Summary of adverse events and events of special interest during the overall treatment period (baseline to 52 weeks)
| Placebo (n = 258) | Sotagliflozin 200 mg (n = 261) | Sotagliflozin 400 mg (n = 263) | |
|---|---|---|---|
| Any adverse event | 158 (61.2) | 178 (68.2) | 181 (68.8) |
| Serious adverse event | 17 (6.6) | 26 (10.0) | 21 (8.0) |
| Severe adverse event | 4 (1.6) | 7 (2.7) | 10 (3.8) |
| Death | 2 (0.8)* | 0 | 0 |
| Positively adjudicated adverse events | |||
| ≥1 episode of severe hypoglycemia† | 13 (5.0) | 13 (5.0) | 6 (2.3) |
| ≥1 episode of severe nocturnal hypoglycemia†** | 3 (1.2) | 1 (0.4) | 2 (0.8) |
| ≥1 episode of DKA | 0 | 6 (2.3) | 9 (3.4) |
| ≥1 episode of DKA among CSII users | 0 | 1/68 (1.5) | 5/67 (7.5) |
| ≥1 episode of DKA among MDI users | 0 | 5/193 (2.6) | 4/196 (2.0) |
| MACE | |||
| Myocardial infarction or hospitalization for unstable angina | 0 | 1 (0.4) | 2 (0.8) |
| Stroke | 1 (0.4) | 0 | 0 |
| Hospitalization for heart failure | 0 | 0 | 0 |
| Coronary revascularization | 0 | 2 (0.8) | 1 (0.4) |
| Drug-induced liver injury | 1 (0.4) | 0 | 0 |
| Acidosis-related adverse events‡ | |||
| Any | 3 (1.2) | 23 (8.8) | 30 (11.4) |
| Serious | 0 | 7 (2.7) | 13 (4.9) |
| Events of special interest | |||
| Any | 254 (98.4) | 255 (97.7) | 261 (99.2) |
| Volume depletion§ | 1 (0.4) | 6 (2.3) | 2 (0.8) |
| Genital mycotic infection | 6 (2.3) | 24 (9.2) | 29 (11.0) |
| Urinary tract infection | 13 (5.0) | 11 (4.2) | 18 (6.8) |
| Diarrhea‖ | 9 (3.5) | 12 (4.6) | 19 (7.2) |
| Pancreatitis | 0 | 0 | 1 (0.4) |
| Bone fracture | 8 (3.1) | 6 (2.3) | 5 (1.9) |
| Venous thrombotic event | 0 | 0 | 0 |
| Renal event¶ | 3 (1.2) | 1 (0.4) | 3 (1.1) |
| Malignancy | 2 (0.8) | 1 (0.4) | 1 (0.4) |
| Amputation | 0 | 1 (0.4) | 0 |
| Any documented hypoglycemia (SMBG ≤3.9 mmol/L)# | 252 (97.7) | 255 (97.7) | 260 (98.9) |
| Any nocturnal documented hypoglycemia** | 196 (76.0) | 189 (72.4) | 201 (76.4) |
| Any SMBG value ≤3.0 mmol/L | 230 (89.1) | 231 (88.5) | 238 (90.5) |
| Any adverse event leading to discontinuation | 9 (3.5) | 10 (3.8) | 18 (6.8) |
| Any event of special interest leading to discontinuation†† | 6 (2.3) | 7 (2.7) | 12 (4.6) |
| DKA (positively adjudicated) | 0 | 0 | 4 (1.5) |
| Diarrhea | 1 (0.4) | 2 (0.8) | 2 (0.8) |
| Genital mycotic infection | 2 (0.8) | 3 (1.1) | 2 (