Table 3.
Prefilled insulin injectors.
| Study, year | Device studied/device compared | Participants | Study design | Outcomes |
|---|---|---|---|---|
| Korytkowski et al., 2003 (89) |
FlexPen® vs. vial and syringe | 121 adults aged 28–81 years with T1DM and T2DM | 8-week multicenter, randomized, open-label, comparative, two-period crossover trial. During the 4-week run-in period, the patients continued the therapy with the previous devices (i.e., their own pens or syringes), to administer a mixture of 70% aspart protamine suspension and 30% aspart insulin. Insulin doses were optimized. Then patients were randomly allocated to one of the study groups. Half of the participants started the trial using prefilled, disposable pens for 4 weeks, and next they were crossed over to a vial/syringe group for another 4 weeks. The second group followed the study in the reverse order. Patients’ preference was assessed based on the Patient Preference Questionnaire in the final visit of the second treatment period. |
103 patients completed the study. Most of the patients (78%) preferred the pen over vial and syringe methods, and 85% found the FlexPen® more discreet in public. Ease of pen use was greater for 74% of respondents, and 85% of them considered the insulin dose scale much easier to read in the pen injector. However, metabolic control was comparable in both FlexPen® and vial and syringe group and patients’ HbA1c improved during the study (p < 0.05). |
| Niskanen et al., 2004 (100) | FlexPen® vs. Humalog® Pen | 137 patients (mean aged 62.3 ± 9.2 years) with T2DM | 24-week randomized, multinational, multicenter, open-label, 2-period crossover trial. After a 2-week run-in period, patients were randomly involved into a 12-week treatment period with BIAsp 30 (30% of soluble insulin aspart and 70% protaminated insulin aspart) or Mix25 (25% soluble insulin lispro and 75% neutral protamine lispro) using FlexPen® or Humalog® Pen. Next, participants were crossed over to the second treatment period with another type of insulin and pen device. In the final questionnaire, patients’ preference for the pen injectors was assessed. |
FlexPen® received the highest rates for all device features assessed in the final questionnaires (all p < 0.005). 32.4% of patients experienced problems with Humalog® Pen when only 9.0% with FlexPen® (p < 0.001). 74.6% of respondents preferred to continue using FlexPen® (in comparison with 14.3% preferred Humalog® Pen, p < 0.001). |
| Haak et al., 2007 (101) | SoloSTAR®, Humalog®/Humulin pen, FlexPen®, and prototype Pen X | 510 patients aged 11–82 years (232 adults with T2DM receiving only OHAs and 278 insulin users with T1DM or T2DM). | Multicenter, observational study The trial consisted of 1-hour face-to-face interviews aimed at evaluating the usability of the devices and patients’ preferences. Firstly, participants were asked to prepare the device and deliver a 40-unit dose relying on their intuition and/or relevant manuals. Any training and maintenance was not provided. Next, respondents evaluated abovementioned procedures for each pen in a five-point scale (1 = poor, 5 = excellent). |
Significant majority of patients prepared the SoloSTAR® properly and performed a correct injection with the device in comparison with the other pens (p < 0.05). Moreover, most of the patients (53%) preferred to use SoloSTAR® than Flex Pen® (31%) and Humalog®/Humulin pen (15%). |
| Ignaut et al., 2008 (87) | FlexPen® (NovoLog® Mix 70/30) vs. KwikPen® (Humalog® Mix75/25) | 50 insulin pen device (25 FlexPen®s and 25 KwikPen®s) | In this study, ergonomic features, injection force (as glide force (GF), and glide force variability (GFV)) were measured and compared in FlexPen® and KwikPen® injectors. | FlexPen® was lighter than KwikPen® and had a smaller diameter at the cartridge holder and dose window while KwikPen® presented a shorter overall pen length with a shorter thumb reach at both 30- and 60-unit dose settings. For both the 30-unit and 60-unit doses, maximum GF was lower in KwikPen® than in FlexPen® (3.42 vs. 5.36 lb and 3.61 vs. 5.62, respectively, both p < 0.0001). |
