NNC0363-1063: first-in-human glucose-sensitive insulin in type 1 diabetes
What this study tests
Novo Nordisk's glucose-sensitive insulin (GSI) candidate, tested in healthy participants and in people with type 1 diabetes. Three parts: single ascending dose, a proof-of-principle part, and a multiple-dose meal test. This tests a newer candidate; an earlier glucose-responsive insulin, MK-2640, was already studied in people with T1D. It completed in March 2026 and no results have been posted, so no human glucose-response curve is public.
Editorial review: .
Registry checked: 2026-09-17. Registry’s own update: 2026-04-09.
Most recent recorded citation date: 2024-11-12. Only explicit date metadata is included; an undated citation may be newer. This does not mean every claim was reviewed on that date.
Trial status, labels and access can change between reviews. How we review the evidence · How to read the evidence
Evidence at a glance
- Who can enter the study?
- Adults 18-64. Part 1A enrolled healthy participants; Parts 1B, 2 and 3 enrolled adults diagnosed with type 1 diabetes at least one year earlier. BMI 18.5-29.9. Registered eligibility ↗Enrollment criteria describe who may enter. They do not establish who was analyzed or the denominator for a reported result.
- Reported benefit and results
- None posted. The study completed on 18 March 2026 with 117 participants enrolled; ClinicalTrials.gov shows no results and Novo Nordisk has not published a human glucose-response curve for this molecule.Read the result sources and their limitations →
- Important harms
- Read the reported results, safety discussion and original sources. A separate harms summary is not available; this does not establish safety.
- Research access and approval
- Study regions: European Union. A trial listing does not establish product approval or current recruitment at a particular site. Check the study’s current entry requirements.
- What remains uncertain?
- Read the full discussion and original sources for study limitations. Planned endpoints and completion dates are not results.
Research status alone does not establish approval, clinical benefit or local availability.
Primary endpoints
- Part 1 (single ascending dose): number of adverse events
- Part 2 (proof of principle): apparent serum clearance of NNC0363-1063 after a single dose
- Part 3 (meal test): area under the plasma glucose concentration-time curve at steady state
The full picture
This is the study that makes "smart insulin has reached humans" a true statement rather than an aspiration — and it is also a good illustration of how little that statement currently buys.
What was tested. NNC0363-1063 is Novo Nordisk's clinical glucose-sensitive insulin. It is not NNC2215, the molecular switch published in Nature in October 2024 — that compound remains animal-only. The two are frequently conflated because both are Novo's and both are "smart insulin"; they are different molecules at very different stages.
Design. Three parts, escalating in ambition: a single-ascending-dose part in healthy adults and then in adults with T1D; a proof-of-principle part measuring how quickly the drug clears; and a multiple-dose meal-test part measuring the glucose curve after eating. Comparators were placebo, insulin degludec and insulin detemir. A meal test is the first design here that could in principle show glucose-responsiveness doing something useful.
What we do not know. Everything that matters. The study completed in March 2026 and no results are posted. There is no published human glucose-response curve, no potency figure against human insulin, and no outpatient data. That gap is precisely the one that killed MK-2640: Merck's candidate looked excellent in dogs and minipigs and then failed to demonstrate glucose-dependent clearance in people with T1D.
Until a response curve is published, the honest summary is that the class has entered humans and has not yet been shown to work in them.
Earlier primary human evidence: Krug et al., clinical evaluation of MK-2640. Its glucose-dependent clearance result was negative; it still predates this candidate’s human study.
Sources
- [1]A Study Investigating Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Single and Multiple Doses of NNC0363-1063 in Healthy Participants and Participants With Type 1 Diabetes · Trial registry · 2024-11-12 — Phase 1, n=117, started 12 Nov 2024, completed 18 Mar 2026. Single site (Profil, Neuss, Germany). No results posted as of Aug 2026.