Debra A. Ignaut

Comparative Device Assessments Humalog KwikPen Compared With Vial and Syringe and FlexPen

Purpose The purpose of this study was to compare pen device-naïve patients’ preferences for Humalog® KwikPen™ (insulin lispro injection) (Eli Lilly and Company, Indianapolis, IN) to use of a vial and syringe and FlexPen® (insulin aspart injection) (Novo Nordisk A/S, Bagsvaerd, Denmark). Methods This open-label, randomized, crossover 1-day study tested the hypotheses that KwikPen was preferred to vial and syringe, and if this was found to be a significant preference, that KwikPen was preferred to FlexPen. Accuracy of doses prepared, ease of use via insulin device assessment battery, and preference via insulin device preference battery were administered following each pen evaluation, and a final preference question administered following the evaluation of both pens. Clinical measures were not included as subjects injected into an appliance to simulate the injection experience. Primary outcome variables were evaluated by Question 13 of the insulin device preference battery and the final preference question. Results Among 232 enrolled patients randomized to 1 of 4 sequences (n = 58), Humalog KwikPen was significantly preferred over vial and syringe and over FlexPen. After patients were asked to assess Humalog KwikPen or FlexPen versus V&S by choosing “strongly agreed” or “agreed” to the following attributes: easy to use, easy to hold in their hands when injecting, and easy to press the injection button, the results exhibited significant differences in patient responses. Humalog KwikPen was significantly more accurate and was preferred to vial and syringe in appearance, quality, discretion, convenience, public use, easy to learn, easy to use, reliability, dose confidence, following insulin regimen, overall satisfaction, and recommendation to others. Conclusions Humalog KwikPen was significantly preferred over vial and syringe and FlexPen. When compared with vial and syringe, Humalog KwikPen and FlexPen were easier to use and operate, demonstrated superior accuracy of doses prepared, and preferred by pen-naïve users.

Safe and Effective Use of the Once Weekly Dulaglutide Single-Dose Pen in Injection-Naïve Patients With Type 2 Diabetes

Background: This 4-week, phase 3b, multicenter, open-label, single-arm, outpatient study demonstrated the safe and effective use of the dulaglutide single-dose pen containing 0.5 mL of placebo for subcutaneous injection in injection-naïve adult patients with type 2 diabetes (T2D), with A1C ≤ 8.5% (69 mmol/mol), BMI ≥ 23 kg/m2 and ≤ 45 kg/m2. Method: Patients completed a modified self-injecting subscale of the Diabetes Fear of Injecting and Self-Testing Questionnaire (mD-FISQ) and were trained to self-inject with the single-dose pen. Patients completed the initial self-injection at the site, injected at home for 2 subsequent weeks, and returned to the site for the final injection. The initial and final self-injections were evaluated for success; the final (initial) self-injection success rate was the primary (secondary) outcome measure, and the primary (secondary) objective was to demonstrate this success rate as being significantly greater than 80%. Patients recorded their level of pain after each injection. After the final injection, patients completed the mD-FISQ and the Medication Delivery Device Assessment Battery (MDDAB) to assess their perceptions of the single-dose pen, including ease of use and experience with the device. Results: Among 211 patients (mean age: 61 years), the primary objective was met, with a final injection success rate of 99.1% (95% CI: 96.6% to 99.7%). Among 214 patients, the initial injection success rate was 97.2% (95% CI: 94.0% to 98.7%), meeting the key secondary objective. Overall, most patients (>96%) found the device easy to use, were satisfied with the device, and would be willing to continue to use the single-dose pen after the study. There was a significant reduction (P < .001) from baseline to study end in patients’ fear of self-injecting, as measured by the mD-FISQ. Conclusions: The dulaglutide single-dose pen was found to be a safe and effective device for use by patients with T2D who were injection-naïve. A positive injection experience is an important factor for patients and providers when initiating injectable therapy.

FlexPen® and KwikPen™ Prefilled Insulin Devices: A Laboratory Evaluation of Ergonomic and Injection Force Characteristics

Background: Advances in insulin pen technology continue to improve the usability of these devices for patients with diabetes. In this study, ergonomic features and injection force, as measured by glide force (GF) and glide force variability (GFV), were evaluated for the new Humalog® Mix75/25 KwikPen™ (KwikPen) and compared with the NovoLog® Mix 70/30 FlexPen® (FlexPen). Methods: Fifty prefilled insulin pen devices (25 of each type) were measured for diameter at the cartridge holder and dose window, length and weight with cap attached, and thumb reach at 30 and 60 units. GF was also determined for 100 devices (50 of each type); GFV at 30 and 60 unit doses was calculated for the plateau portion of the force curve based on the minimum and maximum force measured in that portion of the curve. Results: While FlexPen was lighter in weight than KwikPen, and presented a slightly smaller diameter at the cartridge holder and dose window, KwikPen had a shorter overall pen length compared to FlexPen, with a shorter thumb reach at both the 30- and 60-unit dose settings. The maximum GF for KwikPen was less than FlexPen at both the 30-unit (3.42 vs 5.36 lb, p <0.0001) and 60-unit doses (3.61 vs 5.62, p <0.0001). KwikPen GFV was lower across both doses (mean difference: −0.46 lb at 30 units, −0.44 lb at 60 units; p <0.0001 for both). Conclusions: While FlexPen was lighter with a slightly smaller cartridge holder and dose window diameter, KwikPen was shorter in length with less thumb reach than FlexPen. KwikPen also demonstrated lower GF and GFV, resulting in a smoother injection profile than FlexPen. These features of KwikPens design and function may offer important advantages for the user during insulin administration.

