0.05).
`In the same study,18 total healthcare costs, excluding pre(cid:173)
`scriptions for oral antidiabetes agents, insulin, or devices,
`were comparable for patients who switched from a syringe to
`a pen device (n = 560) ($11,476.42) and for those who re(cid:173)
`mained on syringe therapy (n = 560) ($10,755.31). A cost re(cid:173)
`duction was observed in syringe-related resource use after
`switching to a pen (from $670.52 to $535.70). The overall
`medication adherence
`rate was significantly higher(cid:173)
`although numerically only slightly higher-for patients who
`switched from syringe to pen than for those who remained on
`syringe therapy (92% vs. 90%, respectively; P < 0.05). How(cid:173)
`ever, the diabetes-related medication adherence rate for pa(cid:173)
`tients who switched from syringe to pen was significantly
`lower than for those who remained on syringe therapy (45%
`
`vs. 56%, respectively; P < 0.05). Unfortunately, the authors
`did not identify or speculate on the reasons associated with
`lower adherence in patients who switched from syringe to
`pen devices. Added treatment costs could be one of the rea(cid:173)
`sons for this observation. Alternatively, a change in insulin
`regimen could account for some of the differences; because
`NovoPen and FlexPen were the only pen devices included in
`this study, any changes to an insulin produced by a company
`other than Novo Nordisk were not considered in the analysis.
`Based on these findings, the use of an insulin pen can re(cid:173)
`duce total treatment costs and should be more actively con(cid:173)
`sidered for reimbursement by health insurance schemes.
`Actual annual savings may range from $1,600 to $15,000.
`
`Local treatment guidelines and insulin availability
`
`A factor related to patient access is local clinical guidance.
`For example, in the United Kingdom, the National Institute
`for Health and Clinical Excellence (NICE) develops its own
`recommendations, not only for a disease setting but also for
`specific treatments. In the NICE updated CG87 guidelines
`(available since May 2009) covering newer agents for type 2
`diabetes, 19 NICE recommends adding insulin when control
`of blood glucose remains or becomes inadequate (HbA1c
`:;:,
`7.5% or other higher level agreed with the individual) with
`other measures. Thus, insulin is likely to have been underused
`in the United Kingdom as a result of previous guidelines.
`However, the new guidelines advocate its use for the treatment
`of type 2 diabetes and provide evidence to suggest that the
`new insulin analogs offer advantages over NPH insulin in
`terms of reduced rates of hypoglycemia. Following the publi(cid:173)
`cation of these new guidelines, the use of insulin analogs is ex(cid:173)
`pected to increase, which may also increase the use of pen devices.
`Meanwhile, in Germany, there is no such support in terms
`of treatment guidelines for the use of insulin analogs.20 As a
`consequence, a lower use of pen devices may be anticipated.
`However, as shown in Figure 1, pen devices, particularly
`reusable/ cartridge pens, are more commonly used in Germany
`than the vial and syringe.
`
`Physician Awareness
`A survey of primary care physicians and endocrinologists21
`in the United States indicates that the physicians' preferences
`in terms of pen use were a function of their personal and
`practice characteristics, as well as their perceptions of the
`pens themselves. Physician characteristics (specialty, thera(cid:173)
`peutic philosophy, and practices) play an important role in
`their decision regarding which treatment to give to their pa(cid:173)
`tients. The presentation of pens as an option to patients, by
`physicians, is strongly associated with perceived pen conve(cid:173)
`nience and ease of use. However, physicians' pen recommen(cid:173)
`dations and the estimated pen use/ initiation of pen use by their
`patients are most strongly associated with the perception that
`pen use is better at facilitating self-care and blood glucose
`monitoring.
