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

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.

Results

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.

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 are still required.

Meta-analysis registration

CRD42021273627.

KEYWORDS:

• Dipeptidyl peptidase 4 inhibitor
• neoplasm
• cancer
• type 2 diabetes

Article highlights

• Existing research indicates inconsistent evidence on DPP-4is’ effects on neoplasm, with reports of elevated incidence of pancreas neoplasm, and reduced incidence of colorectal and breast neoplasm. Previous meta-analyses on DPP-4is and neoplasm did not conduct comprehensive sensitivity analyses in terms of tumor sites, tumor nature (malignant or benign) and other associated factors such as baseline characteristics of patients.

• DPP-4i treatment was found to be associated with a significant reduced incidence of overall neoplasm, skin neoplasm, and rectal neoplasm, especially rectal malignant neoplasm.

• Patients who were elderly, male, obese, Caucasian, with long diabetes durations, and with long follow-up durations were more likely to benefit from DPP-4i treatment with respect to reducing overall neoplasm incidence.

• DPP-4is might serve as a promising option for the management of diabetic patients with high risks of neoplasm.

Declaration of interest

LJ has received fees for lecture presentations and for consulting from AstraZeneca, Merck, Metabasis, MSD, Novartis, Eli Lilly, Roche, Sanofi-Aventis and Takeda. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Author contributions

LJ and XC conceptualized this study and designed the systematic review protocol; ZL, CL and JZ performed the study selection and data extraction; ZL and CL performed the statistical analyses; ZL, CL and XC prepared the outlines and wrote the manuscript. All authors contributed to the critical revision of manuscript drafts.

Data availability statement

All data relevant to the study are included in the article or uploaded as supplementary information. No more additional data are available.

Supplementary material

Supplemental data for this article can be accessed here

Additional information

Funding

This work was supported by National Natural Science Foundation of China (No.81970698 and No. 81970708) and Beijing Natural Science Foundation (No.7202216). The funding agencies had no roles in the study design, data collection or analysis, decision to publish or preparation of the manuscript.