Table 1.
Reusable insulin pens.
| Study, year | Device studied/device compared | Type of insulin | Participants | Study design | Results |
|---|---|---|---|---|---|
| Berger et al., 1985 (31) | NovoPen® | Short-acting human insulin (Actrapid HM) | 16 adults (10 females, 6 males) aged 21–45 years with T1DM | 6-week randomized, controlled, crossover study. During the first treatment period (3 weeks), the patients were instructed to take short-acting insulin with the new device and during the next 3 weeks to take the insulin with their conventional syringes. Intermediate/long-lasting insulin was taken with usual syringes in both study periods. |
No significant differences (p > 0.05) in blood glucose profile, HbA1c, and hypoglycemia frequency were found between syringes and new device use. 14 patients found that the new device made their life easier. |
| Saurbrey et al., 1985 (51) | NovoPen® | Short-acting insulin (Actrapid HM) | 16 adults (10 females, 6 males) aged 21–45 years with T1DM | 10-month follow-up study of the study by Berger et al. | 15 patients were still using the NovoPen®. There were no differences in mean blood glucose, HbA1c, and number of hypoglycemia (p > 0.05). No significant difference between HbA1c values was found between the outcomes after 6 weeks and 10 months of NovoPen® use. |
| Jefferson et al., 1985 (32) | NovoPen® | Short-acting, human insulin (Actrapid HM) | 11 adolescents (7 boys, 4 girls) aged 12–16 years with T1DM | 3-month observational study. During 4 weeks of the run-in period, the patients were prepared to the study by optimizing the blood glucose levels, and in the end of the fourth week, the therapy was changed from a conventional to multiple-injection regimen (MIR). Next, the patients started a 3-month observation of the MIR treatment with NovoPen® and a single injection of Human Monotard insulin using a conventional syringe. |
10 patients completed the study. There was a non-significant reduction of HbA1c. Moreover, mean blood values were lowered but only in pre-lunch measurements were significantly reduced (p < 0.02). Greater flexibility of timing and size of meals was an overriding advantage of NovoPen® use in the final interview. |
| Walters et al., 1985 (52) | NovoPen® | Short-acting, human insulin (Actrapid HM) | 31 patients (20 males, 11 females) aged 16–57 years with T1DM | 48-week observational study. After 4 weeks of run-in period, the participants started therapy with MIR using NovoPen® with one injection of Human Monotard from the usual syringe. |
27 patients completed the study. Reduction of mean HbA1c values was observed (11.5% in week 0 vs. 10.3% in week 48, p < 0.01). In the final interview, the device was well accepted and 27 patients would like to continue the treatment with NovoPen®. |
| Dahl-Jorgensen et al., 1986 (33) | NovoPen® | Short-acting, human insulin (Actrapid HM) | 10 adults (5 males, 5 females) aged 21–34 years with IDDM. | 6- to 9-month observational study. Patients who had used MIR therapy from conventional syringe for a minimum of 1 year previously started using NovoPen® for short-acting insulin injections (Actrapid HM). A single injection of NPH insulin (Insulatard) was maintained. |
HbA1c increased during the pen injector treatment (from 8.8% to 9.3%; p < 0.01). All but one patient had technical problems with NovoPen®. All participants desired to continue using the pen injector because of the simplicity of the device and greater flexibility of meal time. |
| Jensen et al., 1986 (53) | NovoPen® | Short-acting, human insulin (Actrapid HM) | 20 adults (11 males, 9 females) aged 19–53 years with IDDM. | 24-week observational study. Study started with 8 weeks of run-in period. Next, the patients started multiple injections insulin therapy with NovoPen® and a single injection of intermediate-acting insulin (Protaphane) from the conventional syringe. |
HbA1c improved during the study (from mean 8.7% to mean 7.9%; p < 0.05). The frequency of hypoglycemia was significantly reduced during the training period (from 1.2 attack/patient/week to 0.3 attack/patient/week; p < 0.01). |
| Jorgensen et al., 1988 (38) | Insuject-X (NovoPen® 2) | Intermediate-acting NPH-insulin (Insulatard Human) | 50 adults (28 males, 22 females) aged 18–56 years with IDDM | 6-month randomized, control, crossover trial. All participants were using MIR of soluble insulin (Velosulin Human) from pen injector (Insuject) with a single injection of NPH insulin (Insulatard Human) from the conventional syringe before the study. The first group was continuing multiple injections with the pen injector and NPH insulin from the conventional syringe in the first 3 months of the trial. In the next study period, the group started to administer NPH insulin (Ultratard Human) in the pen injector Insuject-X. The second study group started the trial in the reverse order. |