| Asakura et al., 2009 (93) | FlexPen® vs. vial and syringe | 60 HCPs (30 insulin experienced and 30 insulin-naïve ones) | Multicenter, observational study The first part of the study consisted of insulin delivery training among insulin-naïve participants. Next, respondents were randomized into 2 study groups, one of group performed an injection of 10 U with FlexPen® (Day 1) and then with vial/syringe (Day 2). The second group followed the tasks in the reverse order. Subsequently, insulin-naïve HCPs assessed the devices and made an overall comparison in the evaluating questionnaires (rate range: 1 = very poor, 5 = excellent). The second part of the trial depended on the randomized, accuracy testing of the two devices (FlexPen® and vial/syringe) by 30 insulin-experienced and 20 insulin-naïve HCPs. After injecting 10 U of insulin, devices were weighed and the outcomes were converted into insulin units (0.1 g = 10 U). |
Insulin therapy-naïve HCPs preferred FlexPen® and found it much easier to handle than vial and syringe (p < 0.001). Moreover, the pen was more accurate than syringe when used by both insulin experienced and non-experienced HCPs (p < 0.001). |
| Asakura et Jensen, 2009 (102) | FlexPen® vs. OptiClik® | 61 adults (mean aged 61.9 ± 12.3 years) with T2DM | Randomized, open-label, crossover study. All study groups were insulin-device-naïve. Participants were randomized into intuitiveness and instruction time group and then randomized again to the subgroups starting injections with FlexPen® or OptiClik®. The intuitiveness group had to make an injection into a cushion without any training or manual. At the end the study, the group completed a intuitiveness and device understanding questionnaire. The second group received an instruction before injecting a dose. Both groups completed the important features of the device questionnaire. Afterward, everyone received the injectors again and became instructed how to use each pen. In the end, patients fulfilled questionnaires regarding ease of use and overall preference. |
FlexPen® required less instruction time and was more intuitive for most of patients (p < 0.001). None in the instruction time group considered FlexPen® difficult to learn, but 45% of the group found OptiClik® difficult/very difficult to learn. Moreover, respondents rated FlexPen® (in comparison to OptiClik®) as simpler to use (77% vs. 12%, p < 0.001), easier to inject (67% vs. 13%, p < 0.001), and more convenient 71% vs. 12%, p < 0.001). Analogically, most of the respondents preferred using FlexPen® than OptiClik® (82% vs. 13%, p < 0.001). |
| Ignaut et al., 2009 (90) | KwikPen® vs. vials and syringes and KwikPen® vs. FlexPen® | 232 adults (aged 40–75 years) with T1DM or T2DM | 1-day, open-label, randomized, crossover study. The study assessed the preference of using KwikPen® vs. vial/syringe and next, KwikPen® vs. FlexPen® among insulin users. Dose accuracy, ease of use (via insulin device assessment battery), and respondents’ preference (via insulin device preference battery) for each pen were examined, and both pens were evaluated with the final preference questionnaire. |
KwikPen® was the most preferable device (over both vial and syringe and FlexPen®) because of its appearance, quality, discretion, convenience, public use, ease of learn and use, reliability, dose confidence, and following insulin regimen. KwikPen® was considered as overall the most satisfying device, willingly recommended to others. |
| Yakushiji et al., 2010 (103) | OptiClik®, SoloSTAR®, MirioPen, and FlexPen® | 22 (50% male, 50% female) respondents (11 experienced and 11 non-experienced with insulin injectors) aged 25–57 years. | Observational study Non-experienced participants were educated how to use the injectors. All the respondents made 2 injections with 5 examined devices. The first one was a self-injection in the prosthetic skin attached in the respondents’ flank. The second injection was made to the prosthetic skin placed in the upper arm of the mock patient (other injection). Every injection contained 10 units of saline. In the end, both self- and other injections with every device were evaluated in the questionnaire and rated from 1 to 5. |
