Do glucagon-like peptide-1 receptor (GLP-1R) agonists have potential as adjuncts in the treatment of type 1 diabetes?

ABSTRACT

Introduction: Glucagon-like peptide-1 (GLP-1) is produced by the gut, stimulates insulin secretion from the pancreatic β-cells, and inhibits glucagon secretion from the α-cells. The GLP-1 receptor (GLP-1R) agonists are used in the treatment of type 2 diabetes (T2DM).

Area covered: This review covers the clinical trials of the GLP-1R agonists (exenatide and liraglutide) and their potential as adjunct treatment in type 1 diabetes mellitus (T1DM).

Expert opinion: GLP-1R agonists are unable to increase insulin secretion, in subjects with T1DM, who are C-peptide negative. Also, the GLP-1R agonists either have no effect or cause a small inhibition of glucagon secretion in subjects with T1DM. There is no evidence that the GLP-1R agonists cause a major reduction in HbA1c, or have a major effect on hypo- or hyperglycemia in subjects with TD1M. The main beneficial effect of the GLP-1R agonists is probably the modest weight loss, which may underlie the reduction in dose of insulin used. Given that the GLP-1R agonists cause gastrointestinal adverse effects, and with reduced insulin doses, increase the risk of ketosis, it seems to me that the risk with these agents may outweigh any benefit in T1DM, and that they have little potential as adjuncts in the treatment of T1DM.

KEYWORDS:

• Clinical trials
• exenatide
• glucagon
• glucagon-like peptide 1
• glycemic control
• insulin dose
• liraglutide
• type 1 diabetes mellitus

Article highlights

• The GLP-1R agonists are unable to increase insulin secretion, in subjects with T1DM, who are C-peptide negative.

• The GLP-1R agonists either have no effect or cause a small inhibition of glucagon secretion in subjects with T1DM.

• The GLP-1R agonists do not cause a major reduction in HbA1c, or have a major effect on hypo- or hyperglycemia in subjects with T1DM.

• The main beneficial effect of the GLP-1R agonists in subjects with T1DM is probably the modest weight loss, but the GLP-1R agonists also cause gastrointestinal adverse effects and may increase the risk of ketosis with reduced insulin dosing

• The GLP-1R agonists have little potential as adjuncts in the treatment of T1DM.

This box summarizes key points contained in the article.

Declaration of interest

S Doggrell has 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 manuscript was not funded.