Dipeptidyl peptidase-4 inhibitors and cancer risk in patients with type 2 diabetes: a meta-analysis of randomized clinical trials

Abstract

Some recent studies have suggested that the use of dipeptidyl peptidase-4 inhibitors (DPP4i) is associated with cancer development. However, some other studies suggest no such association. The aim of the present study was to evaluate the effect of DPP4i on the risk of developing cancers. The electronic databases PubMed, Medline, EMBASE, Web of Science and Cochrane Library and the clinical trial registry were searched for published and unpublished randomized clinical trials on humans. Eligible studies were RCTs conducted in patients with type 2 diabetes mellitus, comparing DPP4i with a placebo or other active drugs. A total of 72 trials with 35,768 and 33,319 patients enrolled for DPP4i and the comparison drugs, respectively. Overall, no significant associations were detected between the use of DPP4i and cancer development, in comparison with the use of other active drugs or placebo. The results were consistent across pre-defined subgroups stratified by type of DPP4i, type of cancer, drug for comparison, trial duration, or baseline characteristics. The results of this meta-analysis suggest that patients with type 2 diabetes treated with DPP4i do not have a higher risk of developing cancers than patients treated with a placebo or other drugs.

Dipeptidyl peptidase-4 inhibitors and the risks of autoimmune diseases in type 2 diabetes mellitus patients in Taiwan: a nationwide population-based cohort study

“…Since the first DPP-4 inhibitor sitagliptin (trade name, Januvia) was approved by the U.S. FDA in 2006, more than one hundred meta-analyses have focused on the efficacy and safety of DPP-4-inhibitors [41][42][43][44][45][46]. Nevertheless, whether or not DPP-4 inhibitors will influence the T cell immune homeostasis or in turn decrease the risk of autoimmune disease in human has not reached a consensus.…”

Dipeptidyl peptidase 4 inhibitors and their potential immune modulatory functions

“…All these trials demonstrate that gliptins do not increase tumor risk in T2DM patients. Zhao performed a meta-analysis with a total of 72 trials enrolled and no significant associations are detected between the use of gliptins and cancer development (Zhao et al, 2017), indicating the safety rather than benefits of gliptins in tumor.…”

Does the use of incretin‐based medications increase the risk of cancer in patients with type‐2 diabetes mellitus?

“…Further, in a pooled analysis of data from 25 clinical trials on 14 611 diabetes patients randomized to use either sitagliptin (a DPP‐4 inhibitor) or a control treatment (placebo, metformin, pioglitazone, a sulfonylurea medication, insulin, or metformin with rosiglitazone or pioglitazone) for between 12 weeks and 2 years, similar incidence rates of overall cancer in the two groups were observed (rate difference: −0.05 events per 100 person‐years (95% CI: −0.41, 0.30)) . Finally, authors of a recent meta‐analysis of results from a total of 72 RCTs on DPP‐4 inhibitors reported that the estimated risk ratio for overall cancer was 1.01 (95% CI: 0.91, 1.28) when the control treatment included the use of placebo, sulfonylureas, or metformin, while when the analysis was restricted to studies with sulfonylureas as the control treatment, the corresponding result was 1.40 (95% CI: 0.99, 1.96) …”

“…31 Finally, authors of a recent meta-analysis of results from a total of 72 RCTs on DPP-4 inhibitors reported that the estimated risk ratio for overall cancer was 1.01 (95% CI: 0.91, 1.28) when the control treatment included the use of placebo, sulfonylureas, or metformin, while when the analysis was restricted to studies with sulfonylureas as the control treatment, the corresponding result was 1.40 (95% CI: 0.99, 1.96). 32 In our primary analyses, we presumed the "class effect" of incretin-based medications on the risk of cancer. This presumption is supported by the fact that DPP-4 inhibitors and GLP-1 receptor agonists share at least some pathways potentially underlying these medications' hypothesized effect on cancer risk, 33 but it also seems to be supported by results from a CPRD-based study by Hicks et al, who…”