Table 2

Safety summary

CharacteristicDapagliflozin 5 mg + insulin (n = 271)Dapagliflozin 10 mg + insulin (n = 270)Placebo + insulin (n = 272)
AEs
 ≥1 AEs197 (72.7%)181 (67.0%)172 (63.2%)
 ≥1 AEs related to the study drug78 (28.8%)71 (26.3%)32 (11.8%)
 AE leading to study discontinuation17 (6.3%)12 (4.4%)11 (4.0%)
AEs of special interest
 Genital infection27 (10.0%)21 (7.8%)5 (1.8%)
 Urinary tract infection18 (6.6%)10 (3.7%)12 (4.4%)
 Renal impairment/failure2 (0.7%)00
 Fractures4 (1.5%)3 (1.1%)2 (0.7%)
 Hypotension/dehydration/hypovolemia8 (3.0%)2 (0.7%)2 (0.7%)
 Hypersensitivity18 (6.6%)10 (3.7%)17 (6.3)
 Cardiovascular events1 (0.4%)3 (1.1%)2 (0.7%)
SAEs
 ≥1 SAEs18 (6.6%)7 (2.6%)5 (1.8%)
 ≥1 SAEs related to the study drug13 (4.8%)3 (1.1%)2 (0.7%)
 SAEs leading to study discontinuation12 (4.4%)3 (1.1%)3 (1.1%)
 Death000
Hypoglycemia
 ≥1 SAE of hypoglycemia5 (1.8%)01 (0.4%)
 Hypoglycemia leading to study discontinuation2 (0.7%)00
Ketone-related events
 ≥1 ketone-related SAEs9 (3.3%)3 (1.1%)0
 Ketone-related SAE leading to study discontinuation8 (3.0%)2 (0.7%)0
Adjudicated definite DKA
 Number of patients with definite DKA7 (2.6%)6 (2.2%)0
 Number of events adjudicated as definite DKA7 (25.0%)6 (33.3%)0
 Incidence rate per 100 patient-years5.834.990
 Number of CSII users experiencing definite DKA6 (6.5%)3 (3.3%)0
 Male-to-female ratio in patients experiencing definite DKA2:51:50
 Severity of adjudicated DKA events
  Mild3 (42.9%)3 (50.0%)NA
  Moderate3 (42.9%)1 (16.7%)NA
  Severe1 (14.3%)2 (33.3%)NA
 Primary cause for adjudicated definite DKA events
  Insulin pump failure1 (14.3%)2 (33.3%)0
  Missed insulin dose2 (28.6%)1 (16.7%)0
  Not identified4 (57.1%)00
  Other03 (50.0%)*0
 Mean percent TDD (IU) reduction compared with baseline for week before DKA event−16.83−21.97NA
 Mean percent TDD (IU) reduction compared with baseline at the end of 24-week treatment period−15.68−22.93NA
Events adjudicated as not DKA
 Number of patients with event(s) adjudicated as possible DKA6 (2.2%)4 (1.5%)2 (0.7%)
 Number of events adjudicated as possible DKA7 (25.0%)4 (22.2%)2 (13.3%)
 Number of patients with event(s) adjudicated as unlikely DKA8 (3.0%)4 (1.5%)7 (2.6%)
 Number of events adjudicated as unlikely DKA14 (50.0%)8 (44.4%)13 (86.7%)
  • All data are n (%) unless otherwise indicated. The table includes non-SAEs with onset on or after the first date/time of double-blind treatment and on or prior to the last day of short-term double-blind treatment plus 4 days or up to the start date of the long-term period if earlier. The table includes SAEs with onset on or after the first date/time of double-blind treatment and on or prior to the last day of short-term double-blind treatment plus 30 days or up to the start date of the long-term period if earlier. Only hypoglycemia and DKA reported by the investigator as SAE are included in the AE, related AE, SAE, related SAE, and AE leading to discontinuation summary lines. All reported hypoglycemia events and events sent for DKA adjudication with onset within 4 days of last day of treatment are included in the hypoglycemia and events sent for DKA adjudication lines, respectively. NA, not applicable.

  • *Cause for DKA included alcohol intake, stress, and stroke.

  • †Means apply for patients with definite DKA.