A small new study from Irish researchers at St. Vincent’s University Hospital (SVUH) challenges that belief, however.
A randomized, controlled trial with 30 patients examined GLP-1 RAs, such as Ozempic, Wegovy, and Mounjaro. The findings, which were published in the journal Obesity, suggested a strong link between the increase in metabolic activity caused by once-daily treatment with GLP-1 and the amount of weight lost. Those who benefited the most were the patients with low metabolic activity to begin with, according to the researchers.
“This study challenges the main narrative about these newer treatments which is that they simply make you eat less, and that any action on energy burn is minimal,” explained Donal O’Shea, MB, Bch, BAO, MD, of SVUH and University College Dublin School of Medicine. “The strength of the association is surprising given the relatively small numbers studied and suggests this increase in metabolic activity is a significant contributor to how these drugs work.”
GLP-1 analogues are currently the most widely used pharmacotherapies for weight loss, according to background information in the article. “Their primary mechanism of action is attributed to reduction in energy intake,” the researchers wrote. “Data from murine studies also support an additional impact of those agents on energy homeostasis through upregulation of visceral adipose tissue (VAT) metabolic activity, but this remains uncertain in humans.”
The researchers’ proof-of-concept study was conducted on patients with obstructive sleep apnea and obesity who were randomized to a GLP-1 therapy-based weight-loss regimen, continuous positive airway pressure, or a combination of both for 24 weeks. At baseline and study completion, the study team performed 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography-computed tomography (PET-CT) to evaluate VAT metabolic activity, expressed as VAT target-to-background ratio.
The results indicated that treatment with GLP-1, but not with continuous positive airway pressure, was associated with a significant increase in VAT target-to-background ratio. “There was a strong correlation between the increase in VAT metabolic activity and the degree of weight loss,” the authors point outed, adding, “These data support the hypothesis that upregulation of VAT metabolic activity by GLP-1 contributes to its weight loss action in humans, and this subject warrants further detailed investigation.”
“Safe medical treatment for obesity is still in its infancy and we need to understand fully how the treatment works,” Dr. O’Shea advised. “Understanding how these agents increase energy burn should be an important part of future research.”
Dr. O’Shea added, “It always seemed oversimplistic to me that these new treatments were just making people eat less. So, this study finding is an exciting step forward in our understanding of how these new medicines for obesity work. The findings also provide science to support the fact that the treatment of obesity is not simply to eat less and move more—that’s the prevention piece—treatment is more complex than that.”
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