New and emerging therapies in type 1 diabetes mellitus
Kevan C. Herold, Carmella Evans-Molina
Kevan C. Herold, Carmella Evans-Molina
View: Text | PDF
Review

New and emerging therapies in type 1 diabetes mellitus

Abstract

Type 1 diabetes mellitus (T1D) has been recognized as a chronic autoimmune disease for five decades, but therapy has relied on the exogenous replacement of insulin, which is an imperfect substitute for normal β cell function. In recent years, there has been progress in the development of new therapeutics that target the primary causes of the disease: failed immunologic tolerance and β cell killing. One agent, teplizumab, was shown to attenuate loss of β cell function that occurs over time and delay progression to clinical disease in individuals at risk, leading to its regulatory approval in 2022. Other immunologic agents show promise in modulating the immunologic imbalance. Moreover, a role for β cells in T1D pathogenesis has been identified and may be targeted. Now that the first disease-modifying therapeutic agent is available, future studies may involve combinations of agents to extend immunologic tolerance and protect and restore β cells so that lasting metabolic remission can be achieved.

Authors

Kevan C. Herold, Carmella Evans-Molina

×

Figure 1

Progression of β cell loss in T1D.

Options: View larger image (or click on image) Download as PowerPoint
Progression of β cell loss in T1D. The progression from the first discov...
The progression from the first discovery of autoantibodies to clinical disease has been described in stages that are defined by metabolic criteria, but these measures are not fixed, and the kinetics of progression are variable among individuals. Even five years before clinical diagnosis, or at the time of stage 1 T1D, β cell function is reduced in response to an oral glucose tolerance test compared with autoantibody-negative individuals without T1D. β Cell function, as assessed by C-peptide responses to an oral glucose tolerance test, shows the greatest decline just prior to the onset of clinical hyperglycemia (stage 3 T1D) (148, 149). Among individuals diagnosed with stage 2 T1D, the median time to stage 3 T1D is approximately two years (119). Notably, younger individuals typically progress more rapidly than do older individuals through early stages to clinical T1D and lose C-peptide more rapidly after stage 3 onset.