Introduction to Multi-Hormone AID Systems

The next generation of Artificial Pancreas technology, Multi-Hormone AID systems, is poised to revolutionize glucose management by integrating glucagon alongside insulin. This evolution marks a significant shift from Hybrid Closed-Loop (HCL) to Fully Closed-Loop operation, providing an active mechanism to prevent hypoglycemia [1].

Key Innovations

• Stable Glucagon: The development of Dasiglucagon and non-aqueous formulations has addressed the historical issue of glucagon instability in pumps, which previously led to fibrillation and clogging [2].
• Advanced Algorithms: A transition from traditional carb-counting methods to more sophisticated approaches, such as "meal announcement" or fully autonomous meal detection, enhances the system's ability to predict and respond to glucose fluctuations [3].

Major Players

• Inreda Diabetic (Netherlands): Notably, Inreda Diabetic has achieved the distinction of being the first to receive CE marking for a dual-hormone system, paving the way for commercialization in Europe [4].
• Beta Bionics (USA): Beta Bionics is actively developing the iLet, a dual-hormone system, with the insulin-only version already commercially available [5].

Critical Issues and Considerations

Despite the promise of Multi-Hormone AID systems, several challenges must be addressed:

• Complexity: The requirement for two infusion sites or the use of dual-lumen catheters adds complexity to the system, potentially impacting user adherence and satisfaction [6].
• Physiological Limitations: The effectiveness of glucagon can be compromised in scenarios where liver glycogen is depleted, such as after alcohol consumption or periods of exhaustion, highlighting the need for comprehensive user education [7].
• Economic Factors: The introduction of a second hormone significantly increases the recurring costs associated with these systems, which could affect accessibility for potential users [8].

Conclusion

Multi-Hormone AID systems represent a significant advancement in the management of glucose levels, offering enhanced control and reduced risk of hypoglycemia. However, addressing the challenges associated with complexity, physiological limitations, and cost will be crucial for the widespread adoption of these technologies.