medwireNews: Several therapies aimed at slowing the progression of early type 1 diabetes show promise in research presented at the virtual 80th ADA Scientific Sessions.
These include anti-interleukin (IL)-21 plus liraglutide; the CXCR1/2 inhibitor ladarixin; and the tumor necrosis factor α inhibitor golimumab. All three studies were preliminary, with the largest being a phase 2 trial involving 307 people.
The participants in this largest randomized trial, presented by Thomas Pieber (Medical University of Graz, Austria), were adults with newly diagnosed type 1 diabetes who were randomly assigned to one of four treatment groups. One group received intravenous anti-IL-21 every 6 weeks, to target IL-21–mediated inflammation related to the underlying disease process, and a second received liraglutide 1.8 mg/day, because glucagon-like peptide-1 receptor agonists are thought to reduce beta-cell stress and apoptotic cell death. The other two groups received both treatments or placebo, and all participants received insulin according to individual needs.
Beta-cell function based on C-peptide area under the curve after a mixed-meal tolerance test declined over the study in all treatment arms during the 54-week treatment period. However, at week 54 beta-cell function was significantly better with combination treatment versus placebo and versus liraglutide, by 48% and 33%, respectively, and there was a nonsignificant 20% improvement versus anti-IL-21 alone. Neither treatment alone produced a significantly greater preservation of beta-cell function versus placebo.
After an additional 26 weeks of observation, the positive effect of combination treatment had disappeared, and the liraglutide-only group had significantly poorer beta-cell function than both the combination treatment group and the placebo group.
Combination therapy resulted in the lowest on-treatment glucose levels, although this was not statistically significant, and a significant 32% reduction in insulin dose relative to placebo.
Pieber noted that there was “no safety concern whatsoever” for any of the treatments, with adverse events occurring at a similar rate across all four groups.
The CXCR1/2 inhibitor ladarixin, which blocks the activity of IL-8, was also tested in a phase 2 trial, but involving only 76 participants, all with new-onset type 1 diabetes.
The trial missed its primary endpoint of slowing the decline of beta-cell function during 3 months of treatment. However, among participants with severe-onset disease (baseline C-peptide below the trial population median), C-peptide was nonsignificantly higher in the ladarixin than placebo group at 3 months, and this reached statistical significance at 6 months (3 months after treatment ended), although the difference disappeared by month 12. Likewise, people in this subgroup taking ladarixin had lower glycated hemoglobin levels than those taking placebo.
Presenter Paolo Pozzilli (University of Rome, Italy) therefore concluded that further investigation of ladarixin is worthwhile, and revealed that a phase 3 trial is due to begin soon.
Another phase 2 trial – the T1GER study, presented as a late-breaking poster – produced positive results for golimumab in people with newly diagnosed type 1 diabetes.
The 56 children and young adults (average age 14 years) randomly assigned to receive the medication had a significantly slower reduction in beta-cell function over 52 weeks of treatment compared with the 28 who were given placebo. At week 52, the average 4-hour C-peptide AUC was 0.64 versus 0.43 pmol/mL. Also, insulin needs increased by a corresponding least squares mean of 0.07 and 0.24 U/kg per day, which was a significant difference favoring golimumab.
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ADA Scientific Sessions; 12–16 June 2020 (278-OR)
ADA Scientific Sessions; 12–16 June 2020 (249-OR)
ADA Scientific Sessions; 12–16 June 2020 (3-LB)