Inreda AP (dual-hormone)

The Inreda AP is the most advanced dual-hormone artificial pancreas in real-world use. It delivers two hormones — insulin to lower glucose and glucagon to raise it — and runs as a genuinely fully closed loop: no carb counting, no meal announcements, and no exercise input.¹ That full automation is possible precisely because the second hormone gives the algorithm an active brake. Insulin-only systems can only stop delivering insulin and then wait; glucagon lets the Inreda AP push glucose back up in real time, so its controller can run more aggressively without driving the user low.²

How the second hormone defends lows. When the device's sensors detect glucose falling, it delivers small doses of glucagon to mobilise stored glucose from the liver — a fast counter-regulatory response that mimics what a healthy pancreas does. In the 1-year real-world trial, median time below range was just 1.36% (well under the 4% safety target), and in an earlier randomized crossover study the system delivered glucagon automatically with no exercise or meal announcements.¹²

Trial outcomes. The pivotal evidence is a 1-year, eight-centre, single-arm trial in 79 adults in the Netherlands, published in The Lancet Digital Health (2024). Time in range rose from 55.5% before the trial to 80.3% at 12 months — roughly six extra hours per day in target.¹ Diabetes distress (PAID) fell from 30 to 10 and well-being (WHO-5) rose from 60 to 76.¹ An earlier randomized crossover trial in Diabetes Care found ~87% time in range on the closed loop versus ~54% on usual pump therapy.² A separate JAMA Surgery trial in people with no pancreas at all (after total pancreatectomy) showed the same pattern — higher time in range, near-zero hypoglycemia.³

The glucagon-stability challenge. Reconstituted glucagon (the device uses GlucaGen) is chemically unstable in solution and tends to aggregate, so there is no shelf-stable pre-filled cartridge yet — the user fills the glucagon reservoir by hand and replaces it every single day.⁴⁵ Solving this is the central formulation problem for all two-hormone systems; newer stable analogs (e.g. dasiglucagon) were developed specifically to fix it.⁵

Device burden. Two hormones mean roughly double the hardware: two infusion sets, two reservoirs, and two redundant CGM sensors (one drives therapy, one cross-checks it), all in a body-worn unit about 12 x 8 x 4 cm.⁴ Users in a qualitative study described real benefits (better glucose, "feeling more like a person without diabetes") but flagged the daily glucagon swap, multiple components, and alarms as the main hassles — and these drove most discontinuations.⁶

Maturity and access. The current generation, AP5, is CE-marked under the EU Medical Device Regulation, the bar for genuine clinical use.⁷ But access is narrow: it is available essentially only in the Netherlands, through Inreda-run projects and limited insurer coverage, with no FDA clearance and no broad commercial EU sale.⁴⁷ We mark it available as a regional (EU) deployment, not a globally purchasable product.

What's coming. Inreda is developing the next-generation AP6, aimed at a smaller, lighter device.⁷ The field-wide priorities are a stable, pre-fillable glucagon to end the daily-refill burden, pediatric use (a youth/adolescent study is underway), and broader reimbursement to move beyond a single country. The Inreda AP is the clearest existence proof that fully closed, no-announcement automation is real — the remaining work is shrinking the box and stabilising the second hormone.¹⁵

References

1. van Bon AC, Blauw H, Jansen TJP, et al. Bihormonal fully closed-loop system for the treatment of type 1 diabetes: a real-world multicentre, prospective, single-arm trial in the Netherlands. The Lancet Digital Health (2024). According to PubMed (PMID 38443309). https://doi.org/10.1016/S2589-7500%2824%2900002-5 ↩ ↩² ↩³ ↩⁴ ↩⁵

2. Blauw H, Onvlee AJ, Klaassen M, van Bon AC, DeVries JH. Fully Closed Loop Glucose Control With a Bihormonal Artificial Pancreas in Adults With Type 1 Diabetes: An Outpatient, Randomized, Crossover Trial. Diabetes Care (2021). According to PubMed (PMID 33397767). https://doi.org/10.2337/dc20-2106 ↩ ↩² ↩³

3. van Veldhuisen CL, Latenstein AEJ, Blauw H, et al. Bihormonal Artificial Pancreas With Closed-Loop Glucose Control vs Current Diabetes Care After Total Pancreatectomy: A Randomized Clinical Trial. JAMA Surgery (2022). According to PubMed (PMID 36069928). https://doi.org/10.1001/jamasurg.2022.3702 ↩

4. Inreda Diabetic. Frequently Asked Questions (device dimensions 11.9 x 7.7 x 3.7 cm; GlucaGen glucagon manually filled and changed daily; two Guardian sensors with redundancy; Netherlands pilot projects). Inreda Diabetic (accessed 2026). https://inredadiabetic.nl/en/faq/ ↩ ↩² ↩³

5. Blauw H, Keith-Hynes P, Koops R, DeVries JH. A Review of Safety and Design Requirements of the Artificial Pancreas. Annals of Biomedical Engineering (2016). According to PubMed (PMID 27352278). https://doi.org/10.1007/s10439-016-1679-2 ↩ ↩² ↩³

6. Nefs G, Jansen TJP, Klaassen M, et al. User Experiences of a Bihormonal Fully Closed-Loop System Among Adults with Type 1 Diabetes in a Real-World Setting: A Qualitative Analysis. Diabetes Technology & Therapeutics (2025). According to PubMed (PMID 41055383). https://doi.org/10.1177/15209156251383522 ↩

7. Inreda Diabetic. Discover the AP (AP5 CE approved under MDR; AP6 under development; bi-hormonal fully closed loop). Inreda Diabetic (accessed 2026). https://www.inredadiabetic.nl/en/discover-the-ap/ ↩ ↩² ↩³