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

Abstract

Objective : To evaluate the association between dipeptidyl peptidase 4 inhibitor (DPP-4i) and the incidence of neoplasm in patients with type 2 diabetes (T2D). Methods : We conducted a meta-analysis of randomized controlled trials (RCTs), using the data sources Pubmed, Medline, Embase, the Cochrane Central Register of Controlled Trials and Clinicaltrial.gov website from May 2002 to December 2021. RCTs with reports of neoplasm events which compared DPP-4i with non-DPP-4i active agents or placebo in patients with T2D were included. Two investigators independently screened eligible researches, extracted data, and assessed risk of bias with the Cochrane risk of bias tool. The primary endpoint of the meta-analysis was the association between DPP-4i and the incidence of overall neoplasm events (a composite endpoint of benign, malignant and undefined neoplasm) in patient with T2D. The incidence of benign or malignant neoplasm in DPP-4i users was regarded as the secondary endpoint while the incidence of site-specific neoplasm in DPP-4i users was interpreted as exploratory endpoints. Results : A total of 115 RCTs with 121961 participants were included. Generally, DPP-4i was associated with a decreased incidence of overall neoplasm events in patients with T2D when compared with other hypoglycemic agents or placebo (OR = 0.91, 95%CI, 0.8 to 0.97, I2 = 0%). Moreover, the incidence of rectal neoplasm (OR = 0.58, 95%CI, 0.37 to 0.93, I2 = 0%), especially rectal malignant neoplasm (OR = 0.59, 95%CI, 0.36 to 0.94, I2 = 0%), and the incidence of skin neoplasm (OR = 0.85, 95%CI, 0.72 to 0.99, I2 = 0%) were significantly decreased in DPP-4i users. Subgroup analyses indicated that the overall neoplasm events were less frequent in DPP-4i users who were elderly (age≥65 years old, OR = 0.88, 95%CI, 0.80 to 0.96, I2 = 0%), or male (OR = 0.89, 95%CI, 0.83 to 0.96, I2 = 0%), or obese (BMI≥30 kg/m2, OR = 0.93, 95%CI, 0.86 to 0.99, I2 = 0%), or Caucasian (OR = 0.91, 95%CI, 0.85 to 0.98, I2 = 0%), or with over 10 years of diabetes (OR = 0.87, 95%CI, 0.80 to 0.95, I2 = 0%), or with follow-up duration over 52 weeks (OR = 0.90, 95%CI, 0.84 to 0.96, I2 = 0%). Conclusions : 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 on the mechanisms of DPP-4i’s potential anti-tumor effects are still required. Meta-analysis registration : CRD42021273627.