No differences in the metabolic control were found between both study groups. In the final questionnaires, 86% of the patients found the NPH pen injector less complicated to use than usual syringes. All but 2 patients wished to continue using Insuject-X in the future. |
| Murray et al., 1988 (34) | NovoPen® | Short-acting, human insulin (Actrapid HM) | 78 adults (44 females, 34 males) aged 18–60 years with T1DM | 20-week randomized, controlled trial. After a 6-week run-in period of twice-daily injections with fast and intermediate-acting insulin, patients were randomized into 2 groups. One of them (37 patients) was continuing the two-step insulin regimen with usual syringes. The second group (41 patients) started another regimen with 3 times daily injections of Actrapid made with NovoPen® and a single injection of ultralente insulin (Ultratard). |
No significant differences (p > 0.05) in blood glucose profile, HbA1c, and frequency of hypoglycemia were found between the study groups. Patients presented a high level of satisfaction with NovoPen® for the effect on lifestyle (78%) and increased flexibility (81%). 95% of patients preferred using NovoPen® than conventional syringes. In a questionnaire before the study, 47% of the participants revealed that a rigorous daily schedule for meals and activity was the most important disadvantage. At the end of the study, only 21% and 10% respectively still considered these problems as inconvenient. Moreover, patients expressed greater flexibility of meal times and all but one wanted to continue MIR with NovoPen®. |
| Saurbrey et al., 1988 (54) | NovoPen® | Short-acting, human insulin (Actrapid HM) | 21 adult patients (9 females, 12 males) with T1DM | 20-week randomized, controlled, crossover trial. Comparison of intensified conventional treatment (ICT) with continuous subcutaneous insulin injection (CSII). In the first study period (10 weeks), the patients were treated with MIR using NovoPen® with Actrapid insulin plus a single injection of intermediate-acting insulin (Monotard HM). In the next 10-week period, the participants were treated by CSII with a Medix or Auto-Syringe pump. |
19 patients completed the study. HbA1c declined significantly in both groups with no differences between the responses (ICT 7.6%; CSII 8.7%). Mean blood glucose was slightly lower in CSII (p < 0.05). There were no differences in frequency of hypoglycemia between ICT and CSII. In the questionnaire, all patients found NovoPen® is better than conventional therapy. Moreover, 12 patients would choose ICT with NovoPen® and 6 ones CSII for the future treatment. |
| Houtzagers et al., 1989 (55) | NovoPen® | Short-acting, human insulin (Actrapid HM) | 16 adults (11 males, 5 females) aged 18–63 years with T1DM. | 48-week randomized, controlled, crossover trial. Study started with an 8-week run-in period after which patients were included to 2 study periods lasting 24 weeks each. Participants were allocated randomly in one of the study groups: twice-daily syringe injections with human short-acting (Actrapid HM) and intermediate-acting isophane insulin (NPH; Protaphane HM) or 3 times daily preprandial injections of human short-acting insulin (Actrapid HM) with a single injection of human ultralente insulin (Ultratard HM). |
The mean daily home blood glucose concentration was significantly lower in the pen-injector group (7.1 ± 0.4 vs. 8.2 ± 0.5 mmol I-l, p < 0.05). Neither HbA1c nor fructosamine outcomes did not differ between the syringe and pen injector groups. At the end of the study, 13 patients decided to continue the MIR with NovoPen®. |
| Houtzagers et al., 1989 (56) | NovoPen® | Short-acting, human insulin (Actrapid HM) | 16 adults (11 males, 5 females) aged 18–65 years with T1DM | 12-month randomized, controlled, crossover trial. Following an 8-week run-in period, participants were randomly allocated to twice daily injections of combined human short-acting (Actrapid HM) and intermediate-acting isophane (NPH) insulin (Protaphane HM) with a conventional syringe or administration of human short-acting insulin (Actrapid HM) in 3 preprandial injections from NovoPen® with a single-syringe injection of human ultralente insulin (Ultratard HM). |
HbA1c was not significantly different in both study groups (8.2 ± 0.4 vs. 7.6 ± 0.4%). In the questionnaires completed at the end of the study periods, the patients using the pen injector presented significantly less state anxiety (p < 0.05) and tended to experience a better self-concept as having diabetes (p < 0.06). |