Engineering study comparing injection force and dose accuracy between two prefilled insulin injection pens

Abstract Objective: This study compared injection force (measured by glide force [GF] and glide force variability [GFV]) and dosing accuracy of the Humalog KwikPen* (prefilled insulin lispro [Humalog† pen, Eli Lilly and Company, Indianapolis, IN) and the Next Generation FlexPen‡ (prefilled insulin aspart [NovoRapid§ pen, Novo Nordisk A/S, Bagsværd, Denmark). * Humalog KwikPen is a registered trademark of Eli Lilly and Company, Indianapolis, IN, USA. † Humalog is a registered trademark of Eli Lilly and Company, Indianapolis, IN, USA. ‡ FlexPen is a registered trademark of Novo Nordisk A/S, Bagsværd, Denmark. § NovoRapid is a registered trademark of Novo Nordisk A/S, Bagsværd, Denmark. Research design and methods: A total of 100 prefilled insulin pens (50 insulin lispro pens, 50 insulin aspart pens) were tested using two dose sizes (30 U and 60 U). In all, 50 devices (25 of each type) were tested at 10 U/s dosing speed and 50 were tested at 6.6 U/s. Devices were used per manufacturer instructions. Dose accuracy (represented as absolute dose error %), maximum and average GF, and GFV data were automatically collected by the test system for all datasets (dose size/dosing speed/device type). The test system controlled for potential dosing errors. Results: The insulin lispro pen demonstrated a significantly lower median maximum GF at both dosing speeds: (2.83 vs. 3.92 lbs [30 U] and 3.00 vs. 4.14 lbs [60 U]) at 10 U/s; (1.85 vs. 2.93 lbs [30 U] and 2.14 vs. 3.02 lbs [60 U]) at 6.6 U/s, all p < 0.0001. For all datasets, the median GFV was significantly lower for the insulin lispro pen, p < 0.0001. Median dose error was comparable between device types when tested at 10 U/s dosing speed; however, at 6.6 U/s, the median dose error was significantly lower for insulin lispro pen compared to insulin aspart pen (0.47 vs. 0.67% [30 U] and 0.50 vs. 0.78% [60 U], both p < 0.05). Conclusions: The insulin lispro pen had significantly lower median GF and GFV compared with insulin aspart pen when tested at two dose sizes and two dosing speeds. Median dose error was similar between the device types at the 10 U/s dosing speed, but median dose error was significantly lower for the insulin lispro pen at the 6.6 U/s dosing speed. A limitation of this study was that it was executed as an open label study.

Comparison of Insulin Diluent Leakage Postinjection Using Two Different Needle Lengths and Injection Volumes in Obese Patients with Type 1 or Type 2 Diabetes Mellitus

Background: Smaller gauge, shorter needles have been shown to be as safe and effective for insulin delivery as longer needles in many patients. However, in obese patients with diabetes, results have been inconsistent with regard to the impact of needle length on leakage of injectate. Methods: A single-blind, randomized, two-period, crossover study compared injections with 5 mm needles to 8 mm needles regarding leakage, pain, bleeding, and bruising at abdominal injection sites in obese patients with diabetes using 20- and 60-unit (U) volume equivalent injections of sterile insulin diluent. Results: Fifty-six patients (54% male; mean age 56 years; mean body mass index of 36 kg/m2) with type 1 (n = 13) or type 2 (n = 43) diabetes participated. Median leakage (U) was similar for both needles [0.04 (5 mm/20 U) vs 0.02 (8 mm/20 U), P = .32; and 0.04 (5 mm/60 U) vs 0.02 (8 mm/60 U), P = 48]. Pain scores (mean) were similar [1.27 (5 mm/20 U) vs 1.14 (8 mm/20 U), P = .75, and 1.68 (5 mm/60 U) vs 0.95 (8 mm/60 U, P = .21)]. The proportion of injections with bleeding [10.8% (5 mm/20 U) vs 5.83% (8 mm/20 U), P = .23, and 4.92% (5 mm/60 U) vs 6.56% (8 mm/60 U), P = .73] and the proportion of patients with bruising [8.11% (5 mm/20 U) vs 10.81% (8 mm/20 U), p = .56, and 21.05% (5 mm/60 U) vs 26.32% (8 mm/60 U), p = .65] at injection sites were similar. Mean bruise size (mm) [0.73 (5 mm/20 U] vs 2.68 (8 mm/20 U), P = .23; and 1.11 (5 mm/60 U) vs 4.21 (8 mm/60 U), P = .08] at injection sites was similar. Conclusions: This study supports the suitability of the 5 mm needle for the injection of insulin in obese patients with diabetes.

