A great prospect for type 1 diabetes

Type 1 diabetes is a devastating life-long condition. It is autoimmune and frequently occurs in predisposed young adults. Chronic therapy is insulin use via multiple daily injections or insulin-pump; in addition to intensive lifestyle modifications.

The best management of type 1 diabetes is proactive prevention or elimination rather than reactive insulin usage. The current study addresses this very point. A group of 76 participants at high-risk for DM1 was randomized to receive teplizumab or placebo. The presence of autoantibodies to various entities such as GAD65, MicroIns, IA2, ICA, and ZnT8 defined the high-risk status.

Investigators followed subjects for six years. Remarkably at any point in time; teplizumab prevented the development of type 1 diabetes by about 60%. The annual rate of diagnosed diabetes was 16% vs. 39% in those treated with and without teplizumab.

Teplizumab is an immune modulator via CD3 co-receptor pathway. Treated patients experienced a higher rate of adverse events in the form of rash and temporary reduction in lymphocyte count.

I anticipate that further intense research on the subject will yield even higher rates of prevention in predisposed individuals. Family history and biochemical screening of patients would be parament. Stay tuned for similar research results as the DM1-prevention space is blossoming.

GT

Also see:

Diabetes Type 1

Diabetes prevention

ADA


N E J M

Phase 2 RCT

August 2019

BACKGROUND

Type 1 diabetes is a chronic autoimmune disease that leads to destruction of insulin-producing beta cells and dependence on exogenous insulin for survival. Some interventions have delayed the loss of insulin production in patients with type 1 diabetes, but interventions that might affect clinical progression before diagnosis are needed.

METHODS

We conducted a phase 2, randomized, placebo-controlled, double-blind trial of teplizumab (an Fc receptor–nonbinding anti-CD3 monoclonal antibody) involving relatives of patients with type 1 diabetes who did not have diabetes but were at high risk for development of clinical disease.

Patients were randomly assigned to a single 14-day course of teplizumab or placebo, and follow-up for progression to clinical type 1 diabetes was performed with the use of oral glucose-tolerance tests at 6-month intervals.

RESULTS

A total of 76 participants (72% were ≤18 years of age) underwent randomization — 44 to the teplizumab group and 32 to the placebo group.

The median time to the diagnosis of type 1 diabetes was 48.4 months in the teplizumab group and 24.4 months in the placebo group; the disease was diagnosed in 43% of the participants who received teplizumab and in 72% of those who received placebo.

HR for the diagnosis of type 1 diabetes (teplizumab vs. placebo) was 0.41 (p=0.006 by adjusted Cox proportional-hazards model).

The annualized rates of diagnosis of diabetes were 14.9% per year in the teplizumab group and 35.9% per year in the placebo group.

There were expected adverse events of rash and transient lymphopenia. KLRG1+TIGIT+CD8+ T cells were more common in the teplizumab group than in the placebo group.

Among the participants who were HLA-DR3 (-), HLA-DR4 (+), or anti–zinc transporter 8 antibody (-), fewer participants in the teplizumab group than in the placebo group had diabetes diagnosed.

CONCLUSIONS

Teplizumab delayed progression to clinical type 1 diabetes in high-risk participants.