Liu Renjiao, Hou Dangmin, Leng Mingxin, Li Zhouhuiling, Zhang Yifang, Liu Lingling, Wang Xincheng, Li Chunjun
Health Management Center, Tianjin Union Medical Center, The First Affiliated Hospital of Nankai University, No. 190 of Jieyuan Road, Hongqiao District, Tianjin, 300121, China.
Graduate School, Tianjin Medical University, Tianjin, China.
Diabetol Metab Syndr. 2025 Jul 18;17(1):286. doi: 10.1186/s13098-025-01765-x.
To observe the effect of glucagon-like peptide-1 receptor agonists (GLP-1RA) combined with metformin and metformin monotherapy on proinsulin changes in patients with obesity following weight loss. To explore whether the changes of proinsulin were related to GLP-1RA or secondary to weight reduction.
100 adults with obesity (BMI ≥ 28 kg/m) were randomized to 24-week treatment with liraglutide plus metformin (GLP-1RA group, n = 50) or metformin alone (1500 mg/day; control group, n = 50). All participants received standardized lifestyle interventions, including a 500 kcal/day energy-deficit diet and 150 min/week moderate intensity aerobic exercise. Visceral fat area (VFA) and body fat percentage (PBF) were measured using multifrequency bioelectrical impedance analysis (InBody770; Biospace Inc., Korea). Proinsulin levels were quantified via a chemiluminescent enzyme-linked immunosorbent assay (Human Proinsulin ELISA Kit, BayBio). Multiple regression analyses were applied to adjust for age, gender, baseline BMI, and treatment allocation, isolating weight loss effects from direct drug actions.
The weight, blood lipids and glucose metabolism indexes of two groups were significantly improved, and the effects were more significant in the GLP-1RA group. Correlation analysis showed that proinsulin change was positively correlated with body weight change and VFA change, which persisted after adjusting for confounding factors such as age, gender, baseline body mass index (BMI), and GLP-1RA medication.
GLP-1RA demonstrate superior weight loss effects and improvements in lipid and glucose metabolism in patients with obesity. However, the reduction in proinsulin levels is primarily attributed to the magnitude of weight loss itself, independent of GLP-1RA use.
观察胰高血糖素样肽-1受体激动剂（GLP-1RA）联合二甲双胍与二甲双胍单药治疗对肥胖患者减重后胰岛素原变化的影响。探讨胰岛素原变化是与GLP-1RA有关还是继发于体重减轻。
100例肥胖成年人（BMI≥28kg/m²）被随机分为两组，分别接受24周的利拉鲁肽联合二甲双胍治疗（GLP-1RA组，n = 50）或二甲双胍单药治疗（1500mg/天；对照组，n = 50）。所有参与者均接受标准化生活方式干预，包括每天500千卡的能量亏空饮食和每周150分钟的中等强度有氧运动。使用多频生物电阻抗分析仪（InBody770；韩国Biospace公司）测量内脏脂肪面积（VFA）和体脂百分比（PBF）。通过化学发光酶联免疫吸附测定法（人胰岛素原ELISA试剂盒，BayBio）对胰岛素原水平进行定量。应用多元回归分析调整年龄、性别、基线BMI和治疗分配因素，以分离体重减轻效应与药物直接作用。
两组的体重、血脂和糖代谢指标均显著改善，且GLP-1RA组效果更显著。相关性分析表明，胰岛素原变化与体重变化和VFA变化呈正相关，在调整年龄、性别、基线体重指数（BMI）和GLP-1RA用药等混杂因素后依然成立。
GLP-1RA在肥胖患者中显示出卓越的减重效果以及对脂质和糖代谢的改善作用。然而，胰岛素原水平的降低主要归因于体重减轻本身的幅度，与GLP-1RA的使用无关。