`A survey of residents from Ontario, Canada, 66 years of age
`or older, who received a first prescription for insulin between
`1998 and 2006 indicated that the proportion of patients using
`insulin pen devices increased from 46% in 1998 to 86% in
`2006.22 Patients who started insulin under the guidance of a
`specialist were statistically more likely to use an insulin
`pen (odds ratio [OR], 2.24; 95% confidence interval [CI],
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`S-82
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`PERFETTI
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`2.08-2.40), which suggests that specialists are more aware of
`the advantages of insulin pens. Patients who started insulin in
`long-term care residences, where staff are more likely to ad(cid:173)
`minister insulin than patients, were less likely to use an in(cid:173)
`sulin pen (OR, 0.51; 95% CI, 0.49-0.54). Initiation of insulin
`during hospitalization was also less likely to be with an
`insulin pen (OR, 0.74; 95% CI, 0.71-0.78).22
`Collectively, these surveys indicate profound variations in
`physician awareness of the advantages of insulin pens versus
`the vial and syringe, particularly for populations who may
`benefit most from these advantages. Another factor that
`should be considered is that the preference for using insulin
`pens rather than a vial and syringe may also be driven by the
`nursing staff and certified diabetes educators who are usually
`involved in delivering patient training. In one survey23 of 112
`pediatric diabetes specialist nurses across the United Kingdom,
`the patient's doctor was more commonly responsible for
`selecting the diabetes regimen (always, 20.5%; sometimes,
`59%; never, 20.5%) than the pediatric diabetes nurse (always,
`9%; sometimes, 67%; never, 24%); the patient's age was
`considered the most important criterion (always, 57%;
`sometimes, 31 %; never, 12%). Similarly, the final decision on
`starting dose was more frequently made by the doctor than
`the diabetes nurse (25% vs. 9%). Interestingly, reusable pens
`were more commonly prescribed in this patient population
`than either disposable pens or syringe (86% vs. 27% vs. 17%),
`whereas pumps were not used as initial therapy. Similar
`findings were reported in a related survey24 for patients with
`type 2 diabetes in the United Kingdom, which reported that
`the consultant physicians had the greatest influence for most
`decision-making, while nursing groups held varying per(cid:173)
`ceptions of who made clinical decisions. Unfortunately, the
`findings of these two surveys may not be representative of
`other countries.
`An additional aspect that should be taken into account is
`nurses' perception of insulin pens because of their role in
`treatment administration. To our knowledge, one study has
`assessed nurse satisfaction using insulin pens. That study
`surveyed 54 registered nurses in a community hospital after
`implementation of insulin pen devices. 6 Overall, the study
`reported that nurses believed that insulin pens were more
`convenient, simple, and easy to use and provided an overall
`improvement compared with conventional vials/syringes.
`Clearly, this is an area that warrants further research to
`determine how involved nurse practitioners and certified di(cid:173)
`abetes educators are in guiding the treatment of diabetes.
`
`Patient Factors
`
`Although access to treatment is an important factor, patient
`factors, such as patient preference, should also be considered.
`Some patients may prefer one method of administration over
`another; notably, studies have demonstrated patient prefer(cid:173)
`ence for insulin pens versus the vial and syringe.25
`27 More(cid:173)
`-
`over, it seems feasible that cultural factors, such as the
`decision to use sustainable technologies, may also influence
`the patient's decision to use a specific device, although this
`has yet to be formally evaluated.
`In a study conducted in Australia, 2,674 patients with di(cid:173)
`abetes who were provided with LANTUS® (insulin glargine;
`sanofi-aventis) SoloSTAR as part of their routine clinical
`practice participated in a telephone survey after 6-10 weeks of
`
`use to report their feedback and acceptance. At interview,
`96.8% of participants were still using the SoloST AR, and the
`majority (95.4%) reported that they were satisfied or very
`satisfied with using the device.28 This was consistent with
`findings reported by the healthcare practitioners involved in
`the study.29 However, the distinction between the preference
`for reusable and disposable insulin pens seems less clear.
`Therefore, using a reusable or disposable pen may reflect a
`combination of patient preference, devices available for specific
`insulin formulations, differences in costs, physician preference,
`and local availability of specific devices. Unfortunately, no
`study has yet investigated the reasons for the geographical
`differences in the use of reusable versus disposable pens.
`From a patient's perspective, switching from the vial and
`syringe to insulin pens was associated with a reduced risk of
`experiencing a hypoglycemic event (OR, 0.50; 95% CI, 0.37-0.68;
`P < 0.05) based on the rates of hypoglycemia recorded during
`the over 6-month pre-index and over 2-year post-index periods. 8
`This in itself should provide a compelling reason to use insulin
`pen devices rather than the vial and syringe. This is supported
`by findings from a recent study30 in which pen device-naive
`patients reported greater preference for the KwikPen and Flex(cid:173)
`Pen compared with the vial and syringe, which was particularly
`true for ease of use and ease of operation.
`Interestingly, patients may prefer the specific pen features
`of one brand of pen versus another. For example, in a study by
`Haak et al., 31 510 people with diabetes from the United States,
`France, Germany, and Japan were provided with three mar(cid:173)
`keted prefilled insulin pens and a prototype pen. The partic(cid:173)
`ipants were asked to rank their pens based on order of
`preference and then to rank their preferred features. In this
`study, significantly more participants expressed overall
`preference for SoloSTAR (53%) versus FlexPen (31 %) and the
`Lilly prefilled pen (15%) (P < 0.05), and there were significant
`differences in terms of specific pen features. Of note is that
`more people preferred the reduced effort required to inject
`40 U, ease of setting the dose, and ease/intuitiveness of using
`SoloSTAR versus the other pens, whereas the Lilly prefilled
`pen was preferred for the distance at which the dose button
`sticks out for 40 U and how well the cap fits the pen. Mean(cid:173)
`while, in a study by Ignaut et al., 3° KwikPen and FlexPen were
`preferred over the vial and syringe by pen-naive patients, but
`the KwikPen was significantly preferred over the FlexPen,
`suggesting that the KwikPen may be easier to use than the
`Lilly prefilled pen. As yet, no studies have compared Kwik(cid:173)
`Pen with SoloST AR.
