‘Smart Insulin’ Innovation Aims to Reduce Risk of Hypoglycemia

Michael Weiss and his fellow researchers have made significant progress in identifying a new type of medication that can regulate both insulin and glucagon in Type 1 diabetes patients. Credit:Tim Yates, IU School of Medicine

A team of scientists at the Indiana University School of Medicinehas discovered a groundbreaking way to regulate blood sugar levels using a lab-designed protein that combines the power of insulin and glucagon. The innovation could one day pave the way for a new treatment approach for people with Type 1 diabetes, offering more stable glucose control and reducing the risk of dangerous blood sugar lows.

A Dual-Action Molecule for Balanced Blood Sugar

The findings, published in ACS Pharmacology and Translational Science, showed that rats treated with the new hybrid protein experienced significant improvements in glucose regulation. The engineered molecule combines insulin, which lowers blood sugar, and glucagon, which raises it, into one dynamic system capable of adjusting to the body’s needs.

In people with Type 1 diabetes, the body’s immune system destroys the pancreatic cells that produce insulin, forcing patients to rely on synthetic insulin injections to control glucose levels. However, maintaining this balance is a daily challenge — both hyperglycemia (too much sugar) and hypoglycemia (too little sugar) can cause severe health complications or even be life-threatening.

Mimicking the Body’s Natural Balance

The new protein mimics how the liver naturally responds to insulin and glucagon, essentially creating an internal “smart switch.” This enables the liver to adjust its hormonal response depending on whether blood sugar levels are high or low.

“Our approach simplifies smart insulin design by exploiting the liver’s own mechanisms,” explained Dr. Michael A. Weiss, Distinguished Professor at IU School of Medicine and the study’s lead investigator. “If glucose is too high, insulin dominates. If it’s too low, glucagon takes over. This allows for more natural and safer blood sugar regulation.”

Weiss and his team have been working toward this goal for years, building on earlier research into glucose-responsive ‘smart insulins’. The current study marks an important step forward in simplifying that concept into a single, self-regulating molecule.

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More Stable, More Practical

In addition to its therapeutic benefits, the new insulin–glucagon hybrid demonstrated remarkable stability, remaining effective for several weeks without refrigeration. That feature could make it much easier to store, transport, and distribute, especially in regions with limited access to consistent refrigeration — a common challenge for traditional insulin therapies.

Toward a Smarter Future in Diabetes Care

Currently, many Type 1 diabetes patients must inject insulin and glucagon separately to avoid hypoglycemia, while also adjusting doses based on diet, stress, and activity levels. The new smart insulin could simplify this process dramatically, potentially requiring just a single injection per week or integration into insulin pump systems for continuous control.

Weiss noted that while the early results are promising, the research is still in its preclinical phase. Further studies, including human trials, will be needed before the hybrid medication can be approved for public use.

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