HumaPen® Memoir™: a novel insulin-injecting pen with a dose-memory feature

Optimizing glycemic control may help to reduce the risks of diabetes complications, but it is often difficult to achieve, partly owing to poor treatment adherence. One barrier to adherence is forgetfulness. The HumaPen® Memoir™ pen is the only electronic reusable insulin pen with a multiple-dose memory feature. This enables the device to store information regarding dates and times of the previous 16 doses of insulin, including priming doses. The pen has a digital display and a two-way dial to minimize waste of insulin. The digital display facilitates accurate dose selection. Both patients and healthcare providers rate as important the pen’s ability to confirm administered doses and times, its overall ease of injection and display readability, and its minimal waste when adjusting dose settings.

A Comparison of Glide Force Characteristics Between 2 Prefilled Insulin Lispro Pens

Background: Glide force, average glide force, and glide force variability of the insulin lispro 200 units/mL pen (Eli Lilly and Company, Indianapolis, IN, USA) were compared to the Humalog® KwikPen® 100 units/mL pen (hereafter, KwikPen; Eli Lilly and Company, Indianapolis, IN, USA). Methods: Data were collected on 2 doses, 2 injection speeds, and 2 needle types. Results: Insulin lispro 200 units/mL pen showed significantly lower maximum glide force, average glide force, and glide force variability than the KwikPen across all combinations of dose size, dose speed, and needle type. Conclusions: The lower glide force observed with the insulin lispro 200 units/mL pen offers another treatment option for patients with type 1 or type 2 diabetes who require greater than 20 units of mealtime insulin daily.

Subcutaneous Injection Depth Does Not Affect the Pharmacokinetics or Glucodynamics of Insulin Lispro in Normal Weight or Healthy Obese Subjects

Background: An 8-mm needle length is commonly used for insulin injections; however, recent recommendations suggest shorter needles may help patients avoid intramuscular injections and reduce pain, while maintaining adequate glucose control. The goal of these analyses was to compare the pharmacokinetics (PK) and glucodynamics (GD) of insulin lispro after a 5-mm or an 8-mm injection depth administration in 2 populations: normal weight (study 1) or obese (study 2). Methods: In both open-label, randomized, 2-period crossover euglycemic clamp studies, subjects received single 0.25 U/kg insulin lispro doses on 2 occasions (at 5-mm and 8-mm injection depths); samples for PK and GD analyses were collected up to 6 hours postdose. Noncompartmental PK parameters AUC0-tlast, AUC0-∞, Cmax and GD parameters Gtot, Rmax, tRmax were log-transformed prior to analysis using a mixed effects model. Results: There were no apparent differences between PK profiles at the 5-mm or 8-mm injection depth in either study, demonstrated by the ratios of geometric means of AUC0-tlast, AUC0-∞, and Cmax being close to 1, with 90% confidence intervals (CI) within (0.80, 1.25). There were no apparent differences between GD profiles at either injection depth with the ratios of Gtot and Rmax near unity and 90% CIs that included 1. In both studies, the tRmax values were similar between injection depths, with a small median of pairwise differences and a 90% CI that included zero. Conclusions: Injection depths in the 5-8 mm range did not affect the PK or GD of insulin lispro in normal weight or obese subjects.

Lessons Learned during the Development of HumaPen® Memoir™, an Insulin Pen with a Memory Feature

Insulin pens are developed to address specific needs of diabetes patients for their pens, such as ease of use, portability, and discreetness. Like many consumer-based products, the development of insulin pens can pose significant challenges to the development team in that they must balance substantial accuracy requirements with aesthetic desires. The HumaPen® Memoir™ team learned valuable lessons throughout the development process that may be worth highlighting. A keen understanding of the unmet needs of the patient population and a skillfully planned product generation map are critical to successful device development. A development team must decide whether to use a Quality Functional Deployment or system engineering-based development plan and, additionally, recognize where proof of concept ends and product development begins to maintain a strict timeline for the project. A proficiency in understanding and managing technical risk is critical to ensure a timely and high-quality product launch to the marketplace.

Analysis and Perspective of Dosing Accuracy and Insulin Flow Rate Characteristics of a New Disposable Insulin Pen, FlexTouch, Compared with SoloSTAR:

Pen injectors for the administration of insulin have been available since the 1980s. The first insulin pen, NovoPen®, was introduced by Novo in 1985 (http://www.novonordisk.com/about_us/history/step-by-step.asp). In the years since, insulin pens have seen innovation in both features and functionality, and many more manufacturers have entered the market. This analysis discusses several features and design alternatives of insulin pens and comments on a new study by Bohnet and coauthors in this issue of Journal of Diabetes Science and Technology that compared the dosing accuracy of the spring-driven FlexTouch® (FT; Novo Nordisk; insulin aspart) with that of the manually operated SoloSTAR® (Sanofi; insulin glulisine). The volumetric flow rate of insulin delivery with FT was also evaluated.