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GLP-1 Analogs’ Effects on Regional Adiposity

Glucagon-like peptide 1 (GLP-1) analogs are effective for reducing fat storage in most body depots, according to a review of 45 clinical trials and a meta-analysis of 35 trials. This suggests efficacy of the agents for “combating metabolic, obesity-associated diseases via reductions of key [adipose tissue (AT)] depot volumes,” the authors conclude.

“Data on [total AT (TAT)] are quite convincing and strongly support a consistently moderate-to-large attenuating effect of GLP-1 analog treatment on total body fat content regardless of the study population or intervention specifics,” the authors write. “The biological significance of this endpoint is unclear because it does not reflect adiposity distribution, much like BMI; however, it is less influenced by muscle mass compared to BMI, and it was used here as an introductory proof-of-concept finding confirming an effect of GLP-1 analog treatment on adiposity.

“[Visceral AT (VAT)] is considered to be a major mediator of obesity complications via the promotion of systemic inflammation and pathogenic adipokine secretome. On the other hand, the relationship of [subcutaneous AT (SAT)] with cardiometabolic disease is more controversial, whereas it has been proposed that SAT may even have protective effects, acting as a more inert nutrient overload reservoir. Although GLP-1 analogs appeared to reduce VAT (and to a lesser degree SAT) in our meta-analysis, the effect sizes of the respective analyses are strongly influenced by [certain studies] as well as the liraglutide ≥2.4 mg dose arm of [one study]. [Two] studies suggest a potentially enhanced treatment effect in the context of the polycystic ovary syndrome, particularly regarding VAT, which is of no surprise given the complex endocrine effects of GLP-1 and the endocrine dysregulation accompanying the polycystic ovary syndrome. On the other hand, the striking treatment effects in [one study of] liraglutide 2.4 and 3 mg (the latter is used for obesity treatment) may reflect a dose–response effect. [Another study] included South Asian overweight participants with lower BMI compared to most other studies, suggesting that a larger treatment effect size could be observed in particular ethnic sub-groups or overweight patients with comparatively less obesity burden. Finally, it should be noted that SAT and VAT measures in most studies were performed mainly on abdominal imaging studies. VAT virtually exists in the abdominal viscera; it can also be observed to a lesser extent in the thoracic viscera, thus producing a small source of inaccuracy. Additionally, thoracic and extremity SAT may be underestimated.”

Source: Obesity Reviews