A drug called golimumab currently on the market for other autoimmune conditions can help kids and young adults newly diagnosed with Type 1 diabetes still produce insulin, according to new research.
The drug can preserve the beta cells of children and young adults newly diagnosed with Type 1 diabetes for at least a year after diagnosis, the study shows.
The findings represent a major step forward in the effort to find ways to preserve the insulin-making capabilities of children and young adults with Type 1 diabetes.
The new study in the New England Journal of Medicine reports on the 52-week treatment period. Researchers will follow with a period where they monitor participants when they don’t take the drug.
“The main goal of the study was to see if golimumab could preserve beta-cell function in these newly diagnosed patients, and it does.”
The Phase 2 study demonstrates that golimumab, an anti-tumor necrosis factor (TNF) therapy, reduced the amount of injected insulin children and young adults with newly diagnosed Type 1 diabetes need to take by preserving their ability to produce insulin on their own, called endogenous insulin.
The need for less injected insulin is a major quality of life improvement for patients with Type 1 diabetes, according to the researchers.
Golimumab, marketed as Simponi, is currently approved to treat rheumatoid arthritis, ulcerative colitis, and other autoimmune conditions, but the US Food and Drug Administration has not approved it for the treatment of Type 1 diabetes.
Golimumab and beta-cell function
“The most important finding of our work is that this drug, golimumab, is a potential disease-modifying agent for newly diagnosed Type 1 diabetes,” says first author Teresa Quattrin, professor of pediatrics at the University at Buffalo. “The main goal of the study was to see if golimumab could preserve beta-cell function in these newly diagnosed patients, and it does.”
The team determined that beta-cell function was preserved based on the amount of C-peptide in patients’ blood during a four-hour mixed meal tolerance test. Because C-peptide reflects only insulin made by the body and not injected insulin, C-peptide levels reveal how well the pancreas is producing insulin.
Patients treated with golimumab had higher C-peptide levels at week 52 compared to placebo. “This was statistically significant, thus the study met its primary goal,” Quattrin says. “In fact, 41% of participants receiving golimumab had an increase or less than 5% decrease in C-peptide compared to only 11% in the placebo group.”
Type 1 diabetes ‘honeymoon period’
The current study is the culmination of decades of work that Quattrin has conducted at the University at Buffalo and at the Diabetes Center at UBMD Pediatrics and John R. Oishei Children’s Hospital. She has been interested in finding ways to extend the remission, or honeymoon period, to preserve the ability of recently diagnosed Type 1 diabetes patients to continue to make insulin on their own.
“Patients newly diagnosed with Type 1 diabetes don’t stop making insulin all of a sudden.”
Patients newly diagnosed with Type 1 diabetes generally have elevated levels of tumor necrosis factor alpha, which is directly toxic to the pancreatic beta cells that produce insulin. In 2009, building on positive findings in animal models treated with anti-TNF therapy, Quattrin and her team published a randomized pilot study where 10 patients received another TNF inhibitor and eight received placebo starting within 28 days from diagnosis. The results of that small proof-of-concept study strongly suggested that this class of drugs might be able to preserve beta-cell function in newly diagnosed patients with Type 1 diabetes.
“Patients newly diagnosed with Type 1 diabetes don’t stop making insulin all of a sudden,” explains Quattrin. “During the period just after diagnosis, called partial remission or the honeymoon period, patients are still able to make some insulin on their own. That is the period we have targeted with this study of golimumab.”
Nearly 43% of those in the current study who received golimumab were in partial diabetes remission versus 7% of those receiving placebo. The definition of partial remission was based on insulin dose and blood sugar control levels as indicated by hemoglobin A1C, a measurement of average blood sugar levels over three months.
Better blood sugar control
While both groups of patients in the current study achieved good blood sugar control, those receiving golimumab did so with less injected insulin, which Quattrin described as a critical benefit.
“During the 52 weeks of the study, insulin dose increased only slightly for those on golimumab, 0.07 units per kilogram (about 2.2 pounds) per day, versus 0.24 units per kilogram per day for those on placebo. Moreover, in a post-hoc analysis, an analysis conducted after the conclusion of the clinical trial, those who were younger than 18 years had 36% fewer episodes where blood sugar was less than 54 mg per deciliter, designated by the American Diabetes Association as level 2 hypoglycemia,” Quattrin says.
This is important clinically because low blood sugar reactions are dangerous and can prove fatal if untreated. Episodes of low blood sugar require immediate attention, often causing disruption to the child (e.g., they have to be removed from class or recreation/sports activities), thereby compromising quality of life.
A child with Type 1 diabetes requires about 1 unit of insulin per kilogram of body weight per day, Quattrin says. That means that a child weighing about 65 pounds typically requires about 30 units of injected insulin per day once they are out of the partial remission period, about three to six months after diagnosis.
Parents or the participants themselves administered Golimumab as a subcutaneous injection every two weeks. No serious side effects related to the study drug, such as serious infections, were reported.
Researchers conducted the randomized, controlled clinical trial at 27 centers throughout the US, including at the Diabetes Center at UBMD Pediatrics and Oishei Children’s Hospital in Buffalo. It involved 84 patients, aged 6 to 21 years, with two-thirds receiving golimumab and one-third receiving placebo starting within 100 days from diagnosis.
Additional coauthors are from the University of Florida, the University of Colorado, Emory University, and Janssen Research & Development LLC. The World Without Disease Accelerator, a group within Janssen Research & Development LLC, funded the study.
Source: University at Buffalo
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