| Tallroth et al., 1989 (57) | NovoPen® | Short-acting insulin (Actrapid HM) | 18 adults (16 males, 2 females) aged 31.0 ± 7.4 years with T1DM | 6-month randomized, controlled, crossover trial. Patients were randomly allocated into group A or B. Group A started a 3-month study period with premeal injections of short-acting insulin with NovoPen® and intermediate-acting insulin with ordinary syringes. In the following 3 months, the therapy was continued with three daily insulin injections of intermediate- and short-acting insulin from conventional syringe. Group B participated in the study in the reverse order. |
Both groups expressed improved mood and well-being in general during multiple insulin injections. Moreover, increased experience of freedom and less content meal times during pen injector treatment were noted. Metabolic control outcomes differ significantly neither in group A nor B after 6 in the end of the study. |
| Tubiana-Rufi et al., 1989 (58) | NovoPen® | Short-acting, human insulin (Actrapid HM) | 15 adolescents (8 boys, 7 girls) aged 5–19.5 years with IDDM | 6- to 24-month observational study. Patients, previously treated with 2 daily injections of mixed insulin, started the therapy with multiple injections of short-acting human insulin (Actrapid HM) using NovoPen® before each meal. A single dose of long-lasting insulin (Ultratard HM) was injected separately with the conventional syringe. |
Significant improvement in metabolic control was observed in the insufficiently controlled group of patients (n = 8) where HbA1c decreased from 8.4 ± 1.8% to 7.3 ± 1.2% (p < 0.05) in the first 6 months of NovoPen® therapy. No more metabolic improvement was observed. The long-term acceptability of multiple injections with NovoPen® was excellent; 100% patients experienced the pen injector as a progress, and 80% would like to continue the treatment in the future. |
| Engstrom, 1990 (39) | NovoPen® | Intermediate-acting insulin NPH (Protaphane HM) | 40 patients with IDDM | 24-week randomized, controlled, crossover trial. Before the study, all participants were treated with multiple injections of short-acting insulin with the pen injector and single injection of basal NPH insulin from the conventional syringe. In the first 12 weeks, one group started using NovoPen® to inject NPH insulin and the second one continued using usual syringes to administer isophane insulin. The second period was followed in the reverse order. |
Outcomes of metabolic control were similar in both study groups. Total soluble insulin doses were significantly higher (31.3 vs. 29.9 U/day, p = 0.02), similarly the ones before breakfast (11.1 vs. 10.6 U/day, p = 0.04) when NovoPen® with NPH insulin were used. All but one patient found it easy to resuspend the isophane insulin in the penfill and was confident in the dose accuracy. 38 (of 40 patients) decided to continue using NovoPen® for basal insulin injections. |
| Henderson et Tindall, 1990 (40) | NovoPen® 2 | Premixed insulin (Actraphane) | 32 patients with IDDM | 3-month observational study. Two groups took part in the trial: volunteers testing NovoPen® II [12 patients (9 males, 3 females)] and the ones continuing twice daily injections with conventional syringe [20 patients (12 males, 8 females)]. The NovoPen® II group completed the quality-of-life (QoL) questionnaire at the beginning of the trial and 3 months later while the control group filled in the one 3 times (to test the reliability of the survey): during the first visit to clinic, 2 weeks later, and at the end of the study. |
67% of patients found the NovoPen® II easy to use, but only half found it more convenient than usual syringes. No significant differences were found in the questionnaire outcomes between the study groups—NovoPen® II did not markedly alter patients’ QoL. |
| Kadiri et al., 1998 (59) | NovoPen® 3 | Intermediate-acting insulin NPH (Insulatard HM) or premixed one (Mixtard HM) | 96 adults with NIDDM | 24-week, open, randomized, crossover trial. Patients with NIDDM and secondary failure (fasting blood glucose > 7.8 mmol/l and HbA1c >25% above the upper limit). All patients were treated with OHAs and diet for at least 1 year before entering the study. The trial consisted of two 12-week periods of insulin administration. Group A started with NovoPen® 3 in Period 1 and crossed over to syringe/vial use in Period 2. Group B followed the study in the inverse order. |
78 patients completed the study. Pain during injections was significantly reduced in the NovoPen® 3 periods (p = 0.0018), including patients in group B who reported lower injection pain using NovoPen® 3 after syringes/vials (p = 0.0003). Acceptance of the injections was significantly higher in the NovoPen® group (p = 0.0059). 89.5% of patients preferred NovoPen® 3 to syringes and vials. |
