长效和短效磷酸二酯酶5抑制剂对糖化血红蛋白水平的影响：一项系统评价和荟萃分析。
Effect of long and short half-life PDE5 inhibitors on HbA1c levels: a systematic review and meta-analysis.
作者信息
Kim Joseph, Zhao Rui, Kleinberg Lawrence Richard, Kim Kitai
机构信息
Department of Biophysics, Johns Hopkins University, 3400 N Charles Street, Baltimore, MD, 21218, USA.
Department of Biochemistry and Molecular Genetics, University of Alabama Birmingham Heersink School of Medicine, Room 714, 1825 University Blvd., Birmingham, AL, 35294-2182, USA.
出版信息
EClinicalMedicine. 2024 Dec 31;80:103035. doi: 10.1016/j.eclinm.2024.103035. eCollection 2025 Feb.
BACKGROUND
Phosphodiesterase 5 (PDE5) inhibitors, owing to their mechanism of action, have been gaining recognition as a potential case of drug repurposing and combination therapy for diabetes treatment. We aimed to examine the effect of long and short half-life PDE5 inhibitors have on Haemoglobin A1c (HbA1c) levels.
METHODS
A systematic review and meta-analysis was conducted of randomised controlled trials (RCTs) in people with elevated HbA1c (>6%) to assess mean difference in HbA1c levels from baseline versus controls after any PDE5 inhibitor intervention of ≥4 weeks, excluding multiple interventions. Cochrane CENTRAL, PMC Medline, ClinicalTrials.gov, and WHO ICTRP were searched without language restrictions up to September 30, 2024. Summary data from published data were extracted. PRISMA and Cochrane guidelines used to extract and assess data using a random-effects meta-analysis. This study is registered with the Research Registry, reviewregistry1733.
FINDINGS
Among 1096 studies identified, in analysis of 13 studies with 1083 baseline patients, long half-life PDE5 inhibitors (tadalafil, PF-00489791) had decreases in HbA1c while short half-life PDE5 inhibitors (sildenafil, avanafil) had no change. Five (38.5%) studies had a low risk of bias, and eight (61.5%) had some concerns. Long half-life inhibitors had significant mean decrease of -0.40% ([-0.66, -0.14], p = 0.002, I = 82%, 7.70% baseline HbA1c). Short half-life inhibitors had insignificant mean difference of +0.08% ([-0.16, 0.33], p = 0.51, I = 40%, 7.73% baseline HbA1c). In ≥8-week trials with participants with type 2 diabetes (T2D) and mean HbA1c ≥ 6.5%, long half-life inhibitors had significant mean decrease of -0.50% ([-0.83, -0.17], I = 88%, p = 0.003); short half-life inhibitors had significant mean increase of +0.36% ([0.03, 0.68], I = 3%, p = 0.03).
INTERPRETATION
At the well-controlled HbA1c of the participants, previous literature shows current diabetes treatments have similar HbA1c decreases, so the HbA1c mean difference of long half-life PDE5 inhibitors may indeed be clinically relevant. This suggests future investigation into PDE5 inhibitors as part of combination therapy or as therapy for high HbA1c individuals is needed, especially because of variable risk of biases, homogeneity, and sample sizes in our study.
FUNDING
None.
背景
磷酸二酯酶5（PDE5）抑制剂因其作用机制，已逐渐被认可为一种具有药物重新利用和联合治疗糖尿病潜力的药物。我们旨在研究长半衰期和短半衰期PDE5抑制剂对糖化血红蛋白（HbA1c）水平的影响。
方法
对糖化血红蛋白水平升高（>6%）的人群进行的随机对照试验（RCT）进行系统评价和荟萃分析，以评估在任何PDE5抑制剂干预≥4周后（不包括多种干预措施），HbA1c水平相对于基线与对照组的平均差异。检索Cochrane CENTRAL、PMC Medline、ClinicalTrials.gov和WHO ICTRP，检索截至2024年9月30日，无语言限制。从已发表的数据中提取汇总数据。使用PRISMA和Cochrane指南，通过随机效应荟萃分析来提取和评估数据。本研究已在Research Registry注册，注册号为reviewregistry1733。
结果
在识别出的1096项研究中，对13项研究（1083名基线患者）进行分析，长半衰期PDE5抑制剂（他达拉非、PF - 00489791）可降低HbA1c水平，而短半衰期PDE5抑制剂（西地那非、阿伐那非）则无变化。5项（38.5%）研究存在低偏倚风险，8项（61.5%）研究存在一些问题。长半衰期抑制剂的平均降低幅度显著，为-0.40%（[-0.66, -0.14]，p = 0.002，I² = 82%，基线HbA1c为7.70%）。短半衰期抑制剂的平均差异不显著，为+0.08%（[-0.16, 0.33]，p = 0.51，I² = 40%，基线HbA1c为7.73%）。在≥8周的试验中，对于2型糖尿病（T2D）患者且平均HbA1c≥6.5%，长半衰期抑制剂的平均降低幅度显著，为-0.50%（[-0.83, -0.17]，I² = 88%，p = 0.003）；短半衰期抑制剂的平均升高幅度显著，为+0.36%（[0.03, 0.68]，I² = 3%，p = 0.03）。
解读
在参与者HbA1c得到良好控制的情况下，既往文献表明目前的糖尿病治疗方法使HbA1c降低程度相似，因此长半衰期PDE5抑制剂的HbA1c平均差异可能确实具有临床意义。这表明未来需要对PDE5抑制剂作为联合治疗的一部分或作为高HbA1c个体的治疗方法进行研究，特别是考虑到我们研究中存在的偏倚风险、同质性和样本量的差异。
资金来源
无。
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