Cancer risk of sulfonylureas in patients with type 2 diabetes mellitus: A systematic review

Background: Increasing evidence suggests that oral hypoglycemic agents used in type 2 diabetes mellitus (T2DM) may affect cancer risk. Sulfonylureas (SUs) are the most frequently used antidiabetic medications for T2DM. Whether using SUs has any effect on cancer has received considerable attention. The aim of this study was to assess the effects of SUs on cancer risk in T2DM patients.

Methods: Published studies were identified in PubMed, EMBASE, and the Cochrane Register of Clinical Studies, and ClinicalTrials.gov was searched for additional information to identify randomized controlled trials (RCTs), cohort studies, and case-control studies. The abstracts and full text were screened, data collected, and the risk of bias assessed for each individual study.

Results: Seventy-seven studies (33 RCTs, 27 cohort studies, and 17 case-control studies) were analyzed. The RCTs did not report a difference in the risk of malignant tumor between SU-treated T2DM patients and controls (odds ratio [OR] 0.96; 95% confidence interval [CI] 0.78-1.18); cohort studies showed that cancer risk was higher in patients using SUs than metformin (relative risk 1.60 [95%CI 1.37-1.87]; adjusted hazard ratio 1.13 [95%CI 1.06-1.19]), and case-control studies suggested a trend for increased cancer risk in those using SUs compared with non-SU users (adjusted OR 1.13; 95%CI 0.93-1.37).

Conclusions: The available evidence clearly shows that SUs can significantly increase the risk of cancer compared with metformin. Although the evidence suggests the possibility that SU users may have a higher risk of cancer than those using alternative medications in addition to metformin, it remains inadequate to enable definitive conclusions to be drawn.