| Stocks et al., 2001 (43) | HumaPen® Ergo vs. NovoPen® 3 and vial/syringes | Intermediate-acting insulin NPH or premixed 30/70 one | 70 insulin-requiring patients (aged 13–65 years, mean 44.6) with T1DM and T2DM | 5-7 week, multicenter, observational study. Patients administering insulin at least 3 months prior to study entry were asked to answer the questionnaire to assess the level of satisfaction with their current delivery device. Next, participants were instructed how to use HumaPen® Ergo and started injecting insulin in their previous regimen with the new injector. After 5–7 weeks, in the end of the study, patients were asked to answer the questionnaire regarding the acceptability of HumaPen® Ergo, compared with their previous devices. |
>70% of both syringe and NovoPen® 3 users rated HumaPen® Ergo as easy to use in all aspects. The main advantages of the new device were ease of holding during injection, possibility of correcting the doses and the procedure of cartridge changing. At the end of the study, 74% of syringe users and 72% of previous injector users decided to continue administering insulin with HumaPen® Ergo. |
| Ristic et al., 2002 (35) | HumaPen® Ergo | Intermediate-acting insulin NPH or premixed 30/70 one | 230 patients with T1DM (23%) or T2DM (73%) and 24 HCPs | 5- to 7-week multicenter, observational study (consisted of two open-label studies with identical design). Participants who were using another injector before the study started the insulin administration with HumaPen® Ergo. The visits took place in the beginning of the study, after the next 3 weeks, and again in the 7th week of the study. The acceptability of the HumaPen® Ergo was evaluated with a questionnaire in the end of the trial. The HCPs assessed the pen injector with the same criteria as the patients. |
Participants considered HumaPen® Ergo as easy/very easy in learning to use (97%), reading the dose (95%), correcting the dose (97%), and holding during injection (62%). Most of patients (Study 1/2: 89%/93%) found the pen easier/much easier to correct the dose than the previously used injector. 60%/69% of the study group would continue using HumaPen® Ergo and recommend the model to the others HCPs and would recommend the injector because of the ease in dialing back with no insulin waste (80%) and reading the dose (74%). |
| Summers et al., 2004 (21) | Insulin injection pen device (IIPD) vs. vial and syringe | N/A | 242 respondents with T1DM and T2DM (99 insulin users and 143 insulin nonusers) aged 18–83 years (mean 53.4 ± 13.2 years) | US residents completed an email survey with a 19-item self-administered questionnaire. Items were designed to evaluate patients’ experience with IIPD and vial and syringe. The results were analyzed on a 5-point Likert-type scale. Higher scores mean greater agreement. The survey examined ease of use, activity interference, and social acceptability of IIPD and vial and syringe. |
Overall preference for the IIPD was higher than that for vial and syringes among both groups (insulin users and nonusers), mainly because of social acceptability. However, current insulin users claimed that social acceptability and ease of use were the most significant predictors of preference vial and syringes. For insulin non-users, these preference predictors were activity interference and also ease of use. |
| Larbig et al., 2005 (44) | AutoPen® 24 | N/A | 40 adults (20 men, 20 women mean aged 49.3 ± 15.1 years), 20 patients with T1DM and 20 ones with T2DM | 6-month multicenter, open, randomized, crossover study. Before the study, the patients were trained to handle the insulin pens properly. Group A started the study with AutoPen® 24 and after 3 months switched to OptiPen® Pro. Group B followed the study in the reverse order. All the patients participated in all three visits every 12 ± 2 weeks each. After every study period, the patients completed a standardized patient experience and preference questionnaires. |
Both groups presented similar metabolic control and number of hypoglycemic episodes. AutoPen® 24 presented a high level of acceptance in patients (in comparison with OptiPen® Pro) and was preferred by older patients with T2DM. |
| Goksen et al., 2006 (60) | OptiPen® Pro-1 | NPH insulin | 32 patients (mean age 17.0 ± 4.4 years) with T1DM | 6-month observational study. Patients were treated with NPH insulin for at least 6 months before the study. In the beginning of the trial, they were transferred to glargine insulin administered with OptiPen® Pro-1. After 6 months of observations, the patients were asked to complete an inquiry form and rate the OptiPen® Pro-1 on a scale (0 = worst, 5 = best). |
