Can Bi-Hormonal Systems Finally Eliminate Severe Hypoglycemia?

Many people with type 1 diabetes live with the constant fear of blood glucose dropping too low. Even today’s most advanced automated insulin delivery systems cannot actively raise glucose once levels begin to fall. Instead, they can only reduce or suspend insulin delivery. A dual-hormone artificial pancreas system changes that approach by delivering both insulin and glucagon, allowing the system to prevent hypoglycemia before it becomes dangerous. Recent studies suggest these dual-hormone systems may represent one of the most important advances in diabetes management for individuals with severe hypoglycemia unawareness. However, questions about long-term use, cost, and accessibility remain.

Table of Contents

• Why severe hypoglycemia remains a major challenge
• How a dual-hormone artificial pancreas system works
• What the latest clinical trials show
• Will bi-hormonal systems become the next standard of care?
• Conclusion
• Frequently Asked Questions

Why Severe Hypoglycemia Remains a Major Challenge

Despite remarkable advances in continuous glucose monitoring (CGM) and hybrid closed-loop insulin pumps, severe hypoglycemia continues to affect many people with type 1 diabetes. Individuals with impaired awareness of hypoglycemia are especially vulnerable because they may not recognize symptoms until glucose levels become dangerously low.

Current commercial hybrid closed-loop automated insulin delivery systems predict falling glucose and respond by decreasing or suspending insulin infusion. While this strategy reduces many hypoglycemic events, it has an important limitation. Insulin already circulating in the body continues working for several hours. Therefore, simply stopping insulin may not prevent glucose from continuing to decline.

As a result, patients often must consume carbohydrates to avoid severe hypoglycemia. This requirement can interrupt sleep, exercise, work, and daily activities. Moreover, recurrent episodes increase anxiety and reduce quality of life.

According to the American Diabetes Association, severe hypoglycemia remains one of the most significant barriers to achieving recommended glycemic targets because both patients and clinicians may intentionally accept higher glucose levels to reduce risk. Consequently, a therapy capable of actively preventing hypoglycemia could improve both safety and overall glucose control.

How a Dual-Hormone Artificial Pancreas System Works

A dual-hormone artificial pancreas system builds on today’s automated insulin delivery (AID) technology by adding a second hormone: glucagon. Instead of relying solely on insulin adjustments, the system continuously evaluates CGM data and determines whether insulin, glucagon, or neither hormone should be delivered.

Stable liquid glucagon analogs, particularly dasiglucagon, have made this approach practical. Traditional glucagon formulations required immediate mixing before use because they degraded rapidly. However, newer stable formulations remain effective in pump reservoirs for extended periods, making continuous automated delivery possible.

When glucose begins trending downward, the algorithm may administer tiny doses of glucagon before hypoglycemia develops. Consequently, glucose levels can stabilize without requiring carbohydrate intake in many situations.

Modern closed-loop control algorithms also learn from previous glucose patterns and insulin sensitivity. Therefore, the system continually adapts to meals, physical activity, illness, and daily routines. As software improves, prediction accuracy continues to increase.

Patients who experience frequent nocturnal hypoglycemia or hypoglycemia unawareness may benefit the most because these individuals often require rapid intervention before symptoms appear. Those interested in emerging diabetes technologies can also explore related clinical updates on Diabetes In Control.

What the Latest Clinical Trials Show

Recent randomized crossover trials evaluating bi-hormonal automated insulin delivery systems have produced encouraging results. Multiple studies demonstrate increased time in target glucose range while significantly reducing both mild and severe hypoglycemia.

Investigators studying insulin plus dasiglucagon systems consistently report fewer episodes of glucose below 70 mg/dL compared with insulin-only automated delivery. Furthermore, overnight glucose control often improves because glucagon can correct falling glucose without requiring patients to wake and consume carbohydrates.

Several trials have also demonstrated improvements in time below range (TBR), one of the key CGM performance metrics. Importantly, these benefits generally occur without increasing hyperglycemia or HbA1c levels.

Exercise represents another situation where automated insulin delivery can struggle. Physical activity increases insulin sensitivity and often produces unpredictable glucose declines. Because glucagon can rapidly stimulate hepatic glucose release, automated dosing may substantially reduce exercise-associated hypoglycemia.

Nevertheless, researchers continue evaluating several practical considerations. These include pump complexity, dual-reservoir maintenance, glucagon stability during prolonged use, algorithm optimization, and overall device cost. Long-term real-world studies will help determine whether these systems maintain their advantages outside carefully controlled research environments.

Healthcare providers can also help identify appropriate candidates for advanced diabetes technologies through resources available at Healthcare.pro.

Will Bi-Hormonal Systems Become the Next Standard of Care?

Evidence supporting dual-hormone automated insulin delivery technology continues to grow. Although current insulin-only systems have dramatically improved diabetes care, they still cannot fully mimic the body’s natural balance between insulin and glucagon.

A bi-hormonal approach more closely resembles normal pancreatic physiology. As a result, patients may experience greater confidence during sleep, exercise, travel, and other situations where hypoglycemia risk traditionally increases.

However, widespread adoption will depend on several factors beyond clinical performance. Manufacturers must demonstrate long-term reliability, affordable pricing, simplified maintenance, and favorable insurance coverage. Regulatory approval of additional stable glucagon formulations may also expand treatment options.

Artificial intelligence will likely play an increasing role as algorithms become better at predicting glucose trends using larger datasets and personalized learning. Future systems may eventually require even less user input while delivering more precise hormone dosing.

If these developments continue, dual-hormone technology could represent the next major evolution in automated diabetes management, especially for individuals who continue experiencing severe hypoglycemia despite current hybrid closed-loop systems.

Conclusion

Dual-hormone automated insulin delivery represents an important step toward more physiologic diabetes management. By combining insulin with stable glucagon analogs such as dasiglucagon, these systems actively prevent hypoglycemia instead of simply reducing insulin delivery. Clinical trials consistently demonstrate meaningful reductions in hypoglycemia while maintaining excellent overall glucose control. Although questions remain regarding cost, long-term durability, and access, the technology shows considerable promise for patients with severe hypoglycemia unawareness and may redefine the future of automated insulin delivery.

Frequently Asked Questions

What is a dual-hormone artificial pancreas system?

It is an automated diabetes management system that delivers both insulin and glucagon based on continuous glucose monitor readings.

Why is glucagon added to the system?

Glucagon raises blood glucose when levels begin falling, allowing the system to prevent hypoglycemia before it becomes severe.

What is dasiglucagon?

Dasiglucagon is a stable glucagon analog that can remain in pump reservoirs for extended periods, making continuous automated delivery possible.

Who may benefit most from these systems?

People with type 1 diabetes who experience severe hypoglycemia, nocturnal hypoglycemia, or hypoglycemia unawareness may benefit the most.

Are dual-hormone systems commercially available?

Several systems remain under clinical evaluation or regulatory review, although ongoing research continues to support their potential future use.

Disclaimer: This content is not medical advice. For any health issues, always consult a healthcare professional. In an emergency, call 911 or your local emergency services.