Cancer Drug May Slow Course of Type 1 Diabetes
NEW YORK (Reuters Health) – The tyrosine-kinase inhibitor imatinib used to treat chronic myeloid leukemia and other cancers may help preserve beta-cell function in people with recently diagnosed type-1 diabetes, according to findings from a phase-2 study.
Type-1 diabetes stems from autoimmune-mediated destruction of insulin-producing beta cells in the pancreas. Imatinib may affect relevant immunological and metabolic pathways and has been shown to prevent diabetes and induce remission of recent-onset diabetes in preclinical studies.
Dr. Stephen Gitelman of the University of California, San Francisco, and colleagues evaluated the safety and efficacy of imatinib in preserving beta-cell function in 67 adults with recent-onset type-1 diabetes. The participants were randomly allocated to 400 mg/day imatinib or placebo for 26 weeks.
The primary outcome was the difference between groups in C-peptide area under the curve (AUC) over the first two hours of a mixed-meal glucose-tolerance test (MMGT), a measure of endogenous insulin production.
After withdrawals, 43 participants in the imatinib group and 21 in the placebo group were included in the primary intention-to-treat (ITT) analysis at 12 months.
The imatinib group achieved the primary endpoint, showing an increase in C-peptide AUC in response to the MMGT at 12 months, the researchers report in The Lancet Diabetes and Endocrinology.
The adjusted mean difference in two-hour C-peptide AUC at 12 months for imatinib versus placebo treatment was 0.095 (90% confidence interval, -0.003 to 0.191; P=0.048, one-tailed test) and constituted a 19.4% treatment effect (difference in the adjusted 12-month means divided by the placebo group mean).
However, this effect was not sustained during a second year of observation off imatinib.
Secondary and exploratory analyses did not show clear effects of imatinib on immune responses, but did show a series of unique effects on metabolism, with improved beta-cell function and insulin sensitivity.
The most common side effects with imatinib included gastrointestinal issues (primarily self-limited and transient nausea) and additional laboratory issues (associated with changes in liver function tests and abnormal complete blood cell counts).
“In general, imatinib was well tolerated, and if participants did develop adverse events, they tended to occur early in the course of drug administration, to be milder than that described in the oncology literature, and usually resolved in the ensuing days and weeks with ongoing therapy,” the researchers report.
“These initial observations suggest considerations for future study of imatinib in type 1 diabetes, provided treated participants are closely monitored for possible toxicities,” they conclude.
“This study is the first to use a tyrosine kinase inhibitor in human type 1 diabetes,” Dr. Jay Skyler of the Diabetes Research Institute at the University of Miami writes in a linked Comment.
The data on the mechanistic effects of imatinib on metabolic function “add to our understanding of how the intervention works” and suggests that “we should not anticipate that effects on beta-cell health or function will persist after discontinuation of the intervention,” he adds.
“In other immune-mediated diseases, such as rheumatoid arthritis or psoriasis, disease-modifying therapies are continued indefinitely. Given the decrease in beta-cell function after discontinuation of the intervention in the current study and other recent studies in type 1 diabetes, investigating the effect of continued disease-modifying drug intervention in type 1 diabetes seems prudent,” Dr. Skyler concludes.
The study was funded by the Juvenile Research Diabetes Foundation.
SOURCE: https://bit.ly/3jNvcTz and https://bit.ly/3jPOUOO Lancet Diabetes and Endocrinology, online June 29, 2021.
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