Patients rated the pen as 5 (9% of patients), 4 (38.4%), 3 (26.4%), 2 (11.7%), 1 (8.8%), and 0 (2.9%). Leakage from the injector was noted in 58.8% of subjects, and 38.2% of the ones reported a problem with a dosage button (it was not locking when it was fully depressed after the injection). 61.7% of patients exchanged the pen for an insulin syringe or insulin detemir. |
| Venekamp et al., 2006 (61) | HumaPen® Memoir | Lispro insulin (Humalog®) and human NPH one | 300 participants (aged 18–75 years) with T1DM (38%) or T2DM (62%). | 6- to 10-week multicenter, open-label, single-arm study. The study involved 3 office visits in 6–10 weeks. Patients (who were regularly using pen injectors prior the study) started injections of basal/prandial doses with HumaPen® Memoir. Moreover, patients were recording any complaints that they had during the trial. The complaints were categorized as functional or non-functional. Participants had a possibility to call the investigators if any help with the injector was needed during the study. |
287 patients completed all 3 visits. There were 33 (10.5%) non-functional and 24 (7.6%) functional complaints reported (15 user-related and 8 electronic failures), but none of them resulted in a serious adverse event. No pen-related hypoglycemia and 2 pen-related hyperglycemias were reported. 81.4% of participants preferred the HumaPen® Memoir than their recent injectors. |
| Olsen et al., 2010 (49) | NovoPen® Echo | N/A | 205 participants (79 children aged 7–18 years with T1DM, 78 parents and 48 HCPs). | Observational study. Participants were asked to assess the usability of the device they were using before and the NovoPen® Echo. Firstly, they completed specially designed tasks (setting up the pen, adjusting and injecting a dose, operating the memory function and subjective assessment). Afterward, participants filled up rating scales (1 = most favorable; 6 = least favorable) to rank each pen. |
NovoPen® Echo was highly rated for the design and overall appearance (1.71 ± 0.79) in comparison with NovoPen® Junior (2.02 ± 0.93) and HumaPen® Luxura HD (2.36 ± 1.01). Moreover, 94% parents and 89% children/adolescents found the memory function very easy/easy to use. 80% participants preferred NovoPen® Echo to the other pens (p < 0.0001). |
| Israel-Bultman et al., 2011 (62) | NovoPen® 4 | Human insulin or analogues | 1854 adults with T1DM or T2DM | 12-week, open-label, observational study. The study investigated the preference of NovoPen® 4 usage among patients who previously administered insulin with other pen injectors (NovoPen® 3, HumaPen® Ergo, OptiPen Pro). During the first visit, participants completed the Investigator’s Questionnaire and received a NovoPen® 4 with a complete instruction on how to use it. Moreover, patients’ satisfaction with the previous treatment was analyzed with validated DTSQ. In the final visit (after 12 weeks), the new treatment was evaluated and patients completed the Investigator’s Questionnaire again. |
Patients’ satisfaction improved from 26.5 to 30.5 in DTSQ score (p < 0.0001). 83.3% of patients found NovoPen® 4 easier to use overall (p < 0.0001), and over 70% of them declared that the new device was less complicated to set, read, correct, inject, and change the cartridge than in the previous injectors. 97.2% of healthcare professionals would recommend the NovoPen® 4 to the other patients. |
| Sommavilla et al., 2011 (42) | NovoPen® 4 vs. NovoPen® 3 | N/A | 117 participants: 82 current NovoPen® 3 users (mean age 48.5 ± 1.6 years) and 34 insulin-naïve patients (mean age 61.8 years ± 1.9) with T1DM or T2DM | Multicenter, open-label, crossover study. In the first step of the study, the group of patients currently using NovoPen® 3 were asked to handle NovoPen® 4 and complete a sequence of tasks within 5 min. The second, crossover part of the trial concerned both groups of patients (NovoPen® 3 users and insulin-naïve patients). The first half of every group received a time-recorded training about using NovoPen® 3 before completing a series of tasks. In the end of the tasks, the patients were asked to evaluate handling the device in a questionnaire. In the second step, the participants completed the same sequence of tasks with another device—NovoPen® 4. The other half of the study groups assessed the injectors in the reverse order. |
