Sodium‐glucose co‐transporter‐2 (SGLT‐2) inhibitors and cancer: A meta‐analysis of randomized controlled trials

Abstract Aim The aim of this meta‐analysis of randomized trials was to assess the effects of SGLT‐2i on the overall incidence of malignancies and on different types of cancer, summerizing the results of trials with a duration of at least 1 year. This was done in light of the effect of SGLT‐2 inhibitors (SGLT‐2is) that has been highlighted by some studies, showing an increased incidence of bladder cancer, particularly with use of empagliflozin. Materials and methods A Medline and Embase search for “Canaglifozin”, “Dapaglifozin”, “Empaglifozin”, “Ertuglifozin”, “Ipraglifozin”, Tofoglifozin” or “Luseoglifozin” was performed, identifying randomized trials with a duration of more than 52 weeks up to 1 December 2018 that compared SGLT‐2is with placebo or active comparators. The outcomes considered were all types of cancer and several site‐specific cancers (ie, breast, pulmonary, gastrointestinal, hepatic, pancreatic, skin, prostate and bladder). Mantel–Haenszel odds ratios with 95% Confidence Intervals (MH‐OR, 95% CI) were calculated for all outcomes. Results A total of 27 trials fulfilled the inclusion criteria. Retrieved trials had enrolled 27 744 and 20 441 patients in SGLT‐2 inhibitor and comparator groups, respectively. No difference was observed in the incidence of all malignancies between patients allocated to SGLT‐2i and comparators (MH‐OR 0.98[0.77–1.24]). The incidence of bladder cancer, and of any other type of cancer, was not significantly increased by treatment with any SGLT‐2i. Conclusions Available data from randomized trials do not suggest a detrimental effect of SGLT‐2is on the incidence of malignancies in general, or in bladder cancer in particular.