The future of insulin delivery (smart pens, infusers)

Abstract

Automated insulin delivery (AID) systems have seen significant progress toward fully closed-loop (FCL) systems, which seek to completely eliminate manual intervention for meal or exercise prompts, offering fully automated and personalized glycemic control.

Main approaches to AID systems

• Bihormonal systems. These represent a crucial step toward autonomous control, combining insulin with other hormones to mimic pancreatic physiology:

- Insulin + glucagon: A fully reactive system that does not require meal or exercise prompts, significantly improving IRR. However, it presents operational complexity as glucagon must be reconstituted and requires calibration of two sensors.

- Insulin + pramlintide: This uses this amylin analogue to improve postprandial control. Phase 2 studies show promising results, helping to mitigate post-meal glycemic excursions.

• Insulin-only systems. Although simpler, they face challenges due to delayed subcutaneous absorption and interstitial detection:

- Ultra-rapid insulins: These seek to accelerate action to better respond to glycemic variability, with a greater impact at breakfast and dinner.

- Intraperitoneal administration: This allows for faster action, greater hepatic uptake, and earlier glycemic detection than subcutaneous sensors.

- Advanced algorithms: The bolus priming system automatically detects unannounced meals based on the rate of glycemic rise, running every 5 minutes.

• DIY (Do-It-Yourself) systems. Loop, AndroidAPS, and Trio represent open innovation with algorithms like Super Micro Bolus, which improve postprandial control without manual boluses. The Food and Drug Administration (FDA) has begun approving open-source algorithms like Loop.

Smart Pens and Smart Caps

For patients not using closed-loop systems, connected pens and caps represent a promising solution. These devices integrate continuous glucose monitoring (CGM) data with insulin dose information:

• Types: Rechargeable pens and disposable pen caps.
• Functions: From data downloads to "smart" systems with therapeutic advice.
• Proven benefits: 6% increase in IRR, reduction in time with glucose >180 mg/dL, improved treatment adherence.
• Applications: They improve self-management, enable telemedicine, and are useful in institutional and clinical research settings.

Challenges of AID systems

• Postprandial monitoring: Mixed meals and the "pizza effect" remain challenges.
• Unplanned exercise: Requires adaptive algorithms combining heart rate, accelerometry, and CGM.
• Global accessibility: Ensure access regardless of geographic location or economic status.

AID systems promise to free people with diabetes from the stress of daily management, significantly improving metabolic control and quality of life.