FlexPen® was rated as the best device for self-injections. However, FlexPen® was also selected the worst one for the other-injections because it was too long, was less stable, and had inadequate visibility of the dial. OptiClik® was evaluated as the best device for other injection but the second worst one to self-injection. |
| Bailey et al., 2011 (104) | FlexTouch® vs. KwikPen® | 160 participants: 79 patients with T1DM or T2DM and 81 HCPs (40 physicians, 41 nurses) | 1-day, randomized, crossover study. Respondents were randomly assigned to one of the groups (starting the study with FlexTouch® or KwikPen®) and then crossover to test the second pen. Participants were trained how to use the devices before the test injections. Next, both patients and HCPs made multiple injections (with randomly altered doses including 20, 40, and 60 U) into a foam cushion and answered questions concerning ease of use, confidence, and preferences. |
FlexTouch® (compared to KwikPen®) was rated as most preferred device (86% vs. 7%; p < 0.001), easier to use (85% vs. 4%; p < 0.001), and recommended to others (88% vs. 6%; p < 0.001). Additionally, FlexTouch® was characterized as the better device in the injections for ease of depressing the push button and ease of injecting the doses (p < 0.001 for all). FlexTouch® was found as the most confident in correcting and completing insulin delivery (73% vs. 6%; p < 0.001). |
| Hancu et al., 2011 (105) | SoloSTAR® | 6481 adults (mean aged 54 years) with T1DM or T2DM | 6- to 8-week, multinational, multicenter, open, prospective, observational product/device registry study. At the first, registry visit participants were included to the insulin therapy with the new pens (LANTUS SoloSTAR® and/or Apidra SoloSTAR®) and completed a questionnaire regarding their previous experience with insulin injectors (if applicable). Last visit (after 6–8 weeks of SoloSTAR® use) purposed to assess the acceptance of the new disposable pen and compare patients’ experience with the ones used prior the trial. Moreover, series of questions have been asked to evaluate the study period. |
6,364 participants were included to the analysis of patient satisfaction. 77.1% patients had used insulin before inclusion in the study. In the trial, SoloSTAR® was used to administer glargine (97.3%) and/or glulisine (36%) insulin. Most of patients found the new disposable injector as “excellent/good” in learning to use (98.3%), ease of use (97.9%), selecting the dose (97.6%), and reading the dose (95.1%). SoloSTAR® was “much easier/easier” for over 80% of the study group (in comparison with previously used pens) because of ease of use (88.4%) and injecting a dose (84.5%). Furthermore, 98% patients desired to continue using SoloSTAR® in the future. |
| Oyer et al., 2011 (106) | FlexTouch® vs. SoloSTAR® | 120 participants: - 59 patients with T1DM or T2DM -61 HCPs (30 physicians, 31 nurses) |
1-day multicenter, open-label, randomized, crossover study. Respondents were randomly assigned into the study groups (starting test with FlexTouch® or SoloSTAR®). Participants were instructed how to use the pen and performed test injections into a foam cushion, dosing 20, 40, and 80 U. In the following step, both study groups were crossed over to test another pen device. Each pen device was assessed separately (in a form evaluating handling and operation of the pen). Moreover, in the final questionnaire respondents completed regarding their preferences. |
A significant majority of participants (88%) preferred FlexTouch® over SoloSTAR® (10%). They considered FlexTouch® (vs. SoloSTAR®) easier to use (83% vs. 9%), willingly recommended to others (83% vs. 8%; p < 0.001), very/fairly easy to reach the push-button and inject the doses (p < 0.001 for all), more confident in correct insulin delivery (76% vs. 6%; p < 0.001), and managing daily injections (88% vs. 58%). |
