Dipeptidyl peptidase 4-inhibitor treatment was associated with a reduced incidence of neoplasm in patients with type 2 diabetes: a meta-analysis of 115 randomized controlled trials with 121961 participants

To evaluate the association between dipeptidyl peptidase 4 inhibitor (DPP-4i) and the incidence of neoplasm in patients with type 2 diabetes (T2D). Pubmed, Medline, Embase, the Cochrane Central Register of Controlled Trials and Clinicaltrial.gov website were searched from May 2002 to December 2021. Randomized controlled trials with reports of neoplasm events which compared DPP-4i versus non-DPP-4i users. Generally, DPP-4i was associated with a decreased incidence of overall neoplasm events in patients with T2D when compared with non-DPP-4i agents (OR = 0.91, 95%CI, 0.8 to 0.97). Moreover, the incidence of rectal neoplasm, especially rectal malignant neoplasm, and the incidence of skin neoplasm were significantly decreased in DPP-4i users. The overall neoplasm events were less frequent in DPP-4i users who were elderly, or male, or obese, or Caucasian, or with over 10 years of diabetes, or with follow-up duration over 52 weeks. DPP-4i was associated with decreased risks of overall neoplasm, rectal neoplasm, rectal malignant neoplasm and skin neoplasm in patients with T2D. The overall neoplasm events were less frequent in patient with DPP-4i treatment who were elderly, male, obese, Caucasian, with long diabetes durations and with long follow-up durations. Further investigations are still required. CRD42021273627.

本研究旨在评估二肽基肽酶4抑制剂（dipeptidyl peptidase 4 inhibitor, DPP-4i）与2型糖尿病（type 2 diabetes, T2D）患者肿瘤发生的关联。研究检索了2002年5月至2021年12月期间PubMed、Medline、Embase、考克兰对照试验中心注册库（Cochrane Central Register of Controlled Trials）及ClinicalTrials.gov网站的相关文献。纳入对比DPP-4i与非DPP-4i使用者、且报告了肿瘤事件的随机对照试验（randomized controlled trial）。
总体而言，与非DPP-4i类药物相比，二肽基肽酶4抑制剂与2型糖尿病患者的总体肿瘤事件发生率降低相关（比值比OR=0.91，95%置信区间95%CI：0.8~0.97）。此外，DPP-4i使用者的直肠肿瘤（尤其是直肠恶性肿瘤）及皮肤肿瘤发生率显著降低。在老年、男性、肥胖、高加索裔、糖尿病病程超过10年或随访时长超过52周的2型糖尿病患者中，DPP-4i使用者的总体肿瘤事件发生频率更低。
本研究结果显示，二肽基肽酶4抑制剂与2型糖尿病患者的总体肿瘤、直肠肿瘤、直肠恶性肿瘤及皮肤肿瘤风险降低相关；在老年、男性、肥胖、高加索裔、糖尿病病程较长及随访时长较长的接受DPP-4i治疗的患者中，总体肿瘤事件发生频率更低。仍需开展进一步研究。本研究注册编号：CRD42021273627。