Berberine and Adiposity in Diabetes-Free Individuals With Obesity and MASLD
Lubi Lei, B. Wang, Lingshan Zhao, Jingkuo Li, Xiaofang Yan, Jiandong Jiang, Lulu Wang, Gang Ren, Yinchu Li, Xiaoguang Cheng, Xiaoyan Yan, Yidan Zhu, Guo Yuanlin, Hui Zhong, Haibo Zhang, Jie Li, BRAVO Collaborative Group, Xiaojian Liu, Yinming Bai, Hui Zheng, Yong Liu, Yaqin Liu, Yang Zheng, Hailin Zhang, Xibo Fang, Yihua Yu, Xiaoxuan Yin, Gong Cheng, Guojiong Jia, Miaomiao Jin, Yuxue Guo, Xiuling Zhang, Dandan He, Zhen Li, Wenjing Hao, Liting Guo, Xia Guo, Jiamian Chen, Rui Hu, Xuefen Li, Jing He, Fangjie Ji, Xiangying Meng, Yi Zhao, XINHONG LIU, Xu Wang, Hao Wang, Jie Li, Xiaoguo Zhang, Xiao Gao, Yingyin Feng, Meizi He, Shiqi Ren, Guiying Shi, Min Yu, Kunjiang Bai, Xia Wang, Weihui Li, Zhaoxi Liu, Lin Zou, Sai Jiang, Jingyu Wang, Xiaodong Li, Wanyue Zhang, Yanfang Hou, Hui Yang, Haibo Zhu, Huijun Lin, Jianfeng Wang, Qian Zhang, Guisheng Zhang, Xiaohong Liu, Ning Wang, Mingjian Zhu, Dan Wang, Qiqi Meng, Yueqing Pi, Shuangli Zhao, Yan Wang, Changyun Zhao, Feifei Ye, Xiaoli Zhou, Jianhua Mao, Ming Li, Hui Zhao, Chenyuan Liang, Xingtao Feng, Xuemei Zhang, Rong Jiang, Nannan Chen, Xiaoxiu Dou, Tiantian Zhao, Tiantian Ma, Qiaojuan Ma, Jieli Pan, Jing Lv, Yong Dang, Long Yu, Ruibin Liu, Wan Zhou
Abstract
Importance: Berberine is a potential therapy for metabolic disorders, yet its effects on visceral adipose tissue (VAT) and liver fat remain uncertain. Objectives: To evaluate the efficacy and safety of berberine in reducing VAT area and liver fat content in diabetes-free individuals with obesity and metabolic dysfunction-associated steatotic liver disease (MASLD). Design, Setting, and Participants: In this multicenter, double-blind randomized clinical trial, diabetes-free individuals with obesity and MASLD were enrolled at 11 hospitals in China between July 6 and December 29, 2023, with a follow-up duration of 6 months. Interventions: Participants were randomly assigned to receive either oral berberine, 1 g/d, or a matching placebo. Main Outcomes and Measures: The primary outcomes were relative percentage change in VAT area and absolute change in liver fat content assessed by computed tomography. Other outcomes included changes in parameters of glucose, lipids, and inflammation. Analyses were conducted according to the intention-to-treat principle. Results: Among 337 randomized participants (mean [SD] age, 41.8 [10.6] years; 221 [65.6%] male), 169 received berberine and 168 placebo. The mean (SD) medication adherence rates were 90.3% (14.7%) for berberine and 90.7% (17.4%) for placebo. No significant differences were observed between study arms for VAT area (1.4% [97.5% CI, -2.4% to 5.2%]) or liver fat content (0.9% [97.5% CI, -0.4% to 2.1%). Berberine was associated with larger reductions in low-density lipoprotein cholesterol (-7.72 [95% CI, -13.13 to -1.93] mg/dL), apolipoprotein B (-3.42 [95% CI, -6.33 to -0.51] mg/dL) and high-sensitivity C-reactive protein (hs-CRP) (-0.072 [95% CI, -0.140 to -0.004] mg/dL) vs placebo, but not other secondary outcomes. The incidence of adverse events was similar between study arms. Post hoc analyses suggested consistent patterns of larger reductions in low-density lipoprotein cholesterol, apolipoprotein B, and hs-CRP levels in participants with higher baseline hs-CRP levels. Conclusions and Relevance: In this randomized clinical trial of diabetes-free individuals with obesity and MASLD, a 6-month berberine treatment at a daily dose of 1 g had an excellent safety profile but did not reduce VAT area or liver fat content. Trial Registration: ClinicalTrials.gov Identifier: NCT05647915.