Safety data were pooled from 12 randomized, placebo-controlled Phase 2b/3 trials to analyze the association of glucosuria with genital infection in patients with suboptimally controlled diabetes (HbA1c > 6.5 % -12 % ). Patients were randomized to receive dapagliflozin (2.5 mg, 5 mg, or 10 mg) or placebo once daily, either as monotherapy or add-on to metformin, insulin, sulfonylurea, or thiazolidinedione for 12-24 weeks. The incidence of clinical diagnoses and of events suggestive of genital infection was evaluated.
The pooled safety data included 4545 patients: 3152 who received once-daily dapagliflozin (2.5 mg [n = 814], 5 mg [n = 1145], or 10 mg [n = 1193]) as monotherapy or add-on treatment, and 1393 placebo-treated patients. For dapagliflozin 2.5 mg, 5 mg, 10 mg, and placebo, diagnosed infections were reported in 4.1 % , 5.7 % , 4.8 % , and 0.9 % , respectively. Most infections were mild or moderate and responded to standard antimicrobial treatment. Discontinuation due to these events was rare. No clear dose-response relationship between dapagliflozin and genital infection was demonstrated.
Treatment with dapagliflozin 2.5 mg, 5 mg, or 10 mg once daily is accompanied by an increased risk of vulvovaginitis or balanitis, related to the induction of glucosuria. Events were generally mild to moderate, clinically manageable, and rarely led to discontinuation of treatment.