Department of Endocrinology, Henan Provincial Key Medicine Laboratory of Intestinal Microecology and Diabetes, Henan Provincial People's Hospital, People's Hospital of Zhengzhou University, Zhengzhou, Henan 450003, China.
State Key Laboratory of Microbial Metabolism and Ministry of Education Key Laboratory of Systems Biomedicine, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai 200240, China.
J Clin Endocrinol Metab. 2022 Jun 16;107(7):1888-1896. doi: 10.1210/clinem/dgac210.
Cardiovascular benefits of empagliflozin in patients with type 2 diabetes mellitus (T2DM) have been reported; however, the underlying mechanism remains unknown.
We hypothesized that the cardiovascular benefits of empagliflozin are associated with altered gut microbiota and plasma metabolites, and that empagliflozin may be used as an initial treatment for patients with T2DM at risk of cardiovascular diseases (CVDs).
This randomized, open-label, 3-month, 2-arm clinical trial included 76 treatment-naïve patients with T2DM and risk factors for CVD who were treated with either empagliflozin (10 mg/d, n = 40) or metformin (1700 mg/d, n = 36). We investigated changes in clinical parameters related to glucose metabolism and CVD risk factors, gut microbiota using 16S rRNA gene sequencing, and plasma metabolites using LC-MS.
We found significant and similar reduction in HbA1c levels and alleviation of glucose metabolism in both groups. However, only empagliflozin improved CVD risk factors. Empagliflozin significantly reshaped the gut microbiota after 1 month of treatment; this alteration was maintained until the end of the trial. Empagliflozin increased the levels of plasma metabolites such as sphingomyelin, but reduced glycochenodeoxycholate, cis-aconitate, and uric acid levels. Concurrently, empagliflozin elevated levels of short-chain fatty acid-producing bacteria such as species from Roseburia, Eubacterium, and Faecalibacterium, and reduced those of several harmful bacteria including Escherichia-Shigella, Bilophila, and Hungatella.
Empagliflozin may be a superior initial therapy for patients with T2DM at risk of CVDs; its cardiovascular benefits may be associated with shifts in gut microbiota and plasma metabolites.
恩格列净可改善 2 型糖尿病（T2DM）患者的心血管结局，但具体机制尚不清楚。
我们假设恩格列净的心血管获益与肠道菌群和血浆代谢物的改变有关，且恩格列净可作为心血管疾病（CVD）风险患者的起始治疗药物。
这是一项随机、开放标签、3 个月、2 臂临床试验，纳入了 76 例初治 T2DM 且有 CVD 风险的患者，他们分别接受恩格列净（10 mg/d，n=40）或二甲双胍（1700 mg/d，n=36）治疗。我们研究了与葡萄糖代谢和 CVD 危险因素相关的临床参数、使用 16S rRNA 基因测序的肠道菌群以及使用 LC-MS 的血浆代谢物的变化。
我们发现两组患者的 HbA1c 水平均显著降低，血糖代谢均得到改善。但仅恩格列净可改善 CVD 危险因素。恩格列净治疗 1 个月后可显著重塑肠道菌群，且该改变可维持至试验结束。恩格列净可增加血浆代谢物如神经鞘磷脂的水平，但降低甘胆酸、顺乌头酸和尿酸的水平。同时，恩格列净可增加罗伊氏乳杆菌、真杆菌和粪杆菌等产生短链脂肪酸的细菌的水平，降低大肠埃希菌-志贺菌属、拟杆菌属和哈氏弧菌属等有害细菌的水平。
恩格列净可能是 CVD 风险 T2DM 患者的更佳起始治疗药物；其心血管获益可能与肠道菌群和血浆代谢物的改变有关。
