Glucagon-like Receptor-1 agonists for obesity: Weight loss outcomes, tolerability, side effects, and risks.

Maria D Hurtado, Wissam Ghusn

Journal: Obesity pillars 2024;12():100127

PMID: 39286601

Free Full Text on Elsevier Science View on PubMed

Plain Language Summary

Glucagon-like peptide-1 receptor agonists and glucose-dependent insulinotropic polypeptide receptor agonists have shown great results as drugs for medical weight loss. However, little is known about the safety, tolerability, and health risks associated with these drugs. This review examines GLP-1RAs, such as liraglutide, semaglutide, and tirzepatide and discusses how effective these drugs are for weight loss, as well as their side effects and risks. The authors gathered data from various sources, including clinical trials and systematic reviews.

The findings indicate that GLP-1RAs can lead to significant weight loss, with liraglutide resulting in about 5% weight loss compared to placebo, semaglutide achieving around 12%, and tirzepatide achiveing about 18%. However, many users experienced gastrointestinal (related to the stomach and intestines) side effects.

It was concluded that whilst GLP-1RAs are effective for weight loss, they are associated with gastrointestinal side effects and rare but serious adverse events. This study could be used by healthcare professionals to understand the effectiveness and risks associated with GLP-1RAs for weight loss in individuals with obesity.

Abstract

BACKGROUND

This review investigates the side effects of glucagon-like peptide-1 receptor agonists (GLP-1RAs) like liraglutide, semaglutide, and tirzepatide, medications known for their efficacy in promoting weight loss among individuals with obesity. The rationale is rooted in understanding the balance between their therapeutic benefits and associated risks.

METHODS

This was a comprehensive clinical review, including systematic reviews, meta-analyses, randomized controlled trials (RCTs), and cohort studies. Data were extracted from databases such as PubMed, Scopus, Embase, MEDLINE, and Google Scholar, focusing on the tolerability, severity, and risks of these medications.

RESULTS

GLP-1RAs demonstrated significant weight loss outcomes. In clinical trials, liraglutide showed a placebo-corrected weight loss of around 5 %, semaglutide 12 %, and tirzepatide 18 %. Common side effects were predominantly gastrointestinal, including nausea, diarrhea, constipation, and vomiting. Rare serious adverse events included gallbladder disorders and acute pancreatitis. In, addition, multiple studies identify new risks associated with GLP-1RAs including increased aspiration risk during anesthesia due to delayed gastric emptying and challenges with bowel preparation for colonoscopies.

CONCLUSION

While GLP-1RAs are effective in managing obesity, their use is associated with gastrointestinal side effects and rare but serious adverse events. The findings underscore the importance of individualized dosing and thorough patient assessment. Continuous research and vigilant monitoring are essential to optimize their safe use. Further studies are needed to refine guidelines, particularly regarding new concerns such as delayed gastric emptying and its implications for anesthesia.

Address: Internal Medicine Department, Boston Medical Center, Boston, MA, USA.; Precision Medicine for Obesity Program, Division of Gastroenterology and Hepatology, Department of Medicine, Mayo Clinic, Rochester, MN, USA.; Division of Endocrinology, Diabetes, Metabolism, and Nutrition, Department of Medicine, Mayo Clinic, Jacksonville, FL, USA.

DOI: 10.1016/j.obpill.2024.100127