| Buysman et al., 2011 (17) | FlexPen® (Levemir) vs. vials (NPH) | 1,876 patients with T2DM (1082 Levemir FlexPen® users and 794 NPH vial ones) | Retrospective analysis from a large geographically diverse US health insurance plan. Patients were divided into 2 study groups—initiating basal insulin therapy with Levemir FlexPen® or NPH in vials. Patients were defined as adherent to therapy if their medication possession ratio (MPR) was at least 80% in the 12-month follow-up period. Patients’ persistence was defined as the lack of gaps in insulin therapy during the follow-up period. |
Patients beginning therapy with Levemir FlexPen® had 39% higher adjusted odds of achieving an MPR ≥80% in comparison to patients with NPH vials (OR 1.39, 95% Cl: 0.55–0.70). Moreover, analysis of persistence presented that patients initiating Levemir FlexPen® had a 38% lower hazard of discontinuation compared to NPH vial users (HR 0.62, 95% CI: 0.55–0.70) |
| Campos et al., 2012 (91) | FlexTouch® vs. vial and syringe | 120 participants: - 60 patients with T1DM or T2DM, - 60 HCPs (30 physicians, 30 nurses) |
1-day randomized, multicenter, open-label, crossover study. Participants were trained how to use the devices. Next, test injections into foam cushion (dosing 20, 55, and 80 U) were made with both vial and syringe and FlexTouch®. Then, respondents separately rated the devices in respect of ease and confidence of use. |
FlexTouch® (compared to vial and syringe) was found a preferred device (88% vs. 5%; p < 0.001), easier to use (91% vs. 6%; p < 0.001), and willingly recommended (91% vs. 3%; p < 0.001). Moreover, participants considered FlexTouch® easier to use, more stable during injection, and better in depressing the push-button and reading the dose scale (all p < 0.001). Patients and HCPs using FlexTouch® were also more confident in properly insulin delivery and metabolic control than the ones using vial and syringe (p < 0.001). |
| Lajara et al., 2012 (94) | FlexTouch® vs. vial and syringe | 120 participants: - 30 needle-naïve patients, - 30 vial and syringe-experienced patients, - 30 physicians, - 30 nurses. |
1-day randomized, multicenter, open-label, crossover study. All participants received an instruction on how to use the injection device. Then they were asked to make a test injection into a foam cushion (dosing 20, 55, and 80 U) with FlexTouch® or vial and syringe (in a random order) and answer questions on confidence and ease of use (1 = very difficult/not at all confident; 5 = very easy/very confident). In the next step, respondents followed the abovementioned procedures with another device. Finally, all participants completed a preference questionnaire to evaluate both methods. |
Both HCPs (nurses: 100% vs. 0%; physicians 87% vs. 7%), needle-naïve (83% vs. 7%), and vial- and syringe-experienced (73% vs. 7%) patients preferred FlexTouch® over vial and syringe for ease of teaching. Moreover, the insulin pen was rated as very/fairly easy for depressing the push-button (physicians: 93% vs. 80%; nurses: 97% vs. 80%; vial and syringe-experienced patients: 93% vs. 90% and needle-naïve ones: 100% vs. 77%). |
| Nadeau et al., 2012 (107) | FlexTouch® vs. KwikPen®
(FT vs. KP) and FlexTouch® vs. SoloSTAR® (FT vs. SS) |
FT vs. KP: 160 participants (79 patients with T1DM or T2DM and 81 HCPs) FT vs. SS: 120 participants (59 patients with T1DM or T2DM and 61 HCPs) |
1-day, randomized, crossover study. The study consisted of 2 comparison groups: FT to KP and FT to SS. Participants were randomized to start the trial with FT or another pen device and then were crossed over to test the second injector. All respondents were educated about using the devices. Both patients and HCPs were asked to make multiple injections of different doses with each pen (FT vs. KP study: 20, 40, 60 U; FT vs. SS study: 20, 40, 80 U). In the end, participants answered the questions regarding ease of use, learning and teaching, confidence in use, and preference. |
