The elevated risk of Parkinson’s disease in patients with diabetes might be mitigated depending on the type of drugs prescribed to treat diabetes. Population data for risk of Parkinson’s disease in users of the newer types of drugs used in diabetes are scarce. We compared the risk of Parkinson’s disease in patients with diabetes exposed to thiazolidinediones (glitazones), glucagon-like peptide-1 (GLP-1) receptor agonists and dipeptidyl peptidase 4 (DPP4) inhibitors, with the risk of Parkinson’s disease of users of any other oral glucose lowering drugs. A population-based, longitudinal, cohort study was conducted using historic primary care data from The Health Improvement Network. Patients with a diagnosis of diabetes and a minimum of two prescriptions for diabetes medications between January 2006 and January 2019 were included in our study. The primary outcome was the first recording of a diagnosis of Parkinson’s disease after the index date, identified from clinical records. We compared the risk of Parkinson’s disease in individuals treated with glitazones or DPP4 inhibitors and/or GLP-1 receptor agonists to individuals treated with other antidiabetic agents using a Cox regression with inverse probability of treatment weighting based on propensity scores. Results were analysed separately for insulin users. Among 100 288 patients [mean age 62.8 years (standard deviation 12.6)], 329 (0.3%) were diagnosed with Parkinson’s disease during the median follow-up of 3.33 years. The incidence of Parkinson’s disease was 8 per 10 000 person-years in 21 175 patients using glitazones, 5 per 10 000 person-years in 36 897 patients using DPP4 inhibitors and 4 per 10 000 person-years in 10 684 using GLP-1 mimetics, 6861 of whom were prescribed GTZ and/or DPP4 inhibitors prior to using GLP-1 mimetics. Compared with the incidence of Parkinson’s disease in the comparison group (10 per 10 000 person-years), adjusted results showed no evidence of any association between the use of glitazones and Parkinson’s disease [incidence rate ratio (IRR) 1.17; 95% confidence interval (CI) 0.76–1.63; P = 0.467], but there was strong evidence of an inverse association between use of DPP4 inhibitors and GLP-1 mimetics and the onset of Parkinson’s disease (IRR 0.64; 95% CI 0.43–0.88; P < 0.01 and IRR 0.38; 95% CI 0.17–0.60; P < 0.01, respectively). Results for insulin users were in the same direction, but the overall size of this group was small. The incidence of Parkinson’s disease in patients diagnosed with diabetes varies substantially depending on the treatment for diabetes received. The use of DPP4 inhibitors and/or GLP-1 mimetics is associated with a lower rate of Parkinson’s disease compared to the use of other oral antidiabetic drugs.

中文翻译：

---

糖尿病药物和帕金森氏病的风险：糖尿病患者的队列研究

糖尿病患者帕金森氏病的高风险可能会减轻，具体取决于治疗糖尿病的药物类型。缺乏用于糖尿病的新型药物使用者的帕金森氏病风险的人口数据很少。我们比较了暴露于噻唑烷二酮类药物（格列酮类），胰高血糖素样肽-1（GLP-1）受体激动剂和二肽基肽酶4（DPP4）抑制剂的糖尿病患者的帕金森氏病的风险与任何使用者的帕金森氏病的风险其他口服降糖药。使用来自健康改善网络的历史性初级保健数据进行了基于人群的纵向队列研究。我们的研究包括2006年1月至2019年1月之间诊断为糖尿病且至少有两种糖尿病药物处方的患者。主要结果是从临床记录中确定的索引日期后首次记录帕金森氏病的诊断。我们使用Cox回归比较了使用格列酮或DPP4抑制剂和/或GLP-1受体激动剂治疗的患者与使用其他抗糖尿病药治疗的患者发生帕金森氏病的风险，并根据倾向评分对治疗加权的概率与之相反。分别对胰岛素使用者的结果进行了分析。在100 288名患者中（平均年龄62.8岁（标准差12.6）），在中位随访期3.33年中，有329名（0.3％）被诊断出患有帕金森氏病。21 175名使用格列酮类药物的患者中，帕金森氏病的发病率为每10 000人年8，36 897例使用DPP4抑制剂的患者中，每10 000人年中有5例，使用GLP-1模拟物的患者中每10 684人中有10,000人年中的4人，其中有6861人在使用GLP-1模拟物之前已服用GTZ和/或DPP4抑制剂。与比较组中帕金森氏病的发生率（每10 000人年10例）相比，调整后的结果表明，没有使用格列酮类药物与帕金森氏病相关的证据[发生率比（IRR）1.17；95％置信区间（CI）0.76-1.63；P  =  0.467]，但有强有力的证据表明，使用DPP4抑制剂和GLP-1模拟物与帕金森氏病的发作呈负相关（IRR 0.64； 95％CI 0.43-0.88；P <  0.01和IRR 0.38； 95％ CI 0.17–0.60；P <  0.01）。胰岛素使用者的结果是相同的，但该组的总体规模很小。在诊断为糖尿病的患者中，帕金森氏病的发病率根据所接受的糖尿病治疗有很大不同。与使用其他口服降糖药相比，使用DPP4抑制剂和/或GLP-1模拟物可降低帕金森氏病的发病率。