Effects of mirabegron on brown adipose tissue and metabolism in humans: A systematic review and meta-analysis

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Abstract
Background Brown adipose tissue (BAT) has emerged as a potential therapeutic target for metabolic disorders due to its thermogenic and anti-obesity properties. β3-adrenergic receptor (β3-AR) agonists have also gained attention as potential agents for BAT activation and metabolic regulation. Mirabegron, a selective β3-AR-agonist used clinically for overactive bladder syndrome, has been explored for its utility in metabolic disorders. However, the controversy surrounding the ability of mirabegron to activate BAT to accelerate metabolism requires further investigation. The aim of this systematic review is to characterize comprehensively the impact of mirabegron on human BAT and its metabolism. Methods We searched PubMed Central, Web of Science, Embase, and Cochrane Library databases for relevant papers published from the date of database inception to March 2023 for systematic reviews and meta-analyses. We extracted data on primary outcome indicators such as BAT volume, BAT activity, body temperature, and resting energy expenditure (REE), as well as secondary outcome indicators such as heart rate (HR), diastolic blood pressure (DBP), systolic blood pressure (SBP), non-esterified fatty acids (NEFA), blood glucose, and blood insulin from relevant studies. For studies that did not provide suitable data for meta-analysis, we used narrative data synthesis. For studies that provided suitable data for meta-analysis, we conducted meta-analysis using RevMan 5.4 software. Results We reviewed 10 papers and included 6 in our meta-analysis. Our findings revealed no significant changes in BAT volume (p = 0.72) or blood glucose (p = 0.52) with mirabegron when compared to the placebo or pre-dose population. However, patients showed significant increases in BAT activity (p < 0.01), blood NEFA (p < 0.01), body temperature (p < 0.01), REE (p < 0.01), HR (p < 0.01), DBP (p < 0.01), SBP (p = 0.25), and blood insulin (p < 0.01). Conclusion Through our meta-analysis of 6 papers, we found that mirabegron has the potential to increase human BAT activity, REE, NEFA content, body temperature, HR, blood pressure, and blood insulin content. These effects may lead to reductions in blood glucose levels in obese/overweight and diabetic patients. Additionally, the activation of BAT by mirabegron could represent a novel approach for treating obesity, diabetes, and cardiovascular disease. Trial registration number and date CRD42023413446, 04/11/2023.

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