Safety summary
| Characteristic | Dapagliflozin 5 mg + insulin (n = 271) | Dapagliflozin 10 mg + insulin (n = 270) | Placebo + insulin (n = 272) |
|---|---|---|---|
| AEs | |||
| ≥1 AEs | 197 (72.7%) | 181 (67.0%) | 172 (63.2%) |
| ≥1 AEs related to the study drug | 78 (28.8%) | 71 (26.3%) | 32 (11.8%) |
| AE leading to study discontinuation | 17 (6.3%) | 12 (4.4%) | 11 (4.0%) |
| AEs of special interest | |||
| Genital infection | 27 (10.0%) | 21 (7.8%) | 5 (1.8%) |
| Urinary tract infection | 18 (6.6%) | 10 (3.7%) | 12 (4.4%) |
| Renal impairment/failure | 2 (0.7%) | 0 | 0 |
| Fractures | 4 (1.5%) | 3 (1.1%) | 2 (0.7%) |
| Hypotension/dehydration/hypovolemia | 8 (3.0%) | 2 (0.7%) | 2 (0.7%) |
| Hypersensitivity | 18 (6.6%) | 10 (3.7%) | 17 (6.3) |
| Cardiovascular events | 1 (0.4%) | 3 (1.1%) | 2 (0.7%) |
| SAEs | |||
| ≥1 SAEs | 18 (6.6%) | 7 (2.6%) | 5 (1.8%) |
| ≥1 SAEs related to the study drug | 13 (4.8%) | 3 (1.1%) | 2 (0.7%) |
| SAEs leading to study discontinuation | 12 (4.4%) | 3 (1.1%) | 3 (1.1%) |
| Death | 0 | 0 | 0 |
| Hypoglycemia | |||
| ≥1 SAE of hypoglycemia | 5 (1.8%) | 0 | 1 (0.4%) |
| Hypoglycemia leading to study discontinuation | 2 (0.7%) | 0 | 0 |
| Ketone-related events | |||
| ≥1 ketone-related SAEs | 9 (3.3%) | 3 (1.1%) | 0 |
| Ketone-related SAE leading to study discontinuation | 8 (3.0%) | 2 (0.7%) | 0 |
| Adjudicated definite DKA | |||
| Number of patients with definite DKA | 7 (2.6%) | 6 (2.2%) | 0 |
| Number of events adjudicated as definite DKA | 7 (25.0%) | 6 (33.3%) | 0 |
| Incidence rate per 100 patient-years | 5.83 | 4.99 | 0 |
| Number of CSII users experiencing definite DKA | 6 (6.5%) | 3 (3.3%) | 0 |
| Male-to-female ratio in patients experiencing definite DKA | 2:5 | 1:5 | 0 |
| Severity of adjudicated DKA events | |||
| Mild | 3 (42.9%) | 3 (50.0%) | NA |
| Moderate | 3 (42.9%) | 1 (16.7%) | NA |
| Severe | 1 (14.3%) | 2 (33.3%) | NA |
| Primary cause for adjudicated definite DKA events | |||
| Insulin pump failure | 1 (14.3%) | 2 (33.3%) | 0 |
| Missed insulin dose | 2 (28.6%) | 1 (16.7%) | 0 |
| Not identified | 4 (57.1%) | 0 | 0 |
| Other | 0 | 3 (50.0%)* | 0 |
| Mean percent TDD (IU) reduction compared with baseline for week before DKA event† | −16.83 | −21.97 | NA |
| Mean percent TDD (IU) reduction compared with baseline at the end of 24-week treatment period† | −15.68 | −22.93 | NA |
| Events adjudicated as not DKA | |||
| Number of patients with event(s) adjudicated as possible DKA | 6 (2.2%) | 4 (1.5%) | 2 (0.7%) |
| Number of events adjudicated as possible DKA | 7 (25.0%) | 4 (22.2%) | 2 (13.3%) |
| Number of patients with event(s) adjudicated as unlikely DKA | 8 (3.0%) | 4 (1.5%) | 7 (2.6%) |
| Number of events adjudicated as unlikely DKA | 14 (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.