`In terms of reusable pens, a study of 654 patients with di(cid:173)
`abetes from the United States, Canada, the United Kingdom,
`France, and Germany assessed the performance of ClikSTAR
`compared with NovoPen 3, NovoPen 4, and Luxura. 32 For
`each pen type, a face-to-face questionnaire assessed the fol(cid:173)
`lowing features: fixing and replacing the cartridge, hearing
`and feeling the clicks, dialing and delivering a 40-U dose, and
`overall usability. In this study, ease of use and overall per(cid:173)
`formance of ClikSTAR were equal to or better than those of
`NovoPen 3, NovoPen 4, and Luxura (Table 1).
`It must be acknowledged that insulin pens may not be
`suitable for all patients. In particular, a large number of
`overweight and obese patients with type 2 diabetes are still
`likely to have insulin requirements exceeding the greatest
`dose per injection of the current insulin pens. For individu(cid:173)
`als who regularly inject more than 80 U per dose, a pen or
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`INSULIN PEN USE
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`TABLE 1. EASE OF UsE AND EASE OF COMPLETING TASKS Us1NG CuKSTAR, NovoPEN 3, NovoPEN 4,
`AND LUXURA INSULIN PENS
`
`Luxura
`
`NovoPen 3
`
`NovoPen 4
`
`ClikSTAR
`
`Overall score (%)
`Ease of use
`Ease of completing taska
`Ease of useb
`Cartridge replacement
`Hearing/ feeling clicks
`Overall rating
`Difficulty completing taskc
`Dialing 40U
`Delivering 40 U
`Fixing cartridge
`Safety
`
`79
`
`5.7*
`6.0*
`6.0* /5.5
`3.4*
`
`1.1
`1.2'1
`1.2
`1.2
`
`50
`
`4.5
`4.6
`5.7 /5.5
`2.6
`
`1.3§
`1.2'1
`1.6-;-
`1.3§
`
`83
`
`5.7*
`5.9*
`6.0*/~.8'
`3.6'
`
`1.3§
`1.1
`1.4§
`1.3§
`
`86
`
`6.1°"
`6.i·
`6.1*/~.97
`3.7'
`
`1.1
`1.1
`1.2
`1.2
`
`Reproduced with permission from Penfornis. 32
`"On a scale of 1-7, where 1 =not at all easy and 7 = extremely easy.
`6Percentage of patients rating pens as good/very good/excellent.
`con a scale of 1-5, where 1 = no difficulty and 5 = got stuck.
`*P =0.05 versus NovoPen 3; -r-p = 0.05 versus all pens; Ip= 0.05 versus NovoPen 3 and Luxura; §p= 0.05 versus ClikSTAR and Lilly Luxura;
`11 P=0.05 versus ClikSTAR and NovoPen 4.
`
`cartridge containing 300 U can only be used for three full in(cid:173)
`jections; the subsequent dose would need to be split with a
`second pen or cartridge. Clearly, this also has cost and wast(cid:173)
`age implications, such that disposable pens should be avoided
`in these patients. For these patients, although split-dose in(cid:173)
`jections are possible, the use of a vial and syringe may be more
`appropriate because vials are available with greater volumes
`(e.g., 10 mL, 1,000 U) or in greater concentrations (e.g., 300 or
`500U/mL).
`To date, except for the studies described above, we are
`unaware of any others that have included more than 100-200
`subjects, and no study has included all six of these pens or
`other third-party devices. Meanwhile, almost all of the studies
`published to date have been sponsored or conducted by the
`manufacturers of the pen devices, raising the potential for bias
`35
`towards their own pens. Of note is that several studies33
`-
`have only compared the patient preference and ease of use of
`two devices, commonly a prefilled pen and a reusable pen.
`Consistently, these studies showed greater preference and
`greater ease of use for the prefilled pen than the reusable pen.
`However, this is unsurprising because prefilled pens do not
`require cartridge insertion, a step that may be considered
`quite complex without adequate training.
`It seems that larger independent studies with a represen(cid:173)
`tative population of patients with type 1 and type 2 diabetes
`and with a greater range of devices will be needed to gain
`further insight into the preferred features of each device and
`the suitability of each pen for specific patient populations,
`such as children and elderly patients.
`Taken together, on insulin initiation, the patient should be
`given an opportunity to evaluate the devices for each insulin.
`Indeed, patients may find a specific device to be easier to use,
`which should be considered in the final decision on which
`insulin should be used.
