Emerging glucagon-like peptide 1 receptor agonists for the treatment of obesity

ABSTRACT

Introduction: Obesity is a growing threat to public health, increasing risks of numerous diseases and mortality, and impairing quality of life. If current trends continue, more than 1.1 billion individuals will have obesity in 2030, corresponding to almost 2.5 times the number of adults currently living with diabetes. There is a strong interest in developing obesity treatments based on glucagon-like peptide-1 (GLP-1) agonism, which have proved to limit morbidity and mortality in type 2 diabetes.

Areas covered: This review provides an overview of current compounds containing GLP-1 receptor agonism in clinical development for obesity, with mono-activity at the GLP-1 receptor (PF-0688296, glutazumab, semaglutide) or engaging one or more other endogenous hormonal systems involved in energy balance and metabolism, including glucagon, oxyntomodulin, glucose-dependent inhibitory peptide and amylin (CT-868, CT-388, AMG 133, tirzepatide, NNC9204-1177, JNJ-54,728,518, SAR425899, pegapamodutide, MK8521, cotadutide, efinopegdutide, BI-456,906, cagrilintide + semaglutide 2,4 mg, HM15211, NNC9204-1706).

Expert opinion: Many novel compounds employing GLP-1 receptor agonism are in clinical development. Semaglutide is farthest in clinical development and will presumably become a benchmark for this class of novel anti-obesity compounds.

KEYWORDS:

• GLP-1
• semaglutide
• tirzepatide
• obesity
• glutazumab
• cagrilintide

Declaration of interest

MB Christensen is a minority shareholder of Antag Therapeutics Ap. The authors have no other 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 apart from those disclosed.

Reviewer disclosures

A reviewer on this manuscript has disclosed that they receive remuneration for services on speaker’s bureau, advisory boards and as co-chair of the SELECT Steering Committee for Novo Nordisk. They have also served as a scientific advisor to Lilly (Advisor, 2 years ago and not ongoing), Boeringer Ingelheim (Advisor, 1 year ago), Janssen (2 years ago and not ongoing), Sanofi (1 year ago and not ongoing). Peer reviewers on this manuscript have no other relevant financial relationships or otherwise to disclose.