SGLT2 inhibitors reduce epicardial adipose tissue more than GLP‐1 agonists or exercise interventions in patients with type 2 diabetes mellitus and/or obesity: A systematic review and network meta‐analysis

Abstract Background Epicardial adipose tissue (EAT) plays a significant role in several cardiovascular diseases. As a correctable risk factor and potential therapeutic target, reducing EAT has multiple cardiovascular benefits, especially in those with abnormal glucolipid metabolism. The objective of this research was to compare the effects of sodium–glucose cotransporter 2 (SGLT2) inhibitors, glucagon‐like peptide‐1 (GLP‐1) agonists, and exercise on the thickness of EAT and indicators of glucolipid metabolism in people with type 2 diabetes mellitus (T2DM), obesity, and T2DM with obesity. Methods We searched four electronic databases: PubMed, EMBASE, the Cochrane Library, and Web of Science for articles before 31 January 2024, regardless of language. We included randomized controlled trials and a small number of case–control studies in this network meta‐analysis. Differences in mean changes in EAT, body mass index, and glucolipid metabolism‐related metrics were assessed. Results A comprehensive analysis was conducted on 16 trials (15 randomized controlled trials and one case–control study), comprising a total of 867 people. SGLT2 inhibitors were significantly better at reducing EAT than placebo (standard mean different [SMD] = −0.85 cm [95% confidence interval (CI) −1.39, −0.31]); a similar result was observed for exercise compared with placebo (SMD = −0.78 cm [95% CI −1.37, −0.18]). SGLT2 inhibitors were also significantly better at reducing EAT than GLP‐1 agonists and conventional hypoglycaemic therapy (e.g., metformin or insulin; SMD = −0.74 cm [95% CI −1.45, −0.02] and SMD = −1.69 cm [95% CI −2.38, −0.99], respectively). SGLT2 inhibitors were significantly better than placebo at reducing body mass index (MD = −0.90 kg/m 2 [95% CI −1.14, −0.66]) and glycosylated haemoglobin (MD = −0.52% [95%CI −0.86, −0.18]). A similar result was observed when comparing GLP‐1 agonists and placebo (MD = −0.48% [95% CI −0.93, −0.03]). Changes in total cholesterol, low‐density lipoprotein cholesterol, and high‐density lipoprotein cholesterol were not statistically significant between interventions. Conclusion SGLT2 inhibitors have a distinct advantage over both placebo and other therapies at lowering EAT thickness, a result supported by direct comparisons and surface under the cumulative ranking curve analysis. Therefore, SGLT2 inhibitors should be prioritized as a treatment to reduce EAT in individuals with aberrant glucolipid levels, such as patients with T2DM and/or obesity.