Tian Jinxia, Yang Yanfei, Yu Zijuan, Gao Yang, Zong Xiaochun, Wu Qiaojuan, Su Haiyan, Cao Wenjuan, Xu Dandan
The First Department of Endocrinology, Zhangjiakou First Hospital, Zhangjiakou, 075000, Hebei, China.
Department of Internal Medicine, Zhangjiakou First Hospital, Zhangjiakou, 075000, Hebei, China.
Hormones (Athens). 2025 Apr 11. doi: 10.1007/s42000-025-00649-z.
This randomized controlled trial aimed to compare the effects of dulaglutide alone versus dulaglutide combined with probiotics on cardiovascular risk factors, pancreatic beta-cell function, and gut microbiota in patients with type 2 diabetes mellitus (T2DM).
Sixty overweight/obese adults with T2DM (HbA1c 6.5-11%, BMI ≥ 24 kg/m²) were randomized to a control group (dulaglutide 1.5 mg/week + placebo) or an intervention group (dulaglutide 1.5 mg/week + probiotics containing Bifidobacterium longum, 2 × 10⁹ CFU/dose) for 12 weeks. Outcomes included glycemic control (HbA1c, fasting plasma glucose [FPG], 2-hour postprandial glucose [2hPG]), inflammatory markers (TNF-α, CRP), cardiovascular risk factors (blood pressure, lipids), gut microbiota, and safety.
The intervention group showed greater reductions in HbA1c (- 1.06% vs. -0.35%, P = 0.028), FPG (- 4.16 vs. -3.92 mmol/L, P = 0.010), and inflammatory markers (TNF-α: -43.6% vs. -33.3%, P < 0.001). Pancreatic beta-cell function improved significantly (HOMA-β: +34.7% vs. +23.1%, P = 0.034), with increased beneficial gut microbiota (Lactobacillus: +2.1 × 10⁶ vs. +1.3 × 10⁶ CFU/g, P < 0.001). Hypertension incidence (0% vs. 13.3%, P = 0.038) and dyslipidemia (0% vs. 16.7%, P = 0.020) were lower in the intervention group. Both regimens were well-tolerated, with no severe hypoglycemia or renal/hepatic toxicity.
Combining dulaglutide with probiotics enhances glycemic control, reduces inflammation, and improves cardiovascular risk factors in T2DM more effectively than dulaglutide alone, likely through gut microbiota modulation. This dual approach offers a promising strategy for T2DM management, though larger long-term trials are needed to confirm cardiovascular benefits.
本随机对照试验旨在比较度拉糖肽单药治疗与度拉糖肽联合益生菌对2型糖尿病（T2DM）患者心血管危险因素、胰岛β细胞功能和肠道微生物群的影响。
60例超重/肥胖的T2DM成人患者（糖化血红蛋白[HbA1c]为6.5 - 11%，体重指数[BMI]≥24kg/m²）被随机分为对照组（度拉糖肽1.5mg/周 + 安慰剂）或干预组（度拉糖肽1.5mg/周 + 含有长双歧杆菌的益生菌，2×10⁹CFU/剂量），为期12周。观察指标包括血糖控制（HbA1c、空腹血糖[FPG]、餐后2小时血糖[2hPG]）、炎症标志物（肿瘤坏死因子-α、C反应蛋白）、心血管危险因素（血压、血脂）、肠道微生物群及安全性。
干预组在HbA1c（-1.06%对-0.35%，P = 0.028）、FPG（-4.16对-3.92mmol/L，P = 0.010）和炎症标志物（肿瘤坏死因子-α：-43.6%对-33.3%，P < 0.001）方面降低幅度更大。胰岛β细胞功能显著改善（胰岛素抵抗指数[HOMA-β]：+34.7%对+23.1%，P = 0.034），有益肠道微生物群增加（乳酸杆菌：+2.1×10⁶对+1.3×10⁶CFU/g，P < 0.001）。干预组高血压发病率（0%对13.3%，P = 0.038）和血脂异常（0%对16.7%，P = 0.020）较低。两种治疗方案耐受性良好，均未出现严重低血糖或肾/肝毒性。
度拉糖肽联合益生菌比单用度拉糖肽更有效地增强了T2DM患者的血糖控制、减轻炎症并改善心血管危险因素，可能是通过调节肠道微生物群实现的。这种双重治疗方法为T2DM管理提供了一种有前景的策略，不过需要更大规模的长期试验来证实其对心血管的益处。