Current NovoPen® 3 users completed the tasks with NovoPen® 4 in an average time of 1.94 min (range, 0.57–4.98 min). Survey responses presented less difficulty and more confidence in handling NovoPen® 4 than NovoPen® 3 in both groups. 96.3% NovoPen® 3 users and 100% insulin-naïve patients preferred to use NovoPen® 4 (p < 0.0001). |
| Klonoff et al., 2013 (50) | JuniorSTAR® | N/A | 167 participants (nurses working with children with T1DM, children/adolescents with T1DM and their parents) | Observational study. In the study, the following participated: 109 nurses working with children with T1DM; 16 parents of children aged < 5 years; 8 children aged 6–12 years; 12 parents of children aged 6–12 years and 22 adolescents aged 13–18 years. Participants were asked to assess the JuniorSTAR® pen injector on 3 five-point scales: - when rating the product: 1 = very poor; 5 = very good or 1 = very difficult; 5 = very easy, - when asked to agree/disagree: 1 = completely disagree; 5 = completely agree. Positive response means a percentage of either a 4 or a 5 score. |
98% of the study population found that the insulin injector helped patients achieve a high level of dose dialing accuracy (93% of children/parents and 100% of nurses). The key advantages of the JuniorSTAR® (found in at least 84% of all participants) are practicality, ease of carrying (84%), ease of reading the dose (96%), ease of dialing back (87%), and a suitable injection force (87%). When the respondents were asked to describe the pen in one word, the most common replies were as follows: practical, easy, and simple. |
| Grabner et al., 2013 (18) | Pen vs. vial | Glargine insulin | 2,531 insulin-naive patients with T2DM (1384 pen and 1147 vial users) | Retrospective, observational cohort study. Patients were included into the study using data from HealthCore Integrated Research Database. Patients were treated with at least 1 oral antidiabetic or glucagon-like peptide-1 receptor agonist (GLP-1) at baseline. The observations were provided 6 months before first insulin use (first insulin prescription) and 12 months later (follow-up period). The analysis covered 1-year outcomes including treatment persistence and adherence, HbA1c, hypoglycemia rates and healthcare costs. |
Patients initiating insulin therapy with pens (glargine) were more persistent (60.6% vs. 50.1%, p < 0.001), adherent (medication possession ratio, 0.73 vs. 0.57, p < 0.001) and with lower HbA1c levels in follow-up (mean adjusted change, -1.05 vs. 0.73, p < 0.001) in comparison to vial patients. In both cohorts, hypoglycemia occurred at similar rates (3.8% vs. 5.2% respectively, p = 0.21). Study drug costs were higher among pen users ($1164 vs. $762, p < 0.001). |
| Asche et al., 2013 (15) | Pen vs. vial | Aspart insulin | 11,588 adults patients from the MarketScan database (6,065 pen users and 5,523 vial ones) and 8,294 adults from the LifeLink database (4,512 pen users and 3,782 vial ones) with T2DM and T1DM | Longitudinal retrospective analysis based on the MarketScan and IMS LifeLink databases. Study groups contained patients initiating treatment with insulin aspart administered by pen or vial and syringe. The data were collected based on outpatient pharmacy claims data. During the 12-month post-index period, patients had at least 2 claims for the index treatment. |
Vial and syringe use was characterized by 35% greater odds of at least one hypoglycemic episode than pen use (p < 0.001) in the MarketScan database and 44% greater odds in the LifeLink database (p < 0.001). Use of vial and syringes was associated with 89% and 62.7% (respectively, both p < 0.001)) greater healthcare costs because of hypoglycemic events than use of pens. |
| Ahmann et al., 2014 (20) | Pen vs. vial | Glargine insulin | 405 insulin-naïve adults with T2DM (aged 18–85 years) | Randomized, open-label, crossover study. Patients received basal insulin (glargine) in one of two treatment sequences (2 weeks of using pen followed by 2 weeks of using vial and syringe or vice versa). Patient device preference was evaluated by the Insulin Injection Preference Questionnaire in the first end point (at week 4—the end of the crossover period). Then, patient preference and HCP recommendation were assessed with one global item and 3 others (blood glucose control, reluctance to use insulin, long-term insulin use) using a 5-point scale (1 = not preferred, 5 = preferred/recommended). Next, patients were re-randomized to pen or vial and syringe group for further observation (6, 10, and 30 weeks) to evaluate clinical end-points (HbA1c, fasting blood glucose levels) and safety outcomes (hypoglycemia, adverse events). |
Pens were preferred by patients and strongly recommended by HCPs over vials and syringes (p < 0.001). Corresponding responses were observed by both groups (patients and HCPS) in the three subscale items. Fasting glucose levels, HbA1c levels, and hypoglycemia rates were comparable in both pen and vial/syringe users. |
