Early lab and animal tests show that a new form of insulin could help prevent sudden drops in blood sugar. The modified insulin, called NNC2215, has a switch that can open and close in response to blood sugar. When blood sugar levels are high, the switch opens, and the insulin becomes more active, removing the sugar from the blood. When blood sugar levels decrease, the switch moves to a closed state, which stops the sugar being removed. This could help people with diabetes avoid sudden drops in blood glucose, which can be life-threatening.

A modified insulin that can prevent sudden drops in blood sugar is demonstrated in laboratory experiments and animal models, reported in a paper in Nature https://www.nature.com/articles/s41586-024-08042-3. This could provide a more flexible way to supplement insulin for individuals with diabetes and reduce sudden drops in blood glucose.

For some people with diabetes, supplementary insulin injections are needed to control blood glucose levels. Fluctuations in blood glucose levels are difficult to predict, making it hard to select the appropriate insulin doses. Even a slightly high dose can lead to hypoglycaemia (blood glucose levels decreasing too much), which can be life-threatening.

Rita Slaaby and colleagues present a modified form of insulin with activity that varies according to the levels of glucose in the blood. The molecule, named NNC2215, is equipped with a switch that can open and close in response to glucose. Under high glucose concentrations, the switch opens, and the insulin becomes more active, removing glucose from the blood. When glucose levels decrease, the switch moves to a closed state, which prevents glucose uptake.

Laboratory experiments showed that upon an increase in glucose concentration from 3 to 20 mM (approximately the fluctuation range experienced by individuals with diabetes), the NNC2215 insulin receptor affinity increased by 3.2-fold, validating its potential to respond to changes in blood glucose levels. In rat and pig models of diabetes, NNC2215 proved to be as effective as human insulin in lowering blood glucose. Its increased glucose sensitivity was shown to provide protection against hypoglycaemia in these animal subjects.

This modified insulin shows promise in preventing the sharp drops in glucose that can severely affect individuals with diabetes, especially during sleep. This could improve both long- and short-term complications associated with diabetes, the authors note.