A recent publication by Aanstoot et al. raised important issues for consideration regarding precision dosing of insulin with injection therapy (1). Defined as delivering the correct dose, authors note precision dosing is a lesser-studied factor that contributes toward better glycemic management. Here the discussion is broadened to discuss additional factors critical to the larger topic of precision insulin management, of particular importance to the pediatric type 1 diabetes (T1D) population.
An international comparison study in people with T1D reported a median A1c range of 7.4%-9.4% across countries and age groups, exceeding target A1c recommendations (2). Adolescents and young adults are particularly challenged in reaching glycemic targets as highlighted in the T1D Exchange Registry data showing ~81% of individuals aged 13- 25 years failed to meet A1c targets (3, 4). This data underscores the need for timely insulin regimen intensification. Individualized insulin therapy settings that are fine-tuned on an ongoing basis are critical for smart insulin delivery systems whether pump or pen to be effective and are important factors in precision insulin management
A data-driven approach to insulin therapy will be critical to any discussion of precision insulin management. The three hallmarks of a data-driven practice model for intensive insulin therapy include (5):
- Identify: Help individuals make an informed decision regarding the best method of insulin delivery for their circumstances and preferences
- Configure:Individualize insulin therapy settings, schedule, dose and glucose check reminders; sync to available glucose monitors to integrate related data
- Collaborate: On a timely, ongoing basis use the data in partnership with the person with diabetes to intensify the insulin regimen and fine-tune the insulin therapy settings.
The majority of insulin dependent individuals are on injection therapy today across the globe, many perhaps by default versus choice (6). Most are using traditional insulin pens or vial and syringe with no intelligent dosing support. On the opposite end of the spectrum are smart insulin pump systems. While these increasingly advanced systems are tremendous tools, they are perceived by many to be costly, inconvenient and complex, requiring considerable commitment and serving as a constant reminder of diabetes. Less than 30% of individuals with T1D and less than 1% with type 2 diabetes (T2D) use insulin pumps (7). Other options include basic patch pumps and inhaled insulins which address some of the barriers to pump therapy but currently offer no intelligent dosing support. Smart Insulin Pens allow individuals on injection therapy to finally have the precise dosing support they need with a low-cost, familiar durable insulin pen paired to a smart diabetes management app.
The American Diabetes Association Standards of Medical Care in Diabetes 2020 opened the Technology in Diabetes chapter noting, “there is no one-size-fits-all approach to technology in diabetes care” (8). Recommendations regarding insulin delivery are listed below.
7.17 Base decision on: Patient preference, insulin type, dosing regimen, cost and self-management capabilities. B
7.18 Insulin pens or injection aids may be considered for patients with dexterity issues or vision impairment to facilitate accurate insulin dosing. C
7.19 Patients using insulin should have an examination of insulin injection/infusion sites on a routine basis – at least annually and if there are clinical issues related to insulin delivery. E
7.20 Smart pens may be useful for some patients to help with dose capture and dosing recommendations. E
7.21 FDA approved insulin dose calculators/decision support systems may be helpful for titrating insulin doses. E
7.22 Competent patients using diabetes devices should be allowed to use them in an inpatient setting when proper supervision is available. E
The standards further note, in reference to smart insulin delivery devices, “provider input and education can be helpful for setting the initial dosing calculations with ongoing follow-up for adjustments as needed” (8). Inputting the correct, individualized settings in the smart insulin pen is critical for precise insulin management. It is also important to assess and optimize basal insulin prior to fine-tuning the insulin therapy settings. A guide to determining and fine-tuning insulin therapy settings and basal insulin is available for download at Companion Medical’s website. An Insulin Institute Insights webinar was devoted to this topic and is available to watch OnDemand.
It will be necessary to refine these insulin therapy settings over time as life and diabetes evolve; pediatric patients grow, activity, schedules and living situations change and weight is gained (or lost). Integrated data reports from smart insulin pens enable use of data to optimize the insulin regimen and fine-tune therapy settings. These data reports are available remotely enabling remote patient monitoring and virtual care facilitating more timely therapy adjustments.
Smart Insulin Pens Outperform Syringes
Insulin pens have consistently outperformed syringes as delivery devices due to their greater accuracy and precision of dosing, ease-of-use, and patient preference. These advantages make them better suited to administer insulin in hypoglycemia-prone insulin-sensitive people with T1D, particularly younger children (1). ISO 11608-1 is the international performance standard for pen injectors. In order to pass, devices must be accurate after being subjected to temperature and humidity extremes, vibration, free fall drop, and dust and moisture exposure. This is a statistical requirement, meaning there is a bell curve centered on 0.5U. A manufacturer must show with high confidence that doses are tightly clustered around the nominal value of 0.5U. Companion Medical’s InPen meets the requirements of ISO 11608-1 which is the basis of FDA clearance.
Aanstoot et al, emphasize the importance of 0.5 Unit dosing capability particularly for people who need very small dosages (1). Individuals must round their dose to the nearest whole unit, if using a standard insulin pen, thereby administering more or less insulin than required. Half-unit insulin pens, by offering finer insulin dosing, help address this issue. Advantages of half unit dosing include accurate and precise delivery of low-dose insulin, improved glycemia while preventing hypoglycemia and enhanced adherence. This may contribute to better management of diabetes by allowing flexible dosing for erratic eating situations, varying physical activities or illnesses by offering the ability to deliver corrective doses in small increments. Those utilizing carbohydrate counting to determine insulin dosing may benefit from half-unit insulin delivery to better match their insulin-to-carbohydrate ratio. Currently, five half-unit insulin pens are commercially available in the United States: HumaPen Luxura HD, NovoPen Echo, Junior-STAR, Humalog Junior Kwikpen, and InPen. All pens except the JuniorSTAR have demonstrated accuracy at 0.5U of insulin (1).
