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Phase 2/3CompletedNCT03840278

Bihormonal iLet Bionic Pancreas (insulin + glucagon) feasibility study

First-in-human home-use feasibility test of the dual-hormone iLet bionic pancreas, which adds automated micro-doses of a stable glucagon (dasiglucagon) on top of automated insulin to push back against lows. In 10 adults with type 1 diabetes, the bihormonal version met all engineering targets and roughly halved time spent in low glucose versus the insulin-only iLet while also raising time-in-range, supporting a move to larger pivotal trials.

Primary endpoints

  • iLet operational performance: CGM glucose reading capture rate (target at least 80%)
  • Drug-delivery channel availability for insulin and for glucagon (target at least 95%)
  • Ratio of cumulative delivered-to-attempted drug volume (target 95-105%)

Results so far

All 10 participants completed both arms. Both configurations met every prespecified engineering target. The bihormonal iLet cut median time below 54 mg/dL to 0.2% (vs 0.6% insulin-only) and median time below 70 mg/dL to 2.0% (vs 4.0%), while raising time-in-range (70-180 mg/dL) to 79% (vs 72%) and lowering mean glucose to 139 mg/dL (vs 149). A single prefilled dasiglucagon cartridge lasted the full 7 days (mean 0.35 mg/day). No severe hypoglycemia, no diabetic ketoacidosis, and no serious adverse events; one episode of vomiting in the bihormonal arm. Insulin leakage at the cartridge connector occurred in five instances and prompted a hardware redesign for the next-generation device.

The full picture

What was tested and why it matters

Most automated insulin systems can only do one thing about a falling glucose: cut back insulin. They can't actively raise glucose. The bihormonal iLet adds a second hormone — automated micro-doses of glucagon, the body's own "raise glucose" signal — so the system can push back against lows instead of just easing off insulin.1 This study was the first time the dual-hormone iLet was tested in people, and the first multi-day human use of dasiglucagon, a chemically stable glucagon analog that (unlike older glucagon) stays usable in a pump for days.2

The iLet itself is a purpose-built device: it reads a continuous glucose monitor (CGM) and runs a self-learning dosing algorithm that is set up using only the person's body weight, with no carb counting or manual dose settings.1

Who it's for

Adults with type 1 diabetes who already use a pump and CGM. The 10 participants ranged from 21 to 74 years old, with starting HbA1c levels from 5.7% to 10.6% — a deliberately wide range.3

Design

This was an open-label, random-order crossover home-use trial sponsored by Massachusetts General Hospital, with Beta Bionics (the iLet) and Zealand Pharma (dasiglucagon) as collaborators.4 Each person used the insulin-only iLet for 7 days and the bihormonal iLet (insulin lispro or aspart plus dasiglucagon at 4 mg/mL) for 7 days, in random order, at the same glucose target (110 mg/dL), with no restrictions on food or exercise.3 The registry lists it as a Phase 2/Phase 3 feasibility study.4 All 10 enrolled participants completed both arms.3

Key results

Both configurations hit every prespecified engineering target (CGM capture ~89-91%, drug channels available >99% of the time).3 Clinically, adding glucagon helped: median time below 54 mg/dL fell from 0.6% to 0.2%, and time below 70 mg/dL from 4.0% to 2.0%.3 Time-in-range (70-180 mg/dL) rose from 72% to 79%, and mean glucose dropped from 149 to 139 mg/dL.3 A single prefilled dasiglucagon cartridge lasted the whole week (mean 0.35 mg/day), with no infusion-site reactions or occlusions.3 Safety was reassuring — no severe lows, no ketoacidosis, no serious adverse events; one bihormonal-arm vomiting episode.3

What it means / what's next

The study showed the dual-hormone iLet works in real-world home use and can drive lows down further than insulin alone, while a practical liquid glucagon survives a week in the pump.3 Five insulin-leak events at the cartridge connector were traced to off-center septum piercing and prompted a hardware redesign for the next generation; the authors concluded the system was ready for much larger, longer pivotal trials.3

References

  1. Castellanos LE, Balliro CA, Sherwood JS, et al. Performance of the Insulin-Only iLet Bionic Pancreas and the Bihormonal iLet Using Dasiglucagon in Adults With Type 1 Diabetes in a Home-Use Setting. Diabetes Care (2021);44(6):e118-e120. https://doi.org/10.2337/dc20-1086 ↩ ↩2

  2. Castellanos LE, Balliro CA, Sherwood JS, et al. Diabetes Care (2021);44(6):e118-e120 (full text, PubMed Central PMC8247518). https://pmc.ncbi.nlm.nih.gov/articles/PMC8247518/ ↩

  3. Castellanos LE, Balliro CA, Sherwood JS, et al. Diabetes Care (2021);44(6):e118-e120 (results and Table 1). https://doi.org/10.2337/dc20-1086 ↩ ↩2 ↩3 ↩4 ↩5 ↩6 ↩7 ↩8 ↩9 ↩10

  4. The Bihormonal iLet Bionic Pancreas Feasibility Study. ClinicalTrials.gov, NCT03840278 (sponsor, collaborators, phase, design). https://clinicaltrials.gov/study/NCT03840278 ↩ ↩2