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

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 (HbA_1c) 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.”

Disclosure

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.

Reference

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