FlexTouch® was rated as very/fairly easy to inject, particularly in the maximum dose (compared to KP or SS: ≥80% vs. ≤38% and ≤23%) and very/rather confident in the ability to manage daily injections. FT was also considered as easier to teach and learn to use than KP and SS (all p < 0.001) and preferred for learning and teaching (≥39% vs. ≤4% for KP and ≤6% for SS). Most of the patients and HCPs would recommend FT (≥95%) than KP (≤72%) and SS (≤71%). |
| Pfutzner et al., 2012 (108) | InnoLet® vs. FlexTouch® | 90 patients (mean aged 62 ± 8 years) with T1DM or T2DM, with or without impaired dexterity and visual impairment | Patients became stratified into 4 study groups: A—visually impaired with T1DM and impaired dexterity; B—visually impaired with T2DM and impaired dexterity; C—visually impaired with T1DM or T2DM; D—patients without any impairment with T1DM or T2DM. Participants were asked to perform some test injections (dosing 10, 30, and 50 U) and complete a standardized questionnaire assessing the handling of the pen device. The procedure was repeated with a second insulin injector. In the end, patients evaluated the study by completing a comparative questionnaire. | FlexTouch® was preferred in all study groups including 100% of group D (unimpaired patients). Only a few patients with visual/dexterity impairment preferred InnoLet® (group A—13%, group B—3%, group C—14%). |
| Schipper et al., 2012 (109) | FlexTouch® vs. InnoLet® | 90 patients (mean aged 62 ± 8 years) with T1DM or T2DM | Patients were assigned to the study groups in random order. Participants (educated how to use the devices) were asked to perform a mock injections (with 10-, 30-, and 50-U doses) and complete a final 41 item standardized questionnaire to assess the device. Patients rated each pen in a five-point scale (1 = very easy, 5 = very difficult) regarding injection confidence and performance, dose setting, general handling, and others. | FlexTouch® (FT) was found better than InnoLet® (IL) for the injection procedure (FT: 1.2 ± 0.1 vs. IL: 2.1 ± 0.4; p < 0.001), general handling (1.3 ± 0.2 vs. 2.3 ± 0.7; p < 0.001), confidence of dosing (1.4 ± 0.2 vs. 2.1 ± 0.9; non-significant). Dose setting was ranked equally (FT: 1.6 ± 0.3, IL: 1.7 ± 0.4, non-significant). 92.2% of patients would recommend FT (IL only 30.0%). |
| Pfutzner et al., 2013 (92) | FlexTouch® vs. vial and syringe | 120 participants: - 40 patients with T1DM or T2DM, - 20 caregivers (i.e. parents, relatives) - 20 physicians, - 40 nurses/certified diabetes educators |
1-day single-center, randomized, crossover study. Participants (in random order) were asked to perform testing injections into laboratory tubes (doses of 5, 25, 43, and 79 U) with the devices. Dosing accuracy was measured, and patients completed final questionnaires (device assessment questionnaire, patient perception questionnaire). Next, respondents were crossed over to test another device. At the end of the trial, all participants answered the questions in the device preference questionnaire. |
FlexTouch® presented significantly better dosing accuracy when used by all cohorts and at all doses (p < 0.005 for all doses). The pen injector was rated significantly higher than vial and syringe in both device preference questionnaire (93% vs. 2% for vial and syringe; p < 0.001)) and patient perception questionnaire (in all aspects). |
| Pfutzner et al., 2014 (110) | FlexTouch® (U100 and U200) vs. SoloSTAR® | 64 adults with T1DM or T2DM and 64 HCPs (32 physicians, 32 nurses) |
Multicenter, randomized, open-label, crossover study. The study consisted of one visit. Participants were asked to make 4–6 injections into a foam cushion (dosing 2, 20, 40, 80, 120, and 160 units). Next, they were asked to complete a questionnaire to evaluate the device. These procedures were repeated in each of the three analyzed injectors. After the tests, participants answered the final, overall questions. |
Significant majority of participants preferred to use FlexTouch® U100 (93.0%) and U200 (91.4%), even dexterity-impaired and pen-naïve patients in comparison with SoloSTAR® (p < 0.001), respectively. |
