Abou Elezz Amr M, Khalefa Kareem, Gadelmawla Ahmed Farid, Khattab Youssef A, Abo Zeid Mohamed
Faculty of Medicine, Tanta University, Tanta, Egypt.
Faculty of Medicine, Menoufia University, Menoufia, Egypt.
Inflammopharmacology. 2025 Aug 5. doi: 10.1007/s10787-025-01873-0.
Recent studies highlighted the relation between type 2 diabetes and Parkinson's disease, suggesting a relation between insulin resistance and α-synuclein aggregation. Antidiabetic medications, including GLP-1 receptor agonists and PPAR-γ agonists, have shown potential neuroprotective effects. We conducted a comprehensive literature search retrieving randomized controlled trials (RCTs) comparing antidiabetic drugs and placebo. Key outcomes included motor and non-motor symptoms, along with the safety profile. Data were analyzed using RevMan, and trial sequential analysis as well as sensitivity analysis were conducted to ensure the robustness of our results. In addition, to ensure the reliability of our evidence, we conducted the GRADE evaluation approach. Seven RCTs, with 973 patients, were eligible for our inclusion criteria. Antidiabetic drugs have shown no significant difference from placebo concerning change in MDS-UPDRS scores while on medication in Parts I, II, III, IV (MD = -0.04, 95% CI [-0.74 to 0.66], p = 0.90), (MD = -0.88, 95% CI [-2.11 to 0.34], p = 0.16), (MD = -1.10, 95% CI [-2.61 to 0.42], p = 0.16), (MD = -0.09, 95% CI [-0.45 to 0.27], p = 0.64), respectively. However, for MATTIS-DRS and MADRS scores, results showed a significant difference favoring GLP-1 agonists (MD = 2.42, 95% CI [0.01 to 4.83], p = 0.05), (MD = -2.08, 95% CI [-3.93 to -0.23], p = 0.03) respectively. As for safety profile, results revealed significant differences favoring the placebo group. This meta-analysis concludes that antidiabetic drugs in early-to mid-stage Parkinson's disease show no significant benefit considering non-motor symptoms detected by MDS-UPDRS I, with TSA confirming this finding as a conclusive result. Similarly, no notable effects on motor symptoms were observed, although future trials are needed. GLP-1 agonists revealed potential antidepressant effects as well as improving cognitive functions detected by MADRS and MATTIS-DRS, respectively. However, antidiabetic drugs were associated with higher risks of gastrointestinal adverse effects such as nausea, vomiting, and weight loss.
近期研究强调了2型糖尿病与帕金森病之间的关系，提示胰岛素抵抗与α-突触核蛋白聚集之间存在关联。包括胰高血糖素样肽-1（GLP-1）受体激动剂和过氧化物酶体增殖物激活受体-γ（PPAR-γ）激动剂在内的抗糖尿病药物已显示出潜在的神经保护作用。我们进行了全面的文献检索，检索比较抗糖尿病药物与安慰剂的随机对照试验（RCT）。主要结局包括运动和非运动症状以及安全性。使用RevMan分析数据，并进行试验序贯分析和敏感性分析以确保结果的稳健性。此外，为确保证据的可靠性，我们采用了GRADE评估方法。七项RCT（共973例患者）符合我们的纳入标准。在服用药物期间，抗糖尿病药物在统一帕金森病评定量表（MDS-UPDRS）第I、II、III、IV部分的得分变化方面与安慰剂相比无显著差异（平均差[MD]=-0.04，95%置信区间[CI][-0.74至0.66]，p=0.90），（MD=-0.88，95%CI[-2.11至0.34]，p=0.16），（MD=-1.10，95%CI[-2.61至0.42]，p=0.16），（MD=-0.09，95%CI[-0.45至0.27]，p=0.64）。然而，对于帕金森病综合评定量表（MATTIS-DRS）和蒙哥马利-艾森伯格抑郁量表（MADRS）得分，结果显示有利于GLP-1激动剂的显著差异（MD=2.42，95%CI[0.01至4.83]，p=0.05），（MD=-2.08，95%CI[-3.93至-0.23]，p=0.03）。至于安全性，结果显示有利于安慰剂组的显著差异。这项荟萃分析得出结论，考虑到MDS-UPDRS I检测到的非运动症状，抗糖尿病药物在帕金森病早期至中期没有显著益处，试验序贯分析证实这一发现为确定性结果。同样，未观察到对运动症状有显著影响，尽管未来仍需要进行试验。GLP-1激动剂分别显示出潜在的抗抑郁作用以及改善由MADRS和MATTIS-DRS检测到的认知功能。然而，抗糖尿病药物与更高的胃肠道不良反应风险相关，如恶心、呕吐和体重减轻。
