A year-long Dutch trial found that the dual-hormone Inreda AP 5 improved glucose control for adults using insulin injections, but offered little advantage over advanced pumps and proved difficult to keep using.
A year-long Dutch trial has found that a dual-hormone artificial pancreas can improve glucose control for adults with type 1 diabetes who rely on insulin injections, but it adds little for people already using advanced hybrid closed-loop pumps. The study, published in The Lancet Regional Health – Europe, also raises a more awkward question for the field: half the participants stopped using the system before the end of the trial, most of them within the first three months.
Researchers in the DARE trial followed 243 adults at 14 centres in the Netherlands. Participants aged 18 to 75 were split into two groups according to their treatment at the start: one group used multiple daily insulin injections with glucose monitoring, while the other was already using hybrid closed-loop technology, which automatically adjusts insulin delivery but still depends on meal announcements and carbohydrate counting. The new system, the Inreda AP 5, attempts a more complete form of automation by delivering both insulin and glucagon without user-driven meal boluses or exercise announcements.
That approach builds on earlier studies suggesting that dual-hormone systems can improve time spent in target glucose ranges and reduce hypoglycaemia. A meta-analysis published in recent years reported similar advantages across randomised trials, and smaller crossover studies have shown benefits overnight and during exercise. But those trials were short and often involved tightly controlled settings, leaving open the question of whether the technology could deliver sustained gains in everyday life. The DARE trial was designed to answer that question over 12 months.
For adults using injections, the answer was broadly positive. According to the trial report, time spent in the target glucose range rose by about four percentage points in the dual-hormone group, while remaining largely unchanged in those continuing usual care. The adjusted difference between groups was 8.3 percentage points, which the researchers said was roughly equivalent to almost two extra hours a day in range. Average long-term glucose levels also improved, and more than half of the participants using the dual-hormone system reached a glycated haemoglobin level below 7%, compared with a much smaller share in the control group. The biggest gains came overnight, when the dual-hormone system substantially improved glucose control without increasing sensor-measured low glucose.
The picture was far less convincing among people already on hybrid closed-loop pumps. In that cohort, the new system produced no meaningful overall improvement in time in range, although it did slightly improve overnight glucose control. The researchers said the benefit was too small to matter clinically, especially given the extra complexity of the device.
That complexity proved to be a central problem. Half of the participants assigned to the dual-hormone arm discontinued the system, with the highest drop-out rates occurring early in the study. Many cited device burden, dissatisfaction with glucose control, alarms, skin irritation and the practical strain of wearing two infusion sets and two sensors. The study also recorded nine severe hypoglycaemic episodes in the dual-hormone groups, versus two in usual care, although no cases of diabetic ketoacidosis occurred and investigators reported no clear signal of harm from long-term glucagon exposure.
The trial was complicated by an unexpected change in glucagon supply before enrolment began. Novo Nordisk’s planned formulation was no longer available, forcing investigators to switch to another product and issue software updates during the study to adapt the system. Some participants did not receive the later update, and the researchers suggested that this may have blunted performance and contributed to both the modest benefit and the high discontinuation rate. On that reading, the technology remains promising but not yet ready for routine use as a truly hands-off artificial pancreas.
Disclaimer: This content is for informational purposes only and is not intended to be a substitute for professional medical judgment, advice, diagnosis, or treatment.
