Dapagliflozin (DAPA), an SGLT2 inhibitor, lowers blood glucose by increasing renal glucose excretion. Data were pooled from the short-term double-blind periods of 12 placebo (PBO)-controlled trials (>4500 patients). Adverse events (AEs) were slightly more common with DAPA vs PBO; serious AEs and discontinuations due to AEs were balanced across groups. Hypoglycaemia was more common with DAPA vs PBO; in individual studies imbalances were only observed when DAPA was combined with sulphonylurea or insulin. Genital infections and UTI were more common with DAPA vs PBO with imbalances less marked for UTIs. Mean changes in systolic/diastolic blood pressure were -4.0/-2.0 vs -0.9/-0.5 mmHg for DAPA vs PBO without increases in measured orthostatic hypotension (3.9% vs 3.7% for DAPA vs PBO). AEs of volume depletion (hypotension/dehydration/hypovolaemia) were seen in 0.4% for PBO vs 0.6-1.2% for DAPA. AEs of renal impairment/failure were balanced across groups (0.9% for PBO vs 0.9-1.4% for DAPA). Minor changes in serum electrolytes were seen with DAPA, with small increases in serum Mg and P. To screen for rare events, all DAPA doses from 19 Phase 2b/3 trials were reviewed. Incident rates for malignancies were similar for DAPA (1.4%) vs control (1.3%); breast and bladder cancer events were more common with DAPA. Elevated liver laboratory tests were seen in 4.4% vs 4.2% for DAPA vs control. CV death, MI, stroke or hospitalisation for unstable angina were similar for DAPA vs control, (HR 0.82; 95% CI: 0.583, 1.152). Trends in CV events and specific malignancies will be further evaluated in a randomised CV outcomes trial and complementary observational studies.