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US approves new drug to delay onset of diabetes in children

A new kind of therapy that could delay the start of type 1 diabetes in children by up to three years – thought to be the first to postpone the start of any autoimmune condition – has been approved for use in America, after years of development.

The treatment, called teplizumab, works by partially blocking the immune system’s attack on insulin-making cells in the pancreas, reports New Scientist.

Delaying the onset of type 1 diabetes should make it easier for children to cope with the condition and reduce its toll on their health, says Kevan Herold at Yale University, who was involved in the drug’s development.

Type 1 diabetes tends to start in children and young adults. Those affected must inject insulin with their meals to prevent their blood sugar levels rising too high. They must also frequently measure their blood sugar levels and control what they eat.

“This is a 24/7 disease – you don’t go to sleep, you don’t eat, without consideration of the disease. Any time without it is of value,” says Herold.

The immune attack happens over several years and involves many aspects of the immune system. If a child is suspected to be at risk, they can be monitored with blood tests for antibodies that damage pancreas cells.

Teplizumab, made by New Jersey-based firm Proventionbio, has been approved for people aged eight and over who have these antibodies but don’t yet have blood sugar levels so high that they are classed as having diabetes.

The drug is thought to work by lowering the activity of a subset of immune cells called T-cells, which are involved in killing the insulin-making pancreas cells. It is given by daily infusions in hospital for two weeks.

An ongoing 76-person trial was the basis for the US approval. In the trial, teplizumab is given to people aged between eight and 49 who don’t have type 1 diabetes, but have a relative with the condition. Among the participants who have developed type 1 diabetes so far, teplizumab delayed the condition’s onset by nearly three years, compared with those receiving placebo infusions.

Teplizumab has caused a higher rate of side effects, such as a rash, than the placebo infusions. Despite teplizumab targeting some immune cells, the number of everyday infections is similar between the two groups.

In separate trials, the drug was given to several hundred people with newly diagnosed type 1 diabetes to determine whether it reduces the condition’s severity. So far, the US Food and Drug Administration (FDA) has only approved teplizumab for delaying type 1 diabetes among people who do not yet have the condition.

The new approach opens the possibility that type 1 diabetes could be delayed further by adding in other drugs that affect the immune system, says Herold. “No one is saying this is the final word. Maybe we could give this drug followed by something else.”

The trials recruited children and young adults who had a close relative with the condition, as well as the tell-tale antibodies. This approach wouldn’t pick up everyone who develops type 1 diabetes because many of those affected don’t have a close relative with the condition.

Other screening methods are being investigated, including genetic tests. Those found to be at higher risk would still need periodic tests to see if the immune attack had started.

“If you use multiple genes, you are going to capture a lot more children and adults who are at risk of developing type 1 diabetes,” says Rachel Besser at the University of Oxford.

Screening programmes mean children can be diagnosed and start insulin injections earlier. “There’s a great advantage in being able to identify children early,” says Besser. “It prevents hospitalisations, which carry with them trauma and distress.”

Teplizumab is under review by drug regulators in the UK and continental Europe under fast-track pathways designed for particularly innovative new medicines.

Study details

Teplizumab improves and stabilizes beta cell function in antibody-positive high-risk individuals

Emily Sims, Brian Bundy, Kenneth Stier, Elisavet Serti and type 1 diabetes Trialnet Study Group et al.

Published in Science Translational Medicine on 3 March 2021


We analysed the effects of a single 14-day course of teplizumab treatment on metabolic function and immune cells among participants in a previously reported randomised controlled trial of nondiabetic relatives at high risk for type 1 diabetes (T1D). In an extended follow-up (923-day median) of a previous report of teplizumab treatment, we found that the median times to diagnosis were 59.6 and 27.1 months for teplizumab- and placebo-treated participants, respectively (HR = 0.457, P = 0.01). Fifty percent of teplizumab-treated but only 22% of the placebo-treated remained diabetes-free. Glucose tolerance, C-peptide area under the curve (AUC), and insulin secretory rates were calculated, and relationships to T cell subsets and function were analysed. Teplizumab treatment improved beta cell function, reflected by average on-study C-peptide AUC (1.94 versus 1.72 pmol/ml; P = 0.006). Drug treatment reversed a decline in insulin secretion before enrolment, followed by stabilization of the declining C-peptide AUC seen with placebo treatment. Proinsulin:C-peptide ratios after drug treatment were similar between the treatment groups. The changes in C-peptide with teplizumab treatment were associated with increases in partially exhausted memory KLRG1+TIGIT+CD8+ T cells (r = 0.44, P = 0.014) that showed reduced secretion of IFNγ and TNFα. A single course of teplizumab had lasting effects on delay of T1D diagnosis and improved beta cell function in high-risk individuals. Changes in CD8+ T cell subsets indicated that partially exhausted effector cells were associated with clinical response. Thus, this trial showed improvement in metabolic responses and delay of diabetes with immune therapy.


Science Translational Medicine article – Teplizumab improves and stabilizes beta cell function in antibody-positive high-risk individuals (Open access)


New Scientist article – Drug that delays onset of type 1 diabetes gets approval in US (Open access)


See more from MedicalBrief archives:


In milestone trial, experimental drug markedly delays type 1 diabetes


Rotavirus vaccine also protects children against type 1 diabetes


Worldwide type 1 diabetes cases expected to double by 2040 – Australian study


Verapamil benefits for Type 1 diabetes evident two years later – University of Alabama




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