As one of the most prevalent health problems worldwide, obesity imposes substantial public health and economic burdens, which have attracted increasing attention from patients, regulatory agencies, and biopharmaceutical companies.Currently, research and development efforts are actively exploring weight‑loss medications targeting different pathways in the pathophysiology of obesity.Although various anti‑obesity or glucose‑lowering agents have been widely used in clinical practice, systematic and direct comparative evidence on whether different medications differ in fat redistribution remains lacking.
A recent network meta‑analysis by the team led by Professors Guo Lixin and Pan Qi from Beijing Hospital, published in Obesity Reviews, demonstrated that sodium‑glucose cotransporter 2 inhibitors (SGLT‑2i) and glucagon‑like peptide‑1 receptor agonists (GLP‑1 RAs) contribute to the reduction of visceral adipose tissue (VAT) and may offer therapeutic advantages.Physicians can select appropriate weight‑loss medications based on patients’ fat distribution profiles.Dr. Qiao Xiuqi from Peking Union Medical College is the first author of this article.
According to World Health Organization estimates, approximately 39% of adults worldwide are overweight and 13% have obesity, with prevalence exceeding 40% in some regions.Obesity and overweight represent major global public health issues and are closely associated with multiple diseases, including type 2 diabetes mellitus (T2DM) and cardiovascular disease.In addition to obesity and atherosclerosis, insulin resistance is a hallmark of T2DM, and fat distribution plays a key role in determining individual insulin sensitivity.
Body fat is mainly distributed as VAT and subcutaneous adipose tissue (SAT), which exhibit distinct metabolic characteristics.Visceral fat is strongly linked to insulin resistance and dysregulated glucose and lipid metabolism.Its accumulation is also an important marker for assessing overall cardiovascular disease risk and significantly increases the risk of hypertension and ischemic heart disease.
Although several medications have been approved by the FDA for the treatment of obesity, systematic comparisons of their effects on fat distribution—especially VAT and SAT—remain insufficient.In general, various weight‑loss medications may modify body fat distribution by regulating lipid metabolism in different fat depots, thereby improving metabolic disorders and reducing the risk of macrovascular complications.However, the impact of weight‑loss medications on fat distribution has long been underappreciated.Therefore, this study conducted a systematic review and network meta‑analysis of relevant randomized controlled trials, focusing on outcomes related to fat distribution.
This network meta‑analysis systematically evaluated the effects of weight‑loss medications on body fat distribution.Although only 6 weight‑loss or metabolism‑related agents were included, results showed that, compared with other glucose‑lowering drugs or placebo, GLP‑1 RAs significantly reduced both VAT and SAT, as well as body weight and waist circumference, suggesting comprehensive advantages in remodeling fat distribution.
Accumulating evidence indicates that VAT plays a critical role in the development and progression of various metabolic diseases.Excess VAT not only disturbs adipokine secretion and participates in the pathogenesis of non‑alcoholic steatohepatitis and metabolic syndrome, but its high metabolic activity is also recognized as an important source of chronic inflammation in patients with obesity and coronary heart disease.Furthermore, VAT has been validated as an independent predictor of T2DM risk.Thus, for patients with T2DM, it is particularly important to select therapeutic strategies that improve glucose metabolism and reduce VAT.The findings of this study provide evidence‑based support for the role of GLP‑1 RAs in modifying fat distribution.
Regarding mechanisms of action, previous studies suggest that GLP‑1 RAs may influence fat distribution through multiple pathways.GLP‑1 receptor expression has been found to be higher in intra‑abdominal fat cells than in subcutaneous fat cells in obese diabetic patients, indicating that GLP‑1 RAs may induce lipolysis in fat cells by activating the receptor.Studies have shown that high concentrations of GLP‑1 enhance lipolysis in adipocytes, whereas low concentrations may promote adipogenesis.In addition, GLP‑1 delays gastric emptying, which may also contribute to the regulation of energy intake and body fat distribution.
This study also found that SGLT‑2 inhibitors significantly reduced VAT but had no statistically significant effect on SAT, with sensitivity analyses consistent with the overall conclusion.This finding differs from some previous studies, which may be related to the relatively short follow‑up duration of some trials included in this analysis.
Animal experiments suggest that SGLT‑2 inhibitors may promote lipolysis by activating the liver–brain–fat axis and initiating glycogen depletion signaling, while reducing GLUT4 expression in adipose tissue, shifting substrate utilization from lipid storage toward glucose oxidation.
As the first network meta‑analysis to systematically evaluate the effects of weight‑loss medications on VAT and SAT, this study provides new evidence‑based insights into the differences among various weight‑loss agents in fat distribution.However, further large‑scale, long‑term randomized controlled trials are needed to validate these findings.