| Lasalvia et al, 2016 (23) | Pen vs. vial | Glargine, detemir, NPH, aspart, premixed human 30/70, lispro | Study groups generally composed of adults with T2DM. | Meta-analysis. 10,348 articles from 8 different databases, of which 17 studies were selected: 7 experimental and 10 analytical. Studies concerned a comparison of insulin administration by pen devices with vial and syringes. HbA1c, hypoglycemia, adherence, persistence, patient preference, and QoL were analyzed. |
Pen devices presented better results in mean HbA1c change, frequency of hypoglycemia, adherence, and persistence in comparison with vial and syringes. Among patients with good metabolic control (HbA1c < 7%) no difference was observed. Tendency to prefer pen devices was observed, however unvalidated tools were used in the analysis. |
| Gorska-Ciebiada et al., 2020 (36) | GensuPen® | Short- and long-acting insulins, premixed human 30/70, 40/60 and 50/50 ones | 4,513 adults (mean age 65.3 ± 10.2 years) with T2DM | 12-week, multicenter, observational trial EGIDA II (Education and GensuPen® In Diabetology II) Participants were divided into 2 groups: A—treated with GensuPen®; B—treated with other pens. Before the study, all the subjects were educated by trained HCPs. Patients were asked to complete the questionnaires regarding injection parameters, pain scale, and satisfaction of the treatment before (visit 1) and after the study (visit 2). |
Patients’ utility, comfort, and satisfaction with the treatment increased, wherein group A presented a greater increase. In both study groups, mean glucose levels (from self-control diaries) were significantly lower after 3 months of the trial, but group A presented a greater difference between visits 1 and 2. In both groups, a significant decrease in sensation of pain was observed, with a greater decrease in group A. Moreover, education of the patients could help to improve the metabolic control and technique of insulin injections, reduce BMI and pain sensation. |
| Masierek M et al., 2020 (27) | GensuPen® | Gensulin® R, Gensulin® N, and premixed insulins M30, M40, and M50 | 10,309 adults (mean 63.3 ± 12.0 years) with T2DM | 4-week multicenter, prospective, observational, open-label study. The trial consisted of one visit in the office (during study enrolment) and two telephone contacts (performed 7 days after enrolment and 4 weeks ± 7 days later). All patients were educated about the proper use of GensuPen® and maintained on Gensulin® (Gensulin® R, N or premixed M30, M40, M50). Moreover, participants had an opportunity to contact dedicated helpline in case of any technical problems with the injector. During the first telephone contact, patients were asked about any problems and needed information regarding GensuPen® use. The next call (after the study) was aimed at assessing patients’ safety and comfort concerning GensuPen®. The interview was based on two questionnaires concerning evaluation of the GensuPen® and comparing the new injector with previously used ones (if applicable). |
GensuPen® was rated as very good in confirmation of successful administration (92.0%), setting a dose (87.8%), trigger location (80.9%), and injection force (75.0%). Adverse events occurred in 0.6% of participants and none was serious. Moreover, the overall safety of the device was rated as high (severe hypoglycemia affected only 0.2% of the study group). |
| Boye et al., 2021 (25) | N/A | 504 adults (251 UK, 253 US) treated with injections of insulin (49.6%) or GLP-1 receptor agonist (50.4%) | Observational, online survey study. Patients treated with insulin or GLP-1 receptor agonist were presented with a list of 17 characteristics of injectable medication and ask to indicate which were most important for them. |
The most frequently selected characteristics were confidence in administering the correct dose (n = 300, 59.5%); ease of selecting the correct dose (n = 268, 53.2%); overall ease of using the injection device (n = 239, 47.4%); frequency of injections (n = 223, 44.2%); ease of carrying the device when necessary to inject away from home (n = 190, 37.7%). Respondents least often chose dose escalation (n = 79, 15.7%); handling the needle (n = 74, 14.7%); connectivity to an electronic device (n = 70, 13.9%); and the time required to prepare and inject each dose (n = 62, 12.3%). |
DM, diabetes mellitus; T2DM, type 2 diabetes mellitus; GLP-1, glucagon-like peptide 1; IIPD, insulin injection pen device; DTSQ, Diabetes Treatment Satisfaction Questionnaire. N/A, not applicable.