GLP-1s from Novo, Lilly 'should be first-line in obesity'

The European Association for the Study of Obesity (EASO) has called for GLP-1 agonists from Novo Nordisk and Eli Lilly to be used first-line for people with obesity and most of its complications.

New guidelines from the organisation – published in Nature Medicine – recognise that while there are multiple options on the market, Novo Nordisk's GLP-1 drug Wegovy (semaglutide) and Lilly's dual GLP-1/GIP agonist Zepbound (tirzepatide) "are so effective that they should be the first choice in almost all cases," according to lead author Dr Andreea Ciudin of Spain's metabolic disorders institute CIBERDEM.

The recommendation reflects that the management of obesity "should not be limited to weight loss alone but should instead adopt a holistic approach that includes the prevention, resolution or improvement of complications, enhanced mental well-being, physical fitness, social functioning, and overall health and quality of life," according to the paper.

It also concludes that, when the need for weight loss on health grounds is not so acute, other drugs can be considered – including Novo Nordisk's older GLP-1 agonist liraglutide, naltrexone–bupropion, and phentermine-topiramate.

The guideline recommends specific drugs for patients, depending on the obesity-related complications they are living with, in a personalised approach.

They have separated these complications into two broad categories, specifically fat mass disease, which is associated with physical problems like osteoarthritis and obstructive sleep apnoea (OSA), and sick-fat disease, characterised by prediabetes and heart and liver diseases.

Semaglutide should be considered first for knee osteoarthritis and tirzepatide for OSA, they recommend. Meanwhile, the data support semaglutide for people with a history of heart disease, tirzepatide for non-alcoholic fatty liver disease (NAFLD), and either drug if patients have prediabetes/type 2 diabetes and/or heart failure.

The EASO notes that the guideline was prepared before Novo Nordisk's recent approval for Wegovy in metabolic dysfunction-associated steatotic hepatitis (MASH), and future updates are likely to include the drug as a first-line option in this setting.

It also points to emerging data for the GLP-1 class in other indications, including chronic kidney disease, neurodegenerative disorders, polycystic ovary syndrome, certain cancers, and mental health conditions, that may further strengthen the case for GLP-1-based drugs as the go-to weight-loss therapy, and has promised to update the guideline regularly.

"Although no treatment algorithm can replace the nuanced clinical judgment required for such comprehensive assessments, this tool can serve to support therapeutic decision-making in obesity," said Ciudin. "This new class of GLP-1 agonists and GIP/GLP-1 dual agonists is completely transforming care of obesity and its complications."

Co-lead author Prof Barbara McGowan of Guys & St Thomas's Hospital NHS Foundation Trust in the UK stressed that tailoring treatment to the individual "is a complex task that must consider several factors, including the severity of adiposity, the presence and extent of complications, comorbidities and concurrent therapies. Socioeconomic context, patient values, expectations, and personal goals must also be considered."

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