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07-07-2021 | Immunotherapy | News

Imatinib could slow beta-cell decline in early type 1 diabetes

Author: Laura Cowen

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medwireNews: A 6-month course of treatment with the tyrosine kinase inhibitor imatinib may slow the decline in beta-cell function in people with newly diagnosed type 1 diabetes, but the effect is not sustained in the longer term, phase 2 study findings indicate.

“Imatinib might offer unique benefits to patients with type 1 diabetes and provide a novel means to target β-cell health and insulin sensitivity,” Stephen Gitelman (University of California San Francisco, USA) and co-authors write in The Lancet Diabetes & Endocrinology.

However, they caution that “treated participants should be monitored closely for potential side-effects and toxicities that require modification to imatinib dosing.”

The multicenter study randomly assigned people with recent-onset type 1 diabetes (<100 days from diagnosis) to receive four 100 mg imatinib mesylate tablets per day (n=45) or matched placebo (n=22) for 6 months.

At 12 months, the mean area under the curve for 2-hour C-peptide response to a 4-hour mixed meal tolerance test was higher in the imatinib group than in the placebo group, at 0.583 versus 0.489 nmol/L.

After adjustment for sex, and baseline age and C-peptide levels, the mean difference between the two groups was 0.095 nmol/L, which was equivalent to a treatment effect of 19.5%, the researchers remark.

But at the 18- and 24-month assessments, the difference between the two groups was minimal.

Commenting on the findings, Jay Skyler, from the University of Miami in Florida, USA, said that the results of this and other studies “indicate the fallacy of stopping treatment after the initial intervention period and expecting some retention of treatment effects after discontinuation.”

He added: “Given the decrease in β-cell function after discontinuation of the intervention […] investigating the effect of continued disease-modifying drug intervention in type 1 diabetes seems prudent.”

In secondary analyses, glycated hemoglobin levels were lower in the imatinib group than in the placebo group during the active treatment phase. And in further exploratory analyses, beta-cell glucose sensitivity increased to higher than baseline level at 3 months in the imatinib group, then stabilized up to 6 months, but decreased thereafter. By contrast, this measure gradually decreased with time in the placebo group.

In addition, insulin secretion rates, calculated at matched glycemia levels (7 mmol/L) were higher with imatinib than placebo at 6 months, while insulin sensitivity remained stable during imatinib treatment, but declined with placebo.

Gitelman et al say that these findings “support an improvement in β-cell function” during imatinib treatment.

They also note that the drug was “well tolerated, and if participants did develop adverse events, they tended to occur early in the course of drug administration […] and usually resolved in the ensuing days and weeks with ongoing therapy.”

Temporary dose modifications due to adverse events were needed in 38% of participants in the imatinib arm, with 13% needing to discontinue treatment permanently. In the placebo arm 23% of participants required dose modifications and none discontinued treatment.

Gitelman and co-authors say that future studies “could explore lower doses and longer durations of [imatinib]; extend related studies to children and adolescents; assess imatinib in a population at risk of type 1 diabetes to delay or prevent progression to disease; and assess imatinib in combination with drugs that work by [complementary] mechanisms, such as one of the previously successful and more traditional immunotherapies.”

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)00139-X
Lancet Diabetes Endocrinol 2021; doi:10.1016/S2213-8587(21)00169-8

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