Type 1 diabetes: key drug targets and how they could influence future therapeutics

ABSTRACT

Introduction

Despite significant strides made in the management of T1DM, standard management is still insulin analog therapy. Some non-insulin therapies traditionally reserved for the treatment of T2DM have been explored in caring for patients with T1DM, and pancreas transplant is an option for few. However, T1DM remains a challenging disease to manage, encouraging development of novel pharmacologic agents.

Areas covered

We retrieved PubMed, Cochrane Library, Scopus, Google Scholar, and ClinicalTrials.gov records to identify studies and articles focused on new pharmacologic advances to treat T1DM.

Expert opinion

Recent research has focused on new targets of pharmacologic treatment of T1DM. Beta-cell preservation through immunomodulation or inhibiting inflammation hopes to delay or halt the progression of the disease. Beta cell regeneration through islet cell transplant or modification in transcription pathways aim to reverse the disease effects. Multiple other new targets such as glucagon antagonism and glucokinase activation are also in development as a potential adjunctive therapy. These new therapeutic targets offer the hope of reducing the daily burden of diabetes management with eventual insulin discontinuation for many individuals with T1DM.

KEYWORDS:

• Beta cell destruction
• beta cell regeneration
• glucagon antagonist
• glucokinase activator
• inceptor
• type 1 diabetes

Article highlights

• Disease burden of T1DM remains significant despite the advancements in insulin delivery systems.

• There is still an unmet need to treat T1DM in ways that do not expose patients to great risks of hypoglycemia.

• The autoimmune nature of T1DM may allow for new therapy targets to reverse or arrest the disease progression, or regenerate the destroyed islet cells via endogenous or exogenous pathways.

• One of the biggest challenges in many of these new targets remain achieving disease-specific immune suppression, with minimal adverse effects.

• While many of the discussed targets are still in early stages of research, some have already shown positive data in delaying clinically significant T1DM or helping alleviate the disease burden as adjunctive therapies.

This box summarizes key points contained in the article.

Abbreviations

CAR, chimeric antigen receptor; FDA, Food and Drug Administration; GABA - γ-aminobutyric acid; Tregs, regulatory T cells; GAD, glutamic acid decarboxylase; LADA, latent autoimmune diabetes of adulthood; T1DM, type 1 diabetes mellitus; TNF- α, Tumor necrosis factor-α

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.