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Dasiglucagon stable-glucagon infusion for bihormonal AID

Zealand Pharma (with Beta Bionics)

A soluble, pump-stable glucagon analog — already FDA-approved as the Zegalogue rescue injection — that Zealand Pharma and Beta Bionics tested as the continuous-infusion second hormone in the bihormonal iLet closed loop. Early home-use data showed strong glucose control with very little hypoglycemia, but the planned pivotal trial never ran: in 2024 the partnership ended and Beta Bionics moved to a different pump-stable glucagon, leaving dasiglucagon's dual-hormone path shelved.

On the horizonModerate evidencedual-hormoneglucagonfully-closed-loop

The scorecard

Hypo protection80

Adding dasiglucagon to the iLet kept time below 54 mg/dL very low (median ~0.2-0.3% vs 0.6% insulin-only) — an active brake against lows insulin-only loops lack.

Time in range72

In Phase 2 home use, 90% on the bihormonal iLet hit mean CGM <154 mg/dL vs 50% insulin-only; the pivotal HbA1c-superiority trial was never completed.

Automation level80

Designed for the fully-closed iLet, which doses all insulin (and glucagon) from body weight alone with no carb counting — only meal-size announcements.

Maturity40

The molecule is approved and proven pump-stable in aqueous solution, but as a continuous-infusion second hormone it stalled at Phase 2; the Zealand-Beta Bionics program ended in 2024.

Low burden45

A second hormone means a second reservoir, more consumables, and a larger device than an insulin-only patch or pump.

Access & cost20

No bihormonal product ships: the iLet is sold insulin-only, and the dasiglucagon dual-hormone configuration is not available anywhere.

As with AID systems, glycemic criteria reflect the levels achieved in real-world or trial Type 1 use rather than the improvement over baseline, and Type 2 diabetes data is not used to score a Type 1 system.

The full picture

A bihormonal artificial pancreas delivers two hormones instead of one: insulin to bring glucose down, and glucagon to push it back up. Glucagon is the body's natural defense against a low, so giving a closed loop access to it provides an active "brake" that an insulin-only system simply does not have — letting the algorithm dose insulin more assertively without fear of overshooting into hypoglycemia.1

The catch has always been chemistry. Native glucagon is unstable in water — it clumps and forms fibrils within hours — which is why traditional rescue glucagon came as a powder you had to mix right before injecting.2 Dasiglucagon is a re-engineered glucagon analog that stays soluble and stable in a ready-to-use aqueous solution.3 That single property is what makes it a candidate to sit in a pump reservoir and be infused continuously. It is already approved: the U.S. FDA cleared it as Zegalogue on 22 March 2021 for severe hypoglycemia in people with diabetes aged 6 and older, as a pre-filled rescue auto-injector or syringe.43 In Phase 3 rescue trials it raised glucose about as fast as old reconstituted glucagon — median time to recovery roughly 10 minutes versus 30–40 minutes for placebo — with nausea and vomiting the main side effects.567

For the closed loop, Zealand Pharma partnered with Beta Bionics, whose iLet system doses all insulin automatically from a person's body weight with no carb counting — only a "small / medium / large" meal tap.8 In a home-use study, the bihormonal iLet using dasiglucagon was compared with the insulin-only version: 90% of people on the bihormonal system reached a mean CGM glucose below 154 mg/dL versus 50% on insulin-only, while time spent dangerously low (under 54 mg/dL) stayed minimal in both — a bihormonal median of about 0.2% (0.3% mean in the press release) versus 0.6% insulin-only.910 On the strength of that, the companies announced a planned pivotal program of roughly 350 adults and 350 children testing whether the dasiglucagon bihormonal iLet beat the insulin-only iLet on HbA1c at 26 weeks.10

That pivotal trial never ran. The iLet ultimately reached the market insulin-only, FDA-cleared in May 2023.8 In 2024 the strategy shifted: Beta Bionics signed an exclusive deal with Xeris (May 2024) to develop a different pump-stable glucagon for its dual-hormone pump, and the Zealand–Beta Bionics dasiglucagon collaboration was wound down later that year.1112 So the molecule is proven and approved as a rescue drug, and it proved the concept of stable glucagon in a closed loop — but its specific dual-hormone-pump track is, for now, shelved.

