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胰高血糖素样肽-1受体激动剂联合胰岛素治疗成人肥胖2型糖尿病的综合疗效及安全性评价

Assessment of the efficacy and safety of glucagon-like peptide-1 receptor agonists combined with insulin therapy for obese adults with type 2 diabetes mellitus

    摘要
  • 摘要:
    目的 系统评价胰高血糖素样肽-1受体激动剂（GLP-1RA）联合胰岛素治疗成人肥胖2型糖尿病的疗效及安全性。
    方法 检索PubMed、Embase、The Cochrane Library、Web of Science、中国生物医学文献、维普、万方和中国知网数据库相关的随机对照试验，并采用RevMan 5.4软件进行荟萃分析。
    结果 纳入34项研究共计4 180例患者。荟萃分析结果显示，联合治疗组的体质量（体重）指数、糖化血红蛋白A1c（GHbA1c）、空腹血糖（FBG）、餐后2 h血糖（2 h BG）、总胆固醇（TC）、甘油三酯（TG）、低密度脂蛋白胆固醇（LDL-C）水平、低血糖风险均较单用胰岛素组低（P ＜ 0.05），高密度脂蛋白胆固醇（HDL-C）水平、恶心风险较单用胰岛素组高（P ＜ 0.05）。亚组分析结果显示，与单用胰岛素组比较，联合组的 GHbA1c水平均较低（均P ＜ 0.05）；除GLP-1RA联合门冬胰岛素组外，其他联合组的FBG水平均较低（均P ＜ 0.01）；除GLP-1RA联合门冬胰岛素+甘精胰岛素组外，其他联合组的2 h BG水平均较低（均P ＜ 0.01）。血脂方面，与单用胰岛素组比较，除GLP-1RA联合地特胰岛素或门冬胰岛素+甘精胰岛素组外，其他联合组的TC水平均较低（均P ＜ 0.01）；除GLP-1RA联合常规胰岛素或门冬胰岛素+甘精胰岛素组外，其他联合组的TG水平均较低（均P ＜ 0.05）；除GLP-1RA联合门冬胰岛素组外，其他联合组的LDL-C水平均较低（均P ＜ 0.05）；除GLP-1RA联合地特胰岛素组外，其他联合组的HDL-C水平均较高（均P ＜ 0.01）。
    结论 GLP-1RA联合胰岛素治疗可改善成人肥胖2型糖尿病患者的血糖、体重及血脂水平，降低低血糖风险，其疗效受联合使用的胰岛素类型影响。

     

    Abstract:
    Objective  To systematically assess the efficacy and safety of combining glucagon-like peptide-1 receptor agonists (GLP-1RA) with insulin in obese adult patients with type 2 diabetes mellitus (T2DM).
    Methods Randomized controlled trials were searched from PubMed, Embase, The Cochrane Library, Web of Science, China Biology Medicine, Chongqing VIP, Wanfang, and China National Knowledge Infrastructure databases. Meta-analysis was conducted using RevMan 5.4 software.
    Results A total of 34 studies involving 4180 patients were included. Meta-analysis demonstrated that compared to insulin monotherapy, the combination therapy group exhibited significant reductions in body mass index (BMI), glycated hemoglobinA1c (GHbA1c), fasting blood glucose (FBG), 2-hour postprandial blood glucose (2 h BG), total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), and risk of hypoglycemia (P ＜ 0.05), significantly increased high-density lipoprotein cholesterol (HDL-C) levels and risk of nausea (P ＜ 0.05). Subgroup analysis results showed that compared with the insulin monotherapy group, all combination groups exhibited lower GHbA1c levels (all P ＜ 0.05). Except for the GLP-1RA combined with aspart insulin group, all other combination groups had lower FBG levels (all P ＜ 0.01). Except for the GLP-1RA combined with aspart insulin + glargine insulin group, all other combination groups demonstrated lower 2 h BG levels (all P ＜ 0.01). Regarding blood lipids, compared with the insulin monotherapy group, except for the GLP-1RA combined with detemir insulin or aspart insulin + glargine insulin groups, all other combination groups showed lower TC levels (all P ＜ 0.01). Except for the GLP-1RA combined with regular insulin or aspart insulin + glargine insulin group, all other combination groups had lower TG levels (all P ＜ 0.05). Except for the GLP-1RA combined with aspart insulin group, all other combination groups exhibited lower LDL-C levels (all P ＜ 0.05). Except for the GLP-1RA combined with detemir insulin group, all other combination groups showed higher HDL-C levels (all P ＜ 0.01).
    Conclusion The combination of GLP-1RA and insulin significantly improves glycemic control, weight, and lipid profiles while reducing the risk of hypoglycemia in obese adults with T2DM. The efficacy is influenced by the type of insulin used in combination.

     

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