| Cheen et al., 2014 (14) | FlexPen® (NovoMix 30) vs. vial and syringe (Mixtard 30) | 955 patients | Retrospective, single-center, longitudinal study. Data were collected from the outpatient clinics database of the largest acute care hospital in Singapore. During 24 months of the observation adherence, compliance (as medication possession ratio - MPR) and persistence were measured, based on electronic medical and pharmacy refill records. |
Mean MPR was comparable in vial/syringe and pen users (83.8% ± 26.9% vs. 86.0% ± 23.2% respectively, p = 0.266). Persistent with therapy was higher among pen users (odds ratio = 1.36; 95% CI, 1.01–1.86) after adjusting for sociodemographic and clinical covariates. |
| Friedrichs et al., 2015 (111) | SoloSTAR® (SS), FlexPen® (FP), KwikPen® (KP), and FlexTouch® (FT 1 and 2) | 20 pen-experienced patients (mean aged 55 ± 14 years) with T1DM or T2DM | Patients were asked to dial up from zero to maximum and next, dial down from maximum to zero with each pen. Dialing up and down was recorded with a video, and the torque of the devices was analyzed. Next, 16 pen-experienced people with T2DM rated the subjective comfort for each insulin injector after dialing up and down again. |
SS was rated as most comfortable in dialing up by 8 and dialing down by 6 of the 16 respondents; analogically, FP was ranked by 5 and 8, respectively; FT1: 2 and 1; KP: 1 and 1. FT2 was evaluated as least comfortable by 12 and 10 patients. Comfort of up- and down-dialing was considered “very comfortable” for SS by 15 patients each and next, FP (12 and 14), KP (10 each), and FT1 (9 and 7). FT2 was ranked “less/not comfortable” by 10 and 11 respondents, respectively. |
| Slabaugh et al., 2015 (16) | Pen vs. vial | 3,172 insulin-naïve patients with T2DM (aged 18–89 years), 1,231 vial users and 1941 pen ones | Retrospective, observational study. The study analyzed data from Medicare Advantage with Prescription Drug insurance database. Patients initiating basal insulin administration with pens vial/syringes were observed. Persistence and adherence (as proportion of days covered—PDC and medication possession ratio—MPR) were measured during the 12-month follow-up period. |
Adjusted mean PDC was significantly higher in the pen cohort than the vial one (0.67 vs. 0.50 respectively, p < 0.001), the same as mean MPR (0.75 vs. 0.57 respectively, p < 0.0001). Adjusted odds for adherence (PDC at least 80%) presented a positive association with insulin pen use (odds ratio = 2.19, 95% CI: 1.86–2.59). The adjusted risk of non-persistence was lower among pen users (hazard ratio = 0.42, 95% CI: 0.38–0.45). |
| Warren et al., 2019 (112) | FlexTouch® (200 U/ml) vs. SoloSTAR® (100 U/ml) | 145 patients with T2DM using ≥ 81 units of insulin a day | 32-week randomized, multicenter, open-label, crossover study. Patients became randomly assigned to one of the study groups and started a treatment with insulin degludec (200 U/ml, 3 ml FlexTouch®) or glargine (100 U/ml, 3 ml SoloSTAR®). After 16 weeks, participants were crossed over to another insulin therapy. Patients’ preference and treatment impact were assessed in the final PRO questionnaires. |
Most of the patients found FlexTouch® “extremely easy” for learning (62.5% vs. 43.0%, p < 0.01), maintaining (63.2% vs. 42.2%), and adjusting a dose (63.2 vs. 44.4%). Moreover, respondents considered FlexTouch® (compared to SoloSTAR®) as very/extremely confident in using the injector (60.3 vs. 36.3%) and its accuracy (50.7% vs. 30.4%). A significant majority of patients preferred therapy with FlexTouch® (59% vs. 22%), would like to continue (67% vs. 15%), and willingly recommend the injector (67% vs. 14%) in comparison with SoloSTAR®. |
T1DM, type 1 diabetes mellitus; T2DM, type 2 diabetes mellitus; HCPs, healthcare professionals; MPR, medical possession ratio; U, units of insulin; SS, SoloSTAR®; FP, FlexPen®; KP, KwikPen®; FT1, FlexTouch® 1; FT2, FlexTouch® 2; PDC, proportion of days covered.