By Don Tracy, Associate Editor

Findings from a study published in the Journal of the Obesity Society may significantly advance the understanding of GLP-1 analogues and their role in treating obesity.In recent years, glucagon-like peptide-1 (GLP-1) analogues, such as Ozempic, have demonstrated promising weight loss results by promoting satiety and delaying gastric emptying, thus reducing energy intake. However, a number of studies conducted in animals suggest that GLP-1 therapies may also influence energy expenditure by increasing metabolic activity in visceral adipose tissue (VAT), a more metabolically active and harmful fat depot compared to subcutaneous fat. The study’s primary objective was to determine whether VAT metabolic activation also occurs in humans and how it contributes to the weight loss effect of GLP-1 analogues.1
“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. 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,” said Donal O’Shea, study author, in a press release.2
The proof-of-concept, randomized controlled trial included 30 non-diabetic individuals with obesity (BMI 30-40 kg/m²) and moderate-to-severe obstructive sleep apnea (OSA). As part of the study, participants were randomly assigned to receive either GLP-1 analogue therapy (using liraglutide at a 3 mg/day dose), CPAP therapy, or a combination of both. The researchers employed 18F-fluorodeoxyglucose (18F-FDG) PET-CT imaging to measure the metabolic activity of VAT over a 24-week period, expressed as the target-to-background ratio (TBR), both at baseline and upon study completion.
Results found that GLP-1 treatment resulted in a significant increase in VAT metabolic activity (measured by TBR), while continuous positive airway pressure (CPAP) alone did not. Additionally, results indicated that weight loss connects to VAT activity, suggesting that the activation of VAT metabolism may contribute to the overall weight reduction effect of GLP-1 therapy, according to the study authors. Further, investigators noted that participants with lower baseline VAT metabolic activity experienced greater weight loss with GLP-1 therapy, suggesting that baseline VAT activity could serve as a predictive marker for identifying those who may benefit most from GLP-1-based treatment. Lastly, combination treatment with GLP-1 and CPAP demonstrated a modest effect in VAT metabolic activity compared to solo GLP-1 therapy.1
“Safe medical treatment for obesity is still in its infancy and we need to understand fully how the treatment works. Understanding how these agents increase energy burn should be an important part of future research. I hope the companies involved in the development of these treatments will examine this area in more detail because these are very expensive studies to carry out and we are very grateful to the Health Research Board and University College Dublin for supporting it,” said O’Shea, in the press release.
The authors of the study suggest that these findings will significantly advance the understanding of GLP-1 analogues and their role in treating obesity. Moving forward, the authors suggest that future studies should include more diverse populations, with different control arms needed to validate these findings and further elucidate the specific pathways involved in VAT metabolic activation.1
“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,” concluded O’Shea, in the press release.