Device burden is real: two hormones means two reservoirs, more consumables, and a bulkier device than a single-hormone patch.1 Maturity and access: dasiglucagon is widely available as a rescue injection, but there is no bihormonal product you can buy that uses it.4

What's coming: the dual-hormone goal lives on, but the glucagon has changed. Beta Bionics is now developing the bihormonal iLet around the Xeris XeriSol glucagon rather than dasiglucagon.1113 Dasiglucagon itself continues in other settings — a mini-dose pen for exercise- and post-bariatric hypoglycemia, and Phase 3 work in congenital hyperinsulinism — keeping a stable, approved glucagon analog on the shelf should a future closed loop want it.10

References

  1. Infante M, Baidal DA, Rickels MR, et al. Dual-hormone artificial pancreas for management of type 1 diabetes: Recent progress and future directions. Artificial Organs (2021). According to PubMed, PMID 34263961. https://doi.org/10.1111/aor.14023 ↩ ↩2

  2. Li S, Hu Y, Tan X, et al. Evaluating dasiglucagon as a treatment option for hypoglycemia in diabetes. Expert Opinion on Pharmacotherapy (2020). According to PubMed, PMID 32267182. https://doi.org/10.1080/14656566.2020.1747432 ↩

  3. Blair HA. Dasiglucagon: First Approval. Drugs (2021). According to PubMed, PMID 34047955. https://doi.org/10.1007/s40265-021-01531-z ↩ ↩2

  4. Zealand Pharma. Zealand Pharma Announces FDA Approval of Zegalogue (dasiglucagon) injection, for the Treatment of Severe Hypoglycemia in People with Diabetes. GlobeNewswire (22 March 2021). https://www.globenewswire.com/news-release/2021/03/22/2197267/0/en/Zealand-Pharma-Announces-FDA-Approval-of-Zegalogue-dasiglucagon-injection-for-the-Treatment-of-Severe-Hypoglycemia-in-People-with-Diabetes.html ↩ ↩2

  5. Pieber TR, Aronson R, Hövelmann U, et al. Dasiglucagon—A Next-Generation Glucagon Analog for Rapid and Effective Treatment of Severe Hypoglycemia: Results of Phase 3 Randomized Double-Blind Clinical Trial. Diabetes Care (2021). According to PubMed, PMID 35239971. https://doi.org/10.2337/dc20-2995 ↩

  6. Battelino T, Tehranchi R, Bailey T, et al. Dasiglucagon, a next-generation ready-to-use glucagon analog, for treatment of severe hypoglycemia in children and adolescents with type 1 diabetes: Results of a phase 3, randomized controlled trial. Pediatric Diabetes (2021). According to PubMed, PMID 33934456. https://doi.org/10.1111/pedi.13220 ↩

  7. Heller S, Battelino T, Bailey TS, et al. Integrated safety and efficacy analysis of dasiglucagon for the treatment of severe hypoglycaemia in individuals with type 1 diabetes. Diabetes, Obesity & Metabolism (2023). According to PubMed, PMID 36692230. https://doi.org/10.1111/dom.14987 ↩

  8. Beta Bionics. Beta Bionics Announces FDA Clearance and Commercialization of the iLet Bionic Pancreas. Beta Bionics investor news (22 May 2023). https://investors.betabionics.com/news-releases/news-release-details/beta-bionics-announces-fda-clearance-and-commercialization-ilet ↩ ↩2

  9. 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). According to PubMed, PMID 33906916. https://doi.org/10.2337/dc20-1086 ↩

  10. Zealand Pharma. Zealand Pharma Launches ZEGALOGUE (dasiglucagon) Injection and Advances Pipeline Programs Across Multiple Therapeutic Areas. GlobeNewswire (12 August 2021). https://www.globenewswire.com/news-release/2021/08/12/2279843/0/en/Zealand-Pharma-Launches-ZEGALOGUE-dasiglucagon-Injection-and-Advances-Pipeline-Programs-Across-Multiple-Therapeutic-Areas.html ↩ ↩2 ↩3

  11. Xeris Biopharma. Xeris Enters Into an Exclusive Worldwide Collaboration and License Agreement with Beta Bionics. Xeris Biopharma press release (May 2024). https://xerispharma.com/news-releases/news-release-details/xeris-enters-exclusive-worldwide-collaboration-and-license ↩ ↩2

  12. Fierce Pharma. Zealand's hypoglycemia drug suffers another FDA rejection tied to CDMO inspection (noting the October 2024 termination of the Zealand–Beta Bionics dasiglucagon partnership). Fierce Pharma (2024). https://www.fiercepharma.com/pharma/zealand-suffers-2nd-fda-rejection-hypoglycemia-drug-tied-cdmo-inspection ↩

  13. Drug Delivery Business News. Xeris, Beta Bionics collab on glucagon product for pumps (6 May 2024). https://www.drugdeliverybusiness.com/xeris-beta-bionics-collab-glucagon-pumps/ ↩

Coming soon

ETA · Pipeline — stalled at Phase 2; the Zealand-Beta Bionics dasiglucagon program ended in 2024 and the planned pivotal never ran

  • →Beta Bionics now developing the bihormonal iLet around Xeris XeriSol glucagon instead of dasiglucagon
  • →Dasiglucagon itself continues in other settings — a mini-dose pen for exercise- and post-bariatric hypoglycemia, and Phase 3 work in congenital hyperinsulinism