`
`Inpatient Insulin Use
`
`Inpatient insulin use is a commonly overlooked aspect of
`clinical care. Insulin is often administered as part of overall
`
`patient care, particularly in patients undergoing surgery, to
`manage blood glucose levels, thus avoiding unnecessary hy(cid:173)
`perglycemia. The use of insulin pens has been reported to
`extend to the inpatient setting, which may be the result of the
`increasing use of basal-bolus regimens instead of the more
`traditional sliding-scale approach. Accordingly, within a
`clinical setting, patients may require different types of insulin,
`and approaches that simplify insulin treatment appear to be
`well received. As previously described, a study evaluating
`nurse satisfaction with insulin pens versus the vial and sy(cid:173)
`ringe within an inpatient setting demonstrated that the nurses
`believed insulin pens to be more convenient, simple, and easy
`to use than the vial and syringe.6 Patients often continue in(cid:173)
`sulin therapy in the outpatient setting; therefore, patient
`preference and treatment costs are factors that should also be
`considered when using insulin pen devices in this setting.
`Davis et al. 36 undertook a telephone survey of 94 patients
`randomized to receive insulin administered either via a pen
`device (n = 49) or a vial and syringe (n = 45). Patients in the
`pen group who self-injected at least one dose of insulin during
`hospitalization were more likely to use the pen device on
`discharge than those in the vial and syringe group. Further(cid:173)
`more, the authors estimated that using insulin pens during the
`hospital stay was associated with a cost saving of $36 per
`patient (P < 0.05).
`As a result, familiarization of patients with insulin pens
`within an inpatient setting may encourage the use of pens in
`the outpatient setting. This, in tum, could reduce the costs
`incurred as a result of using the device and the need for
`training within an outpatient setting. However, prospective
`studies are needed to investigate these factors.
`Insulin pens carry several disadvantages that are appro(cid:173)
`priate in an inpatient setting, similar to an outpatient setting,
`for example, incorrect insulin administration, the risk of
`needlestick injury,37 and the potential risk of infection if in(cid:173)
`sulin pens are used against Food and Drug Administration
`recommendations and shared between patients.38 However,
`these factors are also evident for the vial and syringe and other
`injectable drugs, and the use of safety needles should reduce
`
`Sanofi Exhibit 2140.005
`Mylan v. Sanofi
`IPR2018-01676
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`

`S-84
`
`PERFETTI
`
`the risk of needlestick injury. Furthermore, insulin pens gen(cid:173)
`erally offer greater differentiation features, including color
`7
`features on the label and dose button, 5
`10 for example, which
`,
`,
`could reduce the risk of errors. On the other hand, the nurses
`using insulin pens may need more training on how to use the
`devices, particularly if several different pens with slightly
`different usage instructions are used within the same clinic.
`We found very few studies that investigated the effect of
`specific devices within an inpatient setting, particularly
`compared with other devices such as insulin pumps(cid:173)
`although pumps have limited indications in this setting.
`Clearly, further studies are needed to confirm the advantages
`and disadvantages of using insulin pen devices within an
`inpatient setting and the effects of inpatient use of insulin pens
`on the continued use of insulin pens on discharge.
`
`Conclusions
`
`In this review we have discussed how pen use varies
`greatly among geographical regions. It seems that one of the
`main reasons for this variation is access to the devices, whe(cid:173)
`ther this is through guidelines produced by national clinical
`bodies or through approval of the use of products by insur(cid:173)
`ance providers and local health services, despite analyses of
`healthcare costs of patients using pen devices suggesting
`potential cost savings compared with the vial and syringe.
`Patients consistently report a preference for insulin devices, as
`such devices improve the accuracy and convenience of insulin
`administration, but the lack of physician awareness of the
`benefits of pens, particularly among primary care providers,
`also seems to limit the uptake of insulin devices. International
`surveys of patients and healthcare providers may better re(cid:173)
`veal the factors underlying the uptake of insulin pen devices
`for the treatment of diabetes. However, the choice of insulin
`administration method must ultimately be based on indi(cid:173)
`vidualized patient care as in certain patient groups insulin
`pens may offer fewer advantages than in others.
`In terms of inpatient use, there is evidence supporting the
`use of intensive insulin regimens, rather than the traditional
`sliding-scale regimen. However, few studies have addressed
`the impact of insulin pen devices in this setting, and further
`studies are clearly needed to evaluate whether insulin pen
`devices are associated with improved clinical outcomes, ad(cid:173)
`herence, and quality of life.
`
`Acknowledgments
`
`This review was sponsored by sanofi-aventis. Editorial
`support was provided by the Global Publications group of
`sanofi-aventis.
`
`Author Disclosure Statement
`
`R.P. is an employee of sanofi-aventis.
`
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