Treatment of obesity with medications binding the glucagon-like peptide 1 receptor: what is the current state of play?

ABSTRACT

Introduction

Obesity, marked by abnormal fat accumulation, poses significant health risks, necessitating effective therapeutic interventions. The focus of this review is to elucidate the importance of glucagon-like peptide 1 (GLP-1) receptor-binding medications in addressing obesity-related health deteriorations.

Areas covered

Exploring the mechanisms, efficacy, and safety profiles, this review comprehensively assesses medications selectively or non-selectively binding the GLP-1 receptor for obesity treatment. A meticulous analysis of phase 2 and phase 3 data positions retatrutide, CagriSema, survudotide, tirzepatide, semaglutide, and liraglutide in order of effectiveness. While showcasing their efficacy and safety, the review acknowledges the ongoing phase 3 studies, highlighting the need for further exploration of contraindications, dosage, and potential adverse effects to inform personalized treatment decisions.

Expert opinion

The ongoing anticipation of long-term benefits, particularly sustained weight loss and cardiovascular outcomes, underscores the significance of future treatment algorithms for addressing the disease of obesity.

KEYWORDS:

• Obesity
• GLP-1 receptor agonists
• GIP receptor agonist
• adverse effects
• pharmacological therapy

Article highlights

• The SURMOUNT-1 trial investigated tirzepatide’s impact on weight loss in individuals with obesity, demonstrating promising results over a 72-week period

• Orlistat (Xenical, Alli) is an FDA and EMA-approved gastric and pancreatic lipase inhibitor, with associated side effects such as oily rectal leakage and abdominal distress.

• Higher doses of certain GLP-based drugs have shown superior effectiveness compared to lower doses, as evidenced in the treatment of type 2 diabetes. Dulaglutide has been identified as a relevant medication in the context of GLP-based drug treatment for obesity.

• Patients undergoing treatment with GLP-based drugs are encouraged to maintain a daily caloric deficit and increase physical activity to support weight loss efforts.

• The therapeutic landscape for GLP/GIP agonist drugs, including medications such as tirzepatide, is poised for transformation, with a focus on cardiovascular outcomes and overall health improvement.

Declaration of interest

C Le Roux reports grants from the Irish Research Council, Science Foundation Ireland, Anabio, and the Health Research Board. He serves on advisory boards and speakers’ panels of Novo Nordisk, Herbalife, GI Dynamics, Eli Lilly, Johnson & Johnson, Glia, Irish Life Health, and Boehringer Ingelheim, Currax, Zealand Pharma, and Rhythm Pharma. C Le Roux is a member of the Irish Society for Nutrition and Metabolism outside the area of work commented on here. He was the chief medical officer and director of the Medical Device Division of Keyron in 2021. Both of these are unremunerated positions. C Le Roux was a previous investor in Keyron, which develops endoscopically implantable medical devices intended to mimic the surgical procedures of sleeve gastrectomy and gastric bypass. No patients have been included in any of Keyron’s studies, and they are not listed on the stock market. C Le Roux was gifted stock holdings in September 2021 and divested all stock holdings in Keyron in September 2021. He continues to provide scientific advice to Keyron for no remuneration. He also provides obesity clinical care in the Beyond BMI clinic and is a shareholder in the clinic.

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

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

Additional information

Funding

This paper was not funded.