Treatment Delays Onset of Diabetes in At-Risk Populations

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A single course of treatment with teplizumab delayed the development of type 1 diabetes in at-risk teens and children, shows a study presented at the American Diabetes Association annual meeting earlier this month.

A single course of treatment with teplizumab delayed the development of type 1 diabetes in at-risk teens and children, shows a study presented at the American Diabetes Association annual meeting earlier this month.

The study, by Kevan Herold, M.D., of Yale University, was a phase two randomized, placebo-controlled, double-blind trial of teplizumab, a novel monoclonal antibody. It included 76 patients (mean age 18 years) who had a relative with diabetes, but hadn’t developed the condition. The study participants had at least two autoantibodies and abnormal results of an oral glucose-tolerance test at baseline. They were assigned to a single 14-day course of teplizumab or placebo with follow-up testing every six months.

Less than half of the participants who received teplizumab (43 percent) were diagnosed after 48 months, while 72 percent of those who received placebo developed diabetes on an average of two years. This translated into annual rates of diagnosis of type 1 diabetes of 14.9 percent per year for teplizumab compared to 35.9 percent for those taking the placebo.

“The people who enrolled in the study didn’t have diabetes and don’t see physicians for care of diabetes. They don’t take insulin, don’t follow a diet or do any of the other things that people with diabetes need to do,” Dr. Herold said. “I am hoping this result will generate discussion about how to implement this preventative approach. Now that we have a treatment for delay and possibly prevention should we screen a larger group (those in the trial were relatives), even the general population.”

The treatment effect was greatest after the first year. During year one, diabetes was diagnosed in only three of 44 participants (7 percent) in the teplizumab group, but in 14 of 32 participants (44 percent) in the placebo group. The treatment effect diminished overall after three years.

“We can’t really say that the treatment effect wanes after two or three or even more years in a given individual,” Dr. Herold said. “We can say that as a group there is waning of the effect but in our previous trial (AbATE) there was a group that showed very robust responses and a group that did not. It could be that those who have not developed diabetes by three years will continue to be diabetes free or they could lose any clinical benefit. We certainly need to follow the participants to figure this out.”

Currently, an estimated 1.5 million young adults in the U.S. have been diagnosed with type 1 diabetes. Immune therapies that target preservation of beta function have shown the most promise in patients with recent-onset clinical type 1 diabetes. By modifying the function of CD-8 and T lymphocytes that promote the destruction of beta cells, teplizumab has been shown to reduce the loss of beta cell function for long as seven years following diagnosis of type 1 diabetes.

“Our data suggest that responses to teplizumab differ on the basis of characteristics of the participants. The absence of one type 1 diabetes–associated MHC allele, HLA-DR3, but the presence of HLA-DR4, as well as the absence of anti-ZnT8 antibodies identified the persons most likely to have a response,” Dr. Herold said. Larger studies are warranted, he said.

REFERENCES

Herold KC, Bundy BN, Long SA, et al. “An Anti-CD3 Antibody, Teplizumab, in Relatives at Risk for Type 1 Diabetes.” New England Journal of Medicine. 2019 Jun 9. doi: 10.1056/NEJMoa1902226.

Perdigoto AL, Preston-Hurlburt P, Clark P, Long SA, et al. “Treatment of type 1 diabetes with teplizumab: clinical and immunological follow-up after 7 years from diagnosis.” Diabetologia. 2019;62:655-664. doi: 10.1007/s00125-018-4786-9.