Priming before each insulin dose is an important part of precision dosing. Priming removes the air from the needle and cartridge that may collect during normal use ensuring the full dose is delivered. It is important that pen users prime before every injection. A stage 4 smart insulin pen, as defined by Kerr et al, must be able to differentiate prime from therapeutic doses (6). This is necessary in order to accurately track active insulin or insulin on board. In order to safely correct between meal time doses it is essential that active insulin be accurately tracked. InPen, the first FDA-cleared, Stage 4 Smart Insulin Pen, is able to do this based on a proprietary algorithm. Additionally, users are able to indicate if a dose labeled prime is actually therapeutic or vice versa.
Don’t forget the basics: Injection technique, site rotation, insulin quality
It is important to not assume an individual who has had diabetes for years knows how to inject correctly. Ask individuals to periodically demonstrate how they inject. Problems with injection technique may be uncovered and corrected. Even in a virtual visit, the camera can be used to demonstrate correct insulin injection technique.
Also important is proper site rotation. Per ADA standards, patients using insulin should have an examination of insulin injection/infusion sites on a routine basis at least annually and if there are clinical issues related to insulin delivery (8). Research indicates that ~65% of individuals using insulin have lipohyperystrophy (9). Clinicians should also be sure to discuss how individuals are storing their extra insulin cartridges, pens and basal insulin and ensure individuals or keeping track of insulin expiration dates. With InPen, once a cartridge is inserted, the smart insulin pen will detect and alert the user when the cartridge has exceeded 28 days. It will also alert if the pen and cartridge has been exposed to unsafe temperatures.
To be successful in their glucose regulation, many people on intensive insulin therapy use carbohydrate counting, which involves measuring the carbohydrate content of the meal to calculate the exact insulin dose needed to maintain optimal postprandial glycemia. Making sure individuals have resources such as access to food data bases is helpful. In addition to dosing accurately, bolus insulin injection must be timed appropriately before the meal to avoid post-meal glucose spikes (Slattery, 2017). The insulin-to-carbohydrate ratio and correction factor for hyperglycemia are both individualized to one’s insulin sensitivity. These ratios may vary throughout the day, depending on meal timing and other factors, and is frequently more variable in pediatric populations due to their erratic eating habits, physical activity, and changing metabolism throughout development. Matching carbohydrate intake and the insulin requirement requires both accurate and precise delivery of insulin to address metabolic needs, minimize glycemic variability, and optimize glycemia. Smart Insulin Pens facilitate calculation of more exact bolus doses for meals and corrections, and these doses may be more effectively delivered using pen devices such as InPen capable of delivering precise half-unit increments.
InPen now offers dose calculator support including active insulin tracking for those on a simpler (but less precise) fixed dose insulin regimens, those who are adjusting their dose based on the relative size of their meal and also for those who count carbohydrates (11). Now across the full spectrum of intensive insulin therapy, individuals are able to know more precisely how much to dose at meals and for corrections due to accurate active insulin tracking. Figure 1, illustrates the math required to correctly calculate active insulin as well as calculate a mealtime insulin dose.
Conclusion: Precision Insulin Management Matters
We have discussed important considerations for precision insulin management:
- Determining the best method of insulin delivery for the individual
- Calculating and fine-tuning precise insulin therapy settings (based on integrated data reports)
- Precise dose delivery with insulin pens offering half-unit dose increments
- Priming and prime and therapeutic dose differentiation
- Assuring correct insulin injection technique, rotation of sites and storage of insulin
- Accurate, customized dose calculators for both meal and correction doses with objective active insulin tracking
Insulin pens have shown a positive impact on the health-related quality of life with less frequent and less severe episodes of hypoglycemia. Outcomes such as treatment satisfaction, ease-of-use, discreetness, convenience and flexibility, injection pain, and patient preference all favor the use of insulin pens. Insulin pens with half unit dose accuracy are critical for those who need stringent glycemic control, as they deliver more accurate and precise doses. Half-unit insulin pens are also evolving with technological advances such as the stage 4 smart insulin pen, InPen linked by Bluetooth® to a smart phone application that automatically records doses and incorporates a dose calculator and optional dose reminders to support precise insulin management.
Here’s to precise insulin management with Smart Insulin Pens!
About the Author
Janice MacLeod, MA, RD, CDCES, FADCES
Head of Clinical Advocacy, Companion Medical
Janice leads clinical advocacy at Companion Medical partnering with professional organizations and thought leaders in diabetes, digital health and practice transformation to establish smart insulin pens as a standard of care for individuals on injection therapy. Previously Janice served as the Director, Clinical Innovation for Welldoc and at Johnson & Johnson Diabetes Care in a variety of roles including as Clinical Affairs Manager, and as Senior Medical Science Liaison. Janice has spent many years in clinical practice as a diabetes dietitian and certified diabetes care & education specialist at University of Maryland in Baltimore, MD and Carilion Health System in Roanoke, VA. Janice has served as both author and editor for multiple publications, contributed to book and curriculum manuals on diabetes, and has developed numerous continuing education programs and presentations in the areas of diabetes nutrition, glucose monitoring, digital health, and practice transformation.