Summary of adverse events and events of special interest, overall treatment period (baseline to 52 weeks)
| Placebo (n = 268) | Sotagliflozin 200 mg (n = 263) | Sotagliflozin 400 mg (n = 262) | |
|---|---|---|---|
| Any adverse event | 216 (80.6) | 215 (81.7) | 209 (79.8) |
| Serious adverse event | 20 (7.5) | 27 (10.3) | 29 (11.1) |
| Severe adverse event | 7 (2.6) | 12 (4.6) | 12 (4.6) |
| Death | 1 (0.4)* | 0 | 0 |
| Positively adjudicated adverse events | |||
| ≥1 severe hypoglycemia event† | 26 (9.7) | 17 (6.5) | 17 (6.5) |
| ≥1 severe nocturnal hypoglycemia event†** | 10 (3.7) | 10 (3.8) | 2 (0.8) |
| ≥1 DKA event | 1 (0.4) | 9 (3.4) | 11 (4.2) |
| ≥1 DKA event among CSII users | 1/160 (0.6) | 8/156 (5.1) | 7/157 (4.5) |
| ≥1 DKA event among MDI users | 0/108 | 1/107 (0.9) | 4/105 (3.8) |
| Major adverse cardiovascular events | |||
| Myocardial infarction or hospitalization for unstable angina | 3 (1.1) | 4 (1.5) | 0 |
| Stroke | 1 (0.4) | 0 | 1 (0.4) |
| Heart failure hospitalization | 0 | 0 | 0 |
| Coronary revascularization | 2 (0.7) | 2 (0.8) | 0 |
| Drug-induced liver injury | 0 | 0 | 2 (0.8) |
| Events of special interest | |||
| Any | 266 (99.3) | 260 (98.9) | 259 (98.9) |
| Genital mycotic infection | 9 (3.4) | 24 (9.1) | 34 (13.0) |
| Diarrhea‡ | 18 (6.7) | 22 (8.4) | 27 (10.3) |
| Urinary tract infection | 19 (7.1) | 26 (9.9) | 11 (4.2) |
| Bone fracture | 10 (3.7) | 9 (3.4) | 5 (1.9) |
| Renal event§ | 5 (1.9) | 7 (2.7) | 4 (1.5) |
| Volume depletion|| | 4 (1.5) | 8 (3.0) | 4 (1.5) |
| Malignancies of special interest¶ | 0 | 2 (0.8) | 2 (0.8) |
| Amputation | 0 | 0 | 1 (0.4) |
| Pancreatitis | 0 | 0 | 0 |
| Venous thrombotic event | 0 | 0 | 0 |
| Any documented hypoglycemia# (SMBG ≤3.9 mmol/L [≤70 mg/dL]) | 266 (99.3) | 260 (98.9) | 258 (98.5) |
| Any nocturnal documented hypoglycemia** | 247 (92.2) | 239 (90.9) | 238 (90.8) |
| Any SMBG value ≤3.0 mmol/L (≤55 mg/dL) | 248 (92.5) | 250 (95.1) | 244 (93.1) |
| Any adverse event leading to discontinuation | 11 (4.1) | 13 (4.9) | 17 (6.5) |
| Any event of special interest leading to discontinuation†† | 7 (2.6) | 8 (3.0) | 12 (4.6) |
| Aortic valve incompetence | 1 (0.4) | 0 | 0 |
| Diarrhea | 1 (0.4) | 0 | 1 (0.4) |
| Hepatitis | 0 | 0 | 1 (0.4) |
| Urinary tract infection | 0 | 1 (0.4) | 0 |
| Cystitis glandularis | 1 (0.4) | 0 | 0 |
| Vulvovaginal events‡‡ | 1 (0.4) | 0 | 2 (0.8) |
| Blood creatinine increased | 0 | 0 | 1 (0.4) |
| Hepatic enzymes increased | 0 | 1 (0.4) | 1 (0.4) |
| DKA (positively adjudicated) | 0 | 4 (1.5) | 4 (1.5) |
| Acetonemia§§ | 0 | 1 (0.4) | 1 (0.4) |
| Hypoglycemia | 3 (1.1) | 1 (0.4) | 0 |
| Severe hypoglycemia (positively adjudicated) | 2 (0.7) | 1 (0.4) | 0 |
Data are n or n (%) and include patients who received at least one dose of a study drug and include events that occurred up to 30 days after the last dose of double-blind study treatment.
↵*Death due to endocarditis, judged not related to study drug.
↵†Severe hypoglycemia was defined as any event that required assistance from another person or during which the patient lost consciousness or had a seizure. Hypoglycemia events include all those that occurred between first and last dose of study drug during the 52-week double-blind treatment period.
↵‡Diarrhea was mostly mild to moderate and transient.
↵§Renal events are listed in Supplementary Data.
||Volume depletion events are listed in Supplementary Data.
↵¶Included two breast cancer cases, one thyroid cancer, and one melanoma.
↵#Documented hypoglycemia was defined as a blood glucose level of ≤3.9 mmol/L (≤70 mg/dL) with or without hypoglycemia symptoms. In the sotagliflozin development program, hypoglycemia is considered an event of special interest, with a specialized case report form. Because analysis for hypoglycemia was based on data recorded in the case report form, investigators were asked to not submit hypoglycemic events on the adverse event case report form unless the episode met criteria for a serious adverse event.
↵**Nocturnal hypoglycemia was defined as positively adjudicated severe hypoglycemia or investigator-reported documented hypoglycemia (blood glucose level of ≤3.9 mmol/L [≤70 mg/dL] with or without hypoglycemia symptoms) that occurred between midnight and 5:59 a.m., regardless of whether the patient was awake during the event.
↵††All events of special interest leading to discontinuation were investigator reported except for DKA and severe hypoglycemia, which were positively adjudicated.
↵‡‡Vulvovaginal mycotic infection, vulvovaginits, and vulvovaginal pruritus.
↵§§Both cases of acetonemia were negatively adjudicated for DKA.