Emerging Anti-Diabetic Drugs for Beta-Cell Protection in Type 1 Diabetes

Abstract

Type 1 diabetes (T1D) is a chronic autoimmune disorder that damages beta cells in the pancreatic islets of Langerhans and results in hyperglycemia due to the loss of insulin. Exogenous insulin therapy can save lives but does not halt disease progression. Thus, an effective therapy may require beta-cell restoration and suppression of the autoimmune response. However, currently, there are no treatment options available that can halt T1D. Within the National Clinical Trial (NCT) database, a vast majority of over 3000 trials to treat T1D are devoted to insulin therapy. This review focuses on non-insulin pharmacological therapies. Many investigational new drugs fall under the category of immunomodulators, such as the recently FDA-approved CD-3 monoclonal antibody teplizumab. Four intriguing candidate drugs fall outside the category of immunomodulators, which are the focus of this review. Specifically, we discuss several non-immunomodulators that may have more direct action on beta cells, such as verapamil (a voltage-dependent calcium channel blocker), gamma aminobutyric acid (GABA, a major neurotransmitter with effects on beta cells), tauroursodeoxycholic acid (TUDCA, an endoplasmic reticulum chaperone), and volagidemab (a glucagon receptor antagonist). These emerging anti-diabetic drugs are expected to provide promising results in both beta-cell restoration and in suppressing cytokine-derived inflammation.

Tauroursodeoxycholic acid: a bile acid that may be used for the prevention and treatment of Alzheimer’s disease

“…By manipulating GLP-1 activity, the aggregation of amyloid-β in AD can be regulated, and GLP-1 receptor agonists could alleviate hippocampal neurodegeneration ( Batista et al, 2019 ). To sum up, based on the evidence that TUDCA has become an emerging anti-diabetic drug ( Ajmal et al, 2023 ), investigating how TUDCA can impact AD by improving metabolism could potentially extend the therapeutic benefits of TUDCA beyond just AD.…”