New Guidelines Favor Semaglutide and Tirzepatide as First-Line Treatments for Obesity and Its Complications

Recent developments in obesity management emphasize the importance of targeted pharmacological therapy. The European Association for the Study of Obesity (EASO) has introduced a new framework published in Nature Medicine that recommends semaglutide and tirzepatide as first-line medications for treating obesity and most related complications.

According to the guidelines, despite the availability of various treatment options, semaglutide—a GLP-1 receptor agonist—and tirzepatide—a dual GIP and GLP-1 receptor agonist—stand out as the most effective agents for inducing substantial weight loss. Dr. Andreea Ciudin, co-first author of the framework, highlights that these medications should be prioritized in most cases due to their proven efficacy.

The new algorithm for obesity treatment is primarily guided by the presence or absence of obesity-related complications, allowing for more personalized therapy. The selection of medication considers the degree of weight loss needed, impact on specific complications, and safety profile. In cases where significant weight reduction is necessary, tirzepatide and semaglutide are recommended based on clinical trial data, including traditional and network meta-analyses.

The framework also distinguishes between different types of obesity-related diseases: "fat mass disease," such as obstructive sleep apnea (OSA) and osteoarthritis, and "sick fat disease," which includes conditions like prediabetes, type 2 diabetes, cardiovascular disease, heart failure, and metabolic dysfunction associated with liver disease.

For fat mass diseases, tirzepatide is suggested as the first choice for patients with obesity and OSA, although evidence currently relies on limited trials. Semaglutide shows superior results in reducing pain for obesity with osteoarthritis, making it the preferred treatment.

In managing sick fat diseases, tirzepatide and semaglutide are first-line options for prediabetes and type 2 diabetes with obesity. These drugs also reduce major cardiovascular events, supporting their use in patients with cardiovascular risk factors. However, in heart failure, the current evidence is limited, and either medication could be considered.

For hepatic complications like MASH, tirzepatide is recommended presently, but emerging research—such as the Phase III ESSENCE trial—suggests semaglutide may soon be added as a primary treatment option.

The authors underline the importance of considering economic factors and health system resources, emphasizing that early treatment of obesity can prevent serious end-organ damage. They acknowledge existing gaps in evidence regarding the full spectrum of these medications’ effects on various obesity-related conditions, though ongoing research continues to expand their potential benefits.

Experts stress that personalized treatment strategies should take into account patient-specific factors, including disease severity, comorbidities, socioeconomic context, and personal health goals. This framework aims to support clinicians in making evidence-based decisions while recognizing the evolving landscape of obesity pharmacotherapy.

Overall, the guidelines mark a significant shift towards more targeted, effective, and individualized treatment approaches in obesity care, driven by recent advances in GLP-1 and GIP receptor agonists.

For more information, the full framework is published in Nature Medicine (2025). Source: https://medicalxpress.com/news/2025-10-semaglutide-tirzepatide-line-treatment-obesity.html