Wu Dong, Wang Xiaowu, Liu Qiao, Luo Xia
Department of Pharmacy, Fuyang People's Hospital, Fuyang, Anhui, China.
Department of Clinical Laboratory, The Second People's Hospital of Fuyang, Fuyang Infection Disease Clinical College of Anhui Medical University, Fuyang, Anhui, China.
Diabetes Obes Metab. 2025 Aug;27(8):4354-4370. doi: 10.1111/dom.16474. Epub 2025 May 23.
To evaluate the efficacy and safety of oral hypoglycaemic drugs (OHDs) as an adjunct to insulin therapy in patients with type 1 diabetes mellitus (T1DM), addressing the need for optimized glycaemic control and reduced insulin dependency.
A systematic literature search was conducted across PubMed, Embase and the Cochrane Library to identify randomized clinical trials (RCTs) published up to October 31, 2024. Primary outcomes included changes in glycated haemoglobin (HbA1c) and hypoglycaemia risk. Secondary endpoints assessed six efficacy and seven safety measures using meta-analysis. Treatment effects were quantified using weighted mean difference (WMD) and risk ratios (RRs) with 95% confidence intervals (CIs). Subgroup and indirect comparisons were performed to explore variations across patient demographics and drug classes.
The meta-analysis included 51 RCTs with 8664 participants. Overall, compared with placebo, OHDs demonstrated significant reductions in HbA1c (WMD -0.32%, p < 0.001), fasting plasma glucose (WMD -0.91 mmol/L, p < 0.001), postprandial plasma glucose (WMD -2.08 mmol/L, p < 0.001), daily insulin dosage(WMD -4.88 IU/day, p < 0.001) and body weight (WMD -1.89 kg, p < 0.001), while improving the percentage time in the target glucose range of 3.9-10.0 mmol/L (WMD 6.04%, p = 0.04). However, no significant change was observed in BMI (WMD -0.18 kg/m, p = 0.08). Compared with placebo, OHDs did not increase the risk of hypoglycaemia (RR 1.01, p = 0.08), severe hypoglycaemia (RR 0.95, p = 0.73) or nocturnal hypoglycaemia (RR 0.97, p = 0.24), but were associated with elevated risks of serious adverse events (RR 1.30, p = 0.005), discontinuation due to adverse events (RR 1.88, p < 0.001), genital tract infection (RR 3.30, p < 0.001), gastrointestinal side effects (RR 1.98, p < 0.001) and ketoacidosis (RR 3.14, p < 0.001). Indirect comparisons favoured alpha glucosidase inhibitor (AGI) over thiazolidinediones for HbA1c reduction (mean difference -0.46%, p < 0.001). Subgroup analysis revealed greater fasting glucose reduction in adults compared to children/adolescents (WMD -1.15 mmol/L vs. -0.26 mmol/L, p of group difference = 0.02).
OHDs as adjunctive therapy in T1DM significantly improve glycaemic control and reduce insulin requirements. However, their use is associated with notable safety concerns, particularly ketoacidosis and other adverse events. Clinicians must conduct thorough risk assessments and tailor treatment plans to individual patient profiles to balance efficacy and safety. Future research should focus on long-term outcomes and strategies to mitigate adverse effects.
评估口服降糖药（OHDs）作为1型糖尿病（T1DM）患者胰岛素治疗辅助药物的疗效和安全性，以满足优化血糖控制和降低胰岛素依赖的需求。
在PubMed、Embase和Cochrane图书馆进行系统文献检索，以识别截至2024年10月31日发表的随机临床试验（RCT）。主要结局包括糖化血红蛋白（HbA1c）的变化和低血糖风险。次要终点使用荟萃分析评估六项疗效和七项安全指标。使用加权平均差（WMD）和风险比（RRs）及95%置信区间（CIs）对治疗效果进行量化。进行亚组和间接比较以探讨不同患者人口统计学特征和药物类别之间的差异。
荟萃分析纳入了51项RCT，共8664名参与者。总体而言，与安慰剂相比，OHDs在降低HbA1c（WMD -0.32%，p < 0.001）、空腹血糖（WMD -0.91 mmol/L，p < 0.001）、餐后血糖（WMD -2.08 mmol/L，p < 0.001）、每日胰岛素剂量（WMD -4.88 IU/天，p < 0.001）和体重（WMD -1.89 kg，p < 0.001）方面有显著降低，同时改善了血糖在3.9 - 10.0 mmol/L目标范围内的时间百分比（WMD 6.04%，p = 0.04）。然而，未观察到BMI有显著变化（WMD -0.18 kg/m²，p = 0.08）。与安慰剂相比，OHDs不会增加低血糖（RR 1.01，p = 0.08）、严重低血糖（RR 0.95，p = 0.73）或夜间低血糖（RR 0.97，p = 0.24）的风险，但与严重不良事件（RR 1.30，p = 0.005）、因不良事件停药（RR 1.88，p < 0.001）、生殖道感染（RR 3.30 p < 0.001）、胃肠道副作用（RR 1.98，p < 0.001）和酮症酸中毒（RR 3.14，p < 0.001）的风险升高有关。间接比较显示，在降低HbA1c方面，α-葡萄糖苷酶抑制剂（AGI）优于噻唑烷二酮类药物（平均差异 -0.46%，p < 0.001）。亚组分析显示，与儿童/青少年相比，成人空腹血糖降低幅度更大（WMD -1.15 mmol/L对 -0.26 mmol/L，组间差异p = z0.02）。
OHDs作为T1DM的辅助治疗可显著改善血糖控制并减少胰岛素需求。然而，其使用存在明显的安全问题，尤其是酮症酸中毒和其他不良事件。临床医生必须进行全面的风险评估，并根据个体患者情况制定治疗方案，以平衡疗效和安全性。未来的研究应关注长期结局和减轻不良反应的策略。
