Good Clinical Practice Office, Guang'anmen Hospital China Academy of Chinese Medical Sciences, Beijing, China.
Department of Endocrinology, Guang'anmen Hospital China Academy of Chinese Medical Sciences, Beijing, China.
JAMA Intern Med. 2024 Jul 1;184(7):727-735. doi: 10.1001/jamainternmed.2024.1190.
Previous studies have shown that Jinlida (JLD) granules, an approved treatment for type 2 diabetes in China, can reduce blood glucose level, reduce glycated hemoglobin (HbA1c), and improve insulin resistance in people with type 2 diabetes.
To evaluate the effect of long-term administration of JLD vs placebo on the incidence of diabetes in participants with impaired glucose tolerance (IGT) and multiple metabolic abnormalities.
DESIGN, SETTING, AND PARTICIPANTS: This multicenter, double-blind, placebo-controlled randomized clinical trial (FOCUS) was conducted across 35 centers in 21 cities in China from June 2019 to February 2023. Individuals aged 18 to 70 years with IGT and multiple metabolic abnormalities were enrolled.
Participants were randomly allocated 1:1 to receive JLD or placebo (9 g, 3 times per day, orally). They continued this regimen until they developed diabetes, withdrew from the study, were lost to follow-up, or died.
The primary outcome was the occurrence of diabetes, which was determined by 2 consecutive oral glucose tolerance tests. Secondary outcomes included waist circumference; fasting and 2-hour postprandial plasma glucose levels; HbA1c; fasting insulin level; homeostatic model assessment for insulin resistance (HOMA-IR); total cholesterol, low-density lipoprotein cholesterol, and triglyceride levels; ankle-brachial index; and carotid intima-media thickness.
A total of 889 participants were randomized, of whom 885 were in the full analysis set (442 in the JLD group; 443 in the placebo group; mean [SD] age, 52.57 [10.33] years; 463 [52.32%] female). Following a median observation period of 2.20 years (IQR, 1.27-2.64 years), participants in the JLD group had a lower risk of developing diabetes compared with those in the placebo group (hazard ratio, 0.59; 95% CI, 0.46-0.74; P < .001). During the follow-up period, the JLD group had a between-group difference of 0.95 cm (95% CI, 0.36-1.55 cm) in waist circumference, 9.2 mg/dL (95% CI, 5.4-13.0 mg/dL) in 2-hour postprandial blood glucose level, 3.8 mg/dL (95% CI, 2.2-5.6 mg/dL) in fasting blood glucose level, 0.20% (95% CI, 0.13%-0.27%) in HbA1c, 6.6 mg/dL (95% CI, 1.9-11.2) in total cholesterol level, 4.3 mg/dL (95% CI, 0.8-7.7 mg/dL) in low-density lipoprotein cholesterol level, 25.7 mg/dL (95% CI, 15.9-35.4 mg/dL) in triglyceride levels, and 0.47 (95% CI, 0.12-0.83) in HOMA-IR compared with the placebo group. After 24 months of follow-up, the JLD group had a significant improvement in ankle-brachial index and waist circumference compared with the placebo group.
The findings suggest that JLD can reduce the risk of diabetes in participants with IGT and multiple metabolic abnormalities.
Chinese Clinical Trial Register: ChiCTR1900023241.
重要性：既往研究表明，金芪降糖胶囊（JLD）是中国批准用于 2 型糖尿病的治疗药物，可降低血糖水平，降低糖化血红蛋白（HbA1c），并改善 2 型糖尿病患者的胰岛素抵抗。
目的：评估 JLD 与安慰剂长期治疗对糖耐量受损（IGT）和多种代谢异常患者糖尿病发病的影响。
设计、地点和参与者：这是一项多中心、双盲、安慰剂对照、随机临床试验（FOCUS），在中国 21 个城市的 35 个中心进行，从 2019 年 6 月至 2023 年 2 月招募了年龄在 18 至 70 岁、有 IGT 和多种代谢异常的个体。
干预：参与者随机 1:1 分配接受 JLD 或安慰剂（9g，每日 3 次，口服）。他们继续这种治疗方案，直到发生糖尿病、退出研究、失访或死亡。
主要结局和测量：主要结局是通过连续 2 次口服葡萄糖耐量试验确定的糖尿病发生情况。次要结局包括腰围；空腹和餐后 2 小时血糖水平；HbA1c；空腹胰岛素水平；稳态模型评估的胰岛素抵抗（HOMA-IR）；总胆固醇、低密度脂蛋白胆固醇和甘油三酯水平；踝臂指数；和颈动脉内膜-中层厚度。
结果：共有 889 名参与者被随机分配，其中 885 名进入全分析集（JLD 组 442 名；安慰剂组 443 名；平均[标准差]年龄 52.57[10.33]岁；463[52.32%]名女性）。在中位数为 2.20 年（IQR，1.27-2.64 年）的随访期间，与安慰剂组相比，JLD 组发生糖尿病的风险较低（风险比，0.59；95%CI，0.46-0.74；P<0.001）。在随访期间，JLD 组的腰围差值为 0.95cm（95%CI，0.36-1.55cm），餐后 2 小时血糖差值为 9.2mg/dL（95%CI，5.4-13.0mg/dL），空腹血糖差值为 3.8mg/dL（95%CI，2.2-5.6mg/dL），HbA1c差值为 0.20%（95%CI，0.13%-0.27%），总胆固醇差值为 6.6mg/dL（95%CI，1.9-11.2mg/dL），低密度脂蛋白胆固醇差值为 4.3mg/dL（95%CI，0.8-7.7mg/dL），甘油三酯差值为 25.7mg/dL（95%CI，15.9-35.4mg/dL），HOMA-IR 差值为 0.47（95%CI，0.12-0.83），与安慰剂组相比。随访 24 个月后，JLD 组的踝臂指数和腰围改善明显优于安慰剂组。
结论和相关性：研究结果表明，JLD 可降低 IGT 和多种代谢异常患者发生糖尿病的风险。
试验注册：中国临床试验注册中心：ChiCTR1900023241。
