Can Early Intervention Preserve β-Cell Function in Recently Diagnosed Type 1 Diabetes?

A woman discusses with her doctor about possibilities for diabetes treatment in a well lit medical facility.
Investigators studied whether combining anti-interleukin-21 antibody with liraglutide could enable β-cell survival with a reduced risk of complications compared with traditional immunomodulation.

A combination treatment containing anti-interleukin-21 (IL-21) antibody and liraglutide was found to preserve β-cell functioning compared with placebo, according to the results of a study published in The Lancet Diabetes & Endocrinology.

Investigators conducted a multicenter, randomized, placebo-controlled, double-blinded, phase 2 trial throughout 17 countries between November 2015 and February 2019 that included people recently diagnosed with type 1 diabetes (T1D) to assess the efficacy of combined anti-IL-21 antibody and liraglutide. The researchers used the anti-IL-21 antibody for low-grade and transient immunomodulation and liraglutide to improve β-cell function and survival.

A total of 308 participants were randomly assigned to receive anti-IL-21 antibody plus liraglutide, anti-IL-21 antibody alone, liraglutide alone, or placebo. The primary outcome was the change in mixed meal tolerance test (MMTT)-stimulated C-peptide concentration at week 54 compared with baseline.  

Prior to initiation of treatment, the researchers measured autoantibodies against insulin, glutamic acid decarboxylase, zinc-transporter-8, and islet antigen-2, and monitored them via assays throughout the trial.

The researchers saw a statistically significant decrease in MMTT-stimulated C-peptide concentration in the patients with T1D who received the combination treatment compared with the placebo group that received traditional methods of immunomodulation (0.90, 10% decrease; estimated treatment ratio 1.48, 95% CI, 1.16-1.89; P =.0017). Reduction in glycated hemoglobin (HbA1c) was greater with all active treatments compared with placebo.

The rate of hypoglycemic events did not differ significantly between the active treatment groups and the placebo group; however, the liraglutide-only group demonstrated a lower rate of these events during treatment compared with placebo.

No episodes of diabetic ketoacidosis occurred. Four adverse events were reported: 1 death (which was deemed unrelated to the trial); 1 coma, 1 patient with pneumonia, and 1 patient with brain edema.

Limitations of this study included the duration of the treatment of only 1 year and the enrollment of patients who had only recently been diagnosed with T1D (within 20 weeks of trial enrollment).  Efficacy was not evaluated in patients with early-stage T1D, and safety beyond 80 weeks was not evaluated.

The authors concluded that “the combination of anti-IL-21 and liraglutide could preserve β-cell function in recently diagnosed [T1D]. The efficacy of this combination appears to be similar to that seen in trials of other disease-modifying interventions in [T1D], but with a seemingly better safety profile.”


Several authors of the study are employees of Novo Nordisk, which funded the study, and one author holds shares in the company.  Two authors hold a patent related to this work.  Please see the original reference for a full list of disclosures.


Von Herrath M, Bain SC, Bode B, et al. 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. Lancet Diabetes Endocrinol. 2021;9:212-224. doi:10.1016/S2213-8587(21)00019-X