New metric shows diabetes drug works

In type 1 diabetes (T1D), immune cells gradually attack and kill off the pancreas’s insulin-producing ß-cells. Therapies to moderate this autoimmune destruction in recent-onset T1D have shown success, but scientists haven’t known whether these therapies were preventing ß-cell killing, or merely restoring some ß-cell function.

When ß-cells die, they release modified versions of the insulin DNA (INS DNA) into the blood. Knowing this, Yale researchers recently devised a new method for measuring ß-cell death in vivo: directly measuring the modified INS DNA in the blood serum. The researchers successfully used this method to study diabetic mice, and more recently measured INS DNA in human patients with T1D in a phase 2 clinical trial of the monoclonal antibody drug teplizumab.

Teplizumab, when given in two courses one year apart, significantly reduced ß-cell loss in patients with early-onset T1D, the team reported in the May issue of Diabetes. The level of ß-cells at year two was, on average, 75 percent higher in the teplizumab arm of the trial than in the control group.

If approved by the FDA, teplizumab would be “the first drug to change the natural course of T1D since insulin,” says Kevan Herold, M.D., professor of immunobiology and medicine and lead author of the study.