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03-08-2021 | Immunotherapy | News

Anti-IL-21, liraglutide combination may warrant further investigation for early type 1 diabetes

Author: Claire Barnard


medwireNews: Phase 2 study results suggest that add-on treatment with an anti-interleukin (IL)-21 antibody plus liraglutide could preserve endogenous insulin secretion in people with recent-onset type 1 diabetes.

The researchers explain that the IL-21 antibody provides “low-grade and transient immunomodulation,” while the glucagon-like peptide (GLP)-1 receptor agonist liraglutide improves β-cell function, and they hypothesized that the combination of both agents “could enable β-cell survival with a reduced risk of complications compared with traditional immunomodulation.”

For the trial, 307 adults aged an average of 28.4 years with a recent (≤20 weeks) diagnosis of type 1 diabetes and a peak C-peptide concentration of at least 0.2 nmol/L were randomly assigned to receive 54 weeks of treatment with anti-IL-21 plus liraglutide, either treatment alone, or placebo.

Anti-IL-21 was given intravenously at a dose of 12 mg/kg every 6 weeks, while liraglutide was self-administered once daily as subcutaneous injections, with a target dose of 1.8 mg. All treatments were given alongside a treat-to-target insulin regimen.

Thomas Pieber (Medical University of Graz, Austria) and co-investigators report that participants in the combination therapy group experienced a significantly smaller decrease in mixed-meal tolerance test (MMTT)-stimulated C-peptide levels from baseline to week 54 than those given placebo, with reductions of 10% and 39%, respectively.

These findings suggest that the combination “was significantly better than placebo at preserving endogenous insulin secretion,” say the researchers, noting that the effect “was accompanied by nearly complete maintenance of fasting baseline C-peptide secretion and a reduction in the need for exogenous insulin by almost a third.”

They say that the benefit of combination therapy “seemed to be more pronounced” in people with lower C-peptide levels (≤0.6 nmol/L) at baseline, “possibly reflecting the beneficial effect of anti-IL-21 in preserving the remaining β-cell function.”

For participants given monotherapy, the decreases in MMTT-stimulated C-peptide levels were numerically smaller among those given anti-IL-21 (25 vs 39%) or liraglutide (32 vs 39%) versus placebo, but the between-group differences did not reach statistical significance.

The trial included a 26-week observation period after treatment cessation at week 54, and the team remarks that the benefits of treatment “diminished rapidly” after this time, “as the ongoing autoimmune process presumably resumed.”

In the safety analysis, the investigators say that the adverse event (AE) profiles were consistent with a previous report on anti-IL-21 and the established safety profile of GLP-1 receptor agonists in type 2 diabetes. The most frequently reported AEs in the combination group were nausea (25%) and nasopharyngitis (23%).

Taken together, the phase 2 study results “suggest that this combination has the potential to offer a novel and valuable disease-modifying therapy for patients with recently diagnosed type 1 diabetes,” conclude Pieber and team in The Lancet Diabetes & Endocrinology.

They add that “the efficacy and safety need to be further investigated in a phase 3 programme,” and “[f]urther research is warranted to explore the patient subgroups most likely to benefit” from combination therapy.

medwireNews is an independent medical news service provided by Springer Healthcare Ltd. © 2021 Springer Healthcare Ltd, part of the Springer Nature Group

Lancet Diabetes Endocrinol 2021; doi:10.1016/S2213-8587(21)00019-X


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This video has been developed through unrestricted educational funding from Abbott Diabetes Care.

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