Titration of Long-Acting Insulin Using Continuous Glucose Monitoring and Smart Insulin Pens in Type 1 Diabetes: A Model-Based Carbohydrate-Free Approach

ObjectiveMultiple daily injections (MDI) therapy is the most common treatment for type 1 diabetes (T1D), consisting of long-acting insulin to cover fasting conditions and rapid-acting insulin to cover meals. Titration of long-acting insulin is needed to achieve satisfactory glycemia but is challenging due to inter-and intra-individual metabolic variability. In this work, a novel titration algorithm for long-acting insulin leveraging continuous glucose monitoring (CGM) and smart insulin pens (SIP) data is proposed.MethodsThe algorithm is based on a glucoregulatory model that describes insulin and meal effects on blood glucose fluctuations. The model is individualized on patient’s data and used to extract the theoretical glucose curve in fasting conditions; the individualization step does not require any carbohydrate records. A cost function is employed to search for the optimal long-acting insulin dose to achieve the desired glycemic target in the fasting state. The algorithm was tested in two virtual studies performed within a validated T1D simulation platform, deploying different levels of metabolic variability (nominal and variance). The performance of the method was compared to that achieved with two published titration algorithms based on self-measured blood glucose (SMBG) records. The sensitivity of the algorithm to carbohydrate records was also analyzed.ResultsThe proposed method outperformed SMBG-based methods in terms of reduction of exposure to hypoglycemia, especially during the night period (0 am–6 am). In the variance scenario, during the night, an improvement in the time in the target glycemic range (70–180 mg/dL) from 69.0% to 86.4% and a decrease in the time in hypoglycemia (<70 mg/dL) from 10.7% to 2.6% was observed. Robustness analysis showed that the method performance is non-sensitive to carbohydrate records.ConclusionThe use of CGM and SIP in people with T1D using MDI therapy has the potential to inform smart insulin titration algorithms that improve glycemic control. Clinical studies in real-world settings are warranted to further test the proposed titration algorithm.SignificanceThis algorithm is a step towards a decision support system that improves glycemic control and potentially the quality of life, in a population of individuals with T1D who cannot benefit from the artificial pancreas system.

Automated Bolus Calculators and Connected Insulin Pens: A Smart Combination for Multiple Daily Injection Insulin Therapy

Although automated bolus calculators (ABCs) have become a mainstay in insulin pump therapy, they have not achieved similar levels of adoption by persons with diabetes (PWD) using multiple daily injections of insulin (MDI). Only a small number of blood glucose meters (BGMs) have incorporated ABC functionality and the proliferation of unregulated ABC smartphone apps raised safety concerns and eventually led to Food and Drug Administration (FDA)–mandated regulatory oversight for these types of apps. With the recent introduction of smartphone-connected insulin pens, manufacturer-supported companion ABC apps may offer an ideal solution for PWD and health care professionals that reduces errors of mental math when calculating bolus insulin dosing, increases the quality of diabetes data reporting, and improves glycemic outcomes.

Development of an Insulin Pen is a Patient-Centric Multidisciplinary Undertaking: A Commentary

The goal of human-centered insulin pen design is to relieve the treatment burden of a chronic condition and help affected individuals to feel free of disease. The patient as well as their entire ecosystem should be considered. At Novo Nordisk A/S, we believe that embedding human-centered design at the heart of our development processes is best achieved with multidisciplinary experts in-house to work alongside product development teams and, importantly, the end user. Novo Nordisk introduced the first commercially available insulin pen in 1985 and has continued to develop reusable/durable and prefilled insulin pens to meet different patient needs, through to the latest NovoPen 6 and NovoPen Echo Plus with SMART technology. Human-centered design is essential for delivering meaningful and practical solutions for individuals with diabetes.

A review of reusable insulin pens and features of TouStar—a new reusable pen with a dedicated cartridge

Background Since the introduction of the first reusable insulin pen, the advancement in the design of these pens is still ongoing to develop a safe, more efficacious, less painful, and easy to use insulin pen device. Main body Possible errors in insulin delivery can occur at any stage of insulin delivery such as during the prescription stage, dispensing stage, or at administration stage. Mismatch of the insulin pen and cartridge is not uncommon and is a potential risk for individuals with diabetes due to serious consequences associated with incorrect insulin usage. The similarities in insulin cartridges of different manufacturers with regard to color and product names could lead to mix-up of insulin pens and cartridges. These unmet needs have led to the ongoing search for developing insulin pens that can address these errors and provide more efficacious and safer choices for patients with diabetes. Conclusion This review provides an overview of currently available reusable pens in the market and highlights the features of TouStar®, a new reusable pen with a dedicated cartridge intended to mitigate the risk of mismatch of the cartridge.

The Role of Human-Centered Design in Insulin Pen Innovation and the Future of Insulin Delivery

Insulin pens have made a dramatic impact on diabetes care, with evidence suggesting that they promote performance of self-care and reduce negative health outcomes for people with diabetes. Human-centered design (HCD), practiced by IDEO for over 40 years and together with Eli Lilly for over 15 years, has helped to design insulin pens that evolved with the needs of people with diabetes. HCD employs unique methods that help to uncover people’s needs and design with them in mind. The future of diabetes care is bright with the ongoing application of HCD methodology in this space.

Human Insulin (Entuzity KwikPen)

CADTH recommends that Entuzity KwikPen should be reimbursed by public drug plans to improve glycemic control in adults and children with diabetes mellitus, if certain conditions are met. Entuzity KwikPen should only be reimbursed if it is initiated by a specialist with experience in treating severe insulin resistance and if the cost of Entuzity KwikPen does not exceed the least expensive basal or bolus combination insulin pens or cartridges. Entuzity KwikPen should only be covered to treat patients with diabetes mellitus with unacceptable glycemic control who require more than 200 units of insulin per day, with or without other therapies.

Inspecting Insulin Products Using Water Proton NMR. I. Noninvasive vs Invasive Inspection

Background: There is a clear need to transition from batch-level to vial/syringe/pen-level quality control of biologic drugs, such as insulin. This could be achieved only by noninvasive and quantitative inspection technologies that maintain the integrity of the drug product. Methods: Four insulin products for patient self-injection presented as prefilled pens have been noninvasively and quantitatively inspected using the water proton NMR technology. The inspection output is the water proton relaxation rate R2(1H2O), a continuous numerical variable rather than binary pass/fail. Results: Ten pens of each product were inspected. R2(1H2O) displays insignificant variation among the 10 pens of each product, suggesting good insulin content uniformity in the inspected pens. It is also shown that transferring the insulin solution out of and then back into the insulin pen caused significant change in R2(1H2O), presumably due to exposure to O2 in air. Conclusions: Water proton NMR can noninvasively and quantitatively inspect insulin pens. wNMR can confirm product content uniformity, but not absolute content. Its sensitivity to sample transferring provides a way to detect drug product tampering. This opens the possibility of inspecting every pen/vial/syringe by manufacturers and end-users.