Glucose-Responsive Insulin Shows Promise in Preventing Hypoglycemia in Diabetes Management

A novel insulin with glucose-sensitive properties may soon offer individuals with diabetes a safer way to regulate blood sugar levels and avoid dangerous episodes of hypoglycemia. Detailed in a recent Nature publication, this insulin, known as NNC2215, is equipped with a “switch” that modulates insulin activity based on blood glucose levels, potentially marking a significant step forward in diabetes treatment.

A New Mechanism for Blood Sugar Control

Traditional insulin injections require precise dosing, but predicting blood glucose fluctuations can be challenging, especially for those with diabetes. An insulin dose slightly higher than needed can cause blood glucose to fall too low, leading to hypoglycemia, a potentially life-threatening condition. Researcher Rita Slaaby and colleagues have developed NNC2215, a modified form of insulin with a unique mechanism: it responds to high glucose levels by opening a “switch” that increases insulin activity to lower glucose. When glucose levels are low, the switch closes, thereby preventing unnecessary glucose uptake and minimizing the risk of hypoglycemia.

This responsive action was validated in laboratory experiments, where an increase in glucose concentration from 3 to 20 mM—the range typically experienced by people with diabetes—prompted a 3.2-fold increase in NNC2215’s insulin receptor affinity. In animal studies with diabetic rats and pigs, NNC2215 effectively reduced blood glucose levels and showed added protection against hypoglycemia, proving comparable in efficacy to human insulin.

Implications for Diabetes Care

This glucose-sensitive insulin could be particularly valuable for patients who experience frequent fluctuations in blood sugar, including during sleep when hypoglycemia risk is elevated and monitoring capabilities are limited. By adapting to blood glucose levels in real-time, NNC2215 may help patients achieve better glycemic control with less risk of dangerous drops, ultimately easing the burden of diabetes management.

Though further research is necessary to confirm NNC2215’s efficacy and safety in humans, these initial findings in animal models suggest that glucose-responsive insulin could be a transformative tool in diabetes care.