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SGLT2 Inhibitors and Stroke Risk in Patients with Type 2 Diabetes—A Systematic Review and Meta-analysis

Aims: SGLT2 inhibitors are a novel drug used to treat diabetes. They also have positive cardiovascular benefits. However, there is some debate regarding possible effects of SGLT2 inhibitors on stroke risk. Here, we conduct a meta-analysis of relevant RCTs to evaluate the effects of SGLT2 inhibitors on stroke risk with T2DM. Materials and Methods: We searched Pubmed, Embase, CENTRAL and ClinicalTrials.gov from database inception up to September 19, 2017. We included RCTs that enrolled patients with T2DM, compared SGLT2 inhibitors vs. placebo or other comparators for at least 24 weeks, and reported the observed effects of SGLT2 inhibitors on stroke events. Subgroup analyses were performed for gender, age, duration of diabetes, race, BMI, and HbA1C levels. A random-effects meta-analysis was performed to calculate the RR with 95% CI. Results: We identified 32 eligible trials enrolling 75,540 participants that compared three SGLT2 inhibitors (canagliflozin, dapagliflozin, and empagliflozin) to placebo and other active antidiabetic treatments. The incidence of stroke in groups with SGLT2 inhibitor monotherapy or combination therapy was not significantly different from that in control groups, with RR=1.01 (95% CI 0.93-1.10, p =0.972) and RR=1.0 (95% CI 0.92-1.09, p =0.846), respectively. There were no significant differences in RRs between three SGLT2 inhibitors; canagliflozin, RR=0.91; dapagliflozin, RR=0.99; and empagliflozin, RR=1.03. Subgroup analyses showed that the RR values were not affected by gender, age, duration of diabetes, BMI, and HbA1C levels; however, there was a small racial disparity, with black participants having a lower incidence of stroke than white or Asian participants. Conclusions: SGLT2 inhibitor therapy does not increase stroke incidence, and no significant differences in the RR for stroke were observed among three SGLT2 inhibitors (class effect). However, black patients did have a lower stroke incidence than white or Asian patients. Disclosure M. Guo: None. Y. Xu: None.