Monotherapy with Metformin versus Sulfonylureas and Risk of Cancer in Type 2 Diabetic Patients: A Systematic Review and Meta-Analysis

Abstract EN

Background.

Accumulating evidence suggests that patients with type 2 diabetes mellitus and hyperinsulinemia are at an increased risk of developing malignancies.

It remains to be fully elucidated whether the use of metformin, an insulin sensitizer, and/or sulfonylureas, insulin secretagogues, affects cancer incidence in subjects with type 2 diabetes mellitus.

Objective.

A systematic review and meta-analysis was performed to compare the risk of cancer incidence associated with monotherapy with metformin compared with monotherapy with sulfonylureas in type 2 diabetes mellitus patients.

Methods.

Search was performed throughout MEDLINE/PubMed, EMBASE, Google Scholar, Cochrane Central Register of Controlled Trials (CENTRAL), and ClinicalTrials.gov up until December 2018.

In this meta-analysis, each raw data (unadjusted) and study-specific (adjusted) relative risks (RRs) was combined and the pooled unadjusted and adjusted RRs with the 95% CI were calculated using the random-effects model with inverse-variance weighting.

Heterogeneity among the studies was evaluated using I2 statistics.

Publication bias was evaluated using the funnel plot asymmetry test.

The Newcastle-Ottawa scale (NOS) was used to assess the study quality.

Results.

A total of 8 cohort studies were included in the meta-analysis.

Obvious heterogeneity was noted, and monotherapy with metformin was associated with a lower risk of cancer incidence (unadjusted RR=0.74, 95% CI: 0.55-0.99, I2=97.89%, p<0.00001; adjusted RR=0.76, 95% CI: 0.54–1.07, I2=98.12%, p<0.00001) compared with monotherapy with sulfonylurea, using the random-effects model with inverse-variance weighting.

Conclusions.

According to this review, the monotherapy with metformin appears to be associated with a lower risk of cancer incidence than monotherapy with sulfonylurea in patients with type 2 diabetes.

This analysis is mainly based on cohort studies, and our findings underscore the need for large-scale randomized controlled trials to establish the effect of metformin monotherapy, relative to sulfonylureas monotherapy on cancer.