Department of Basic and Clinical Sciences, University of Nicosia Medical School, Nicosia, Cyprus.
Andrology. 2023 Feb;11(2):245-256. doi: 10.1111/andr.13328. Epub 2022 Dec 9.
Phosphodiesterase 5 inhibitors (PDE5i), since their introduction in the late 1990s, have proven their efficacy in treating several conditions, predominantly pulmonary hypertension and erectile dysfunction where they remain the first-line therapeutic option. However, in the recent years, growing evidence from both animal and human studies has emerged to suggest the additional benefits of PDE5i in cardiovascular and metabolic disorders. This is of specific interest to the diabetes population where prevalent cardiovascular disease and metabolic dysregulation significantly contribute to the increased morbidity and mortality.
To examine the available data on the non-standard, pleiotropic effects of PDE5i in patients with diabetes mellitus.
The review of the published background research, preclinical studies and clinical trials.
In human studies, PDE5 inhibition appeared to be associated with reduced cardiovascular mortality and overall improved clinical outcomes in those with established cardiovascular disease. PDE5i were also consistently found to reduce albuminuria in subjects with diabetic nephropathy. Furthermore, animal data suggest a plausible effect of this group of medication on sensory function and neuropathic symptoms in diabetic neuropathy as well as improved wound healing. A decrease in insulin resistance and augmentation of beta cell function seen in preclinical studies has not been consistently demonstrated in human trials.
In animal models, PDE5 inhibition appears to decrease oxidative stress and reduce some of the micro- and macrovascular complications associated with diabetes. However, data from human trials are limited and largely inconsistent, highlighting the need for adequately powered, randomised-controlled trials in diabetic cohorts in order to fully assess the benefits of PDE5i in this group of patients.
自 20 世纪 90 年代末磷酸二酯酶 5 抑制剂（PDE5i）问世以来，已证明其在治疗多种疾病方面的疗效，主要是肺动脉高压和勃起功能障碍，在这些疾病中，它们仍然是首选的治疗方法。然而，近年来，来自动物和人类研究的越来越多的证据表明，PDE5i 在心血管和代谢紊乱方面具有额外的益处。这对糖尿病患者群体特别有意义，因为普遍存在的心血管疾病和代谢失调显著增加了发病率和死亡率。
检查现有关于糖尿病患者 PDE5i 非标准、多效性作用的可用数据。
对已发表的背景研究、临床前研究和临床试验进行综述。
在人类研究中，PDE5 抑制似乎与降低心血管死亡率和改善已确诊心血管疾病患者的总体临床结局有关。PDE5i 还被一致发现可降低糖尿病肾病患者的白蛋白尿。此外，动物数据表明，这组药物对糖尿病神经病变中的感觉功能和神经病变症状以及改善伤口愈合可能有一定的作用。在临床前研究中观察到的胰岛素抵抗降低和β细胞功能增强在人类试验中并未得到一致证实。
在动物模型中，PDE5 抑制似乎可降低氧化应激，并减少与糖尿病相关的一些微血管和大血管并发症。然而，来自人类试验的数据有限且不一致，突出表明需要在糖尿病患者队列中进行足够规模、随机对照试验，以充分评估 PDE5i 在这组患者中的获益。
