A world-first clinical trial has found that baricitinib, a drug commonly prescribed for rheumatoid arthritis, preserved the pancreatic cells’ ability to produce their own insulin and slowed the progression of type 1 diabetes in those recently diagnosed with the condition. The drug shows promise as the first disease-modifying treatment for type 1 diabetes that can be given as a tablet.
Type 1 diabetes occurs when the body’s immune system attacks and destroys the pancreas’ insulin-secreting cells. However, because the destruction is progressive, there are still a substantial number of cells capable of producing insulin early on in the disease.
A world-first clinical trial, led by researchers from the St Vincent’s Institute of Medical Research (SVI) in Melbourne, has shown that an existing drug, commonly prescribed for rheumatoid arthritis, given to newly diagnosed type 1 diabetics protects these still-functional cells, preserving the body’s own insulin production and slowing the progression of the disease.
“When type 1 diabetes is first diagnosed, there is a substantial number of insulin-producing cells still present,” said Tom Kay, one of the study’s co-authors. “We wanted to see whether we could protect further destruction of these cells by the immune system. We showed that baricitinib is safe and effective at slowing the progression of type 1 diabetes in people who have been recently diagnosed.”
In the phase 2 trial, the researchers randomly assigned 91 patients aged 10 to 30 diagnosed with type 1 diabetes during the previous 100 days to receive 4 mg/day of baricitinib or a placebo for 48 weeks. Baricitinib blocks the actions of Janus kinase (JAK) enzymes, which control inflammation. It’s approved as a treatment for the autoimmune diseases rheumatoid arthritis and alopecia areata.
The trial primarily investigated the drug's effect on the level of C-peptide, the gold-standard measure of endogenous insulin secretion in type 1 diabetics, but also investigated participants’ daily need for injected insulin, HbA1c, a marker of long-term blood sugar control, and their blood glucose variability within a day, measured using continuous glucose monitoring (CGM). Within-day glucose variability, called the coefficient of variation (CV), is represented as a percentage, with ‘stable’ glucose levels defined as those less than 36% and ‘unstable’ levels 36% and above.
The researchers found that, at 48 weeks, the baricitinib group had higher mean C-peptide levels compared to controls (0.65 nmol/L/min vs 0.43 nmol/L/min), indicating that the pancreatic cells were being preserved and were able to produce their own insulin. In the treatment group, the mean daily insulin dose at 48 weeks was 0.41 units/kg/day and 0.52 units/kg/day in the control group. Although HbA1c levels were similar between the two groups, the CV at 48 weeks in the baricitinib group was 29.6% compared to 33.8% in the placebo group. No serious adverse events were attributed to the drug.
“Up until now, people with type 1 diabetes have been reliant on insulin delivered via injection or infusion pump,” Kay said. “Our trial showed that, if started early enough after diagnosis, and while the participants remained on the medication, their production of insulin was maintained. People with type 1 diabetes in the trial who were given the drug required significantly less insulin for treatment.”
The researchers are hopeful that baricitinib will become clinically available as a way of better managing type 1 diabetes to avoid the long-term complications associated with poor blood sugar control, such as heart attack and stroke, vision impairment, kidney disease and nerve damage.
“We are very optimistic that this treatment will become clinically available,” said Helen Thomas, study co-author. “This would be a huge step-change in how type 1 diabetes is managed, and we believe it shows promise as a fundamental improvement in the ability to control type 1 diabetes.”
The study was published in The New England Journal of Medicine, and the below videos, produced by SVI, explain the research and the clinical trial’s findings.
Source: SVI
