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Phase 2CompletedNCT02443155

Anti-IL-21 plus liraglutide in recent-onset T1D

What this study tests

Completed phase 2 trial of an immune therapy combined with liraglutide. It found a C-peptide preservation signal during treatment; the development program was subsequently discontinued.

Editorial review: . What was checked and what remains uncertain.

Registry checked: 2026-09-16. Registry’s own update: 2021-04-09.

Latest dated source in the citation list: 2021-03-01. This is the source’s date, not a new review of every claim.

Trial status, labels and access can change between reviews.

Full sources ↓Full discussion ↓Report an issue →

Evidence at a glance

Who can enter the study?
Adults aged 18–45, diagnosed within 20 weeks, with residual C-peptide and islet autoantibodies. The protocol excluded pump use and insulin doses above 1 unit/kg/day. Enrollment is closed; these are key criteria, not the full eligibility list. 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
Of 308 randomized participants, 307 received treatment and entered the full analysis and safety sets. C-peptide declined by 10% with combination treatment versus 39% with placebo at week 54 (estimated treatment ratio 1.48, 95% CI 1.16–1.89; P=0.0017). Monotherapy comparisons were not significant. Effects diminished after treatment stopped.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: United States, European Union, United Kingdom, Canada, Other regions. 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 this trial’s review notes for the checks completed and what remains unresolved. Planned endpoints and completion dates are not results.

Research status alone does not establish approval, clinical benefit or local availability. This record cites company or conference reports. Those sources may describe interim findings; their source type is shown in the source list.

Primary endpoints

  • Ratio to baseline of stimulated C-peptide area under the curve during a four-hour mixed-meal test at week 54.

The full picture

Study and population

This four-group trial randomized 308 adults, 77 per group, to the combination, either treatment alone, or placebo. Participants had recent-onset T1D and remaining insulin production. One randomized participant never received treatment; 307 entered the full analysis and safety sets.1 The registry reports study completion on 27 February 2019 and posted results.2

Benefit and limits

At week 54, stimulated C-peptide declined by 10% with the combination and 39% with placebo (treatment ratio 1.48, 95% CI 1.16–1.89; P=0.0017). Neither monotherapy comparison was significant. HbA1c differences versus placebo were also not significant. The effect diminished during the 26 weeks after treatment stopped.1

Harms

Gastrointestinal events were common. No DKA occurred. One participant in the liraglutide-alone group died following hypoglycemic coma, pneumonia and brain edema; investigators considered these events unlikely to be related to treatment. A trial of this size cannot establish rare-event safety.1

Program status

Novo Nordisk reported discontinuing the anti-IL-21 program after assessing its regulatory path in the third quarter of 2020. That commercial decision should not be relabeled a failed primary endpoint. The combination remains a historical investigational approach, with no current T1D treatment approval established here.3

References

  1. Anti-interleukin-21 antibody and liraglutide for the preservation of β-cell function in adults with recent-onset type 1 diabetes: a randomised, double-blind, placebo-controlled, phase 2 trial. https://pubmed.ncbi.nlm.nih.gov/33662334/ ↩ ↩2 ↩3

  2. ClinicalTrials.gov. NCT02443155. Checked 16 September 2026. https://clinicaltrials.gov/study/NCT02443155 ↩

  3. Novo Nordisk financial results for the first nine months of 2020. https://www.novonordisk.com/content/dam/nncorp/global/en/investors/irmaterial/quarterly_financial_reports/2020/20201030_Q3-CA.pdf ↩

Sources

  1. [1]A Clinical Proof-of-principle Trial in Adult Subjects With Newly Diagnosed Type 1 Diabetes Mellitus Investigating the Effect of NNC0114-0006 and Liraglutide on Preservation of Beta-cell Function · registry — Protocol and registry status checked 16 September 2026.
  2. [2]Anti-interleukin-21 antibody and liraglutide for the preservation of β-cell function in adults with recent-onset type 1 diabetes: a randomised, double-blind, placebo-controlled, phase 2 trial · peer-reviewed · 2021-03-01
  3. [3]Novo Nordisk financial results for the first nine months of 2020 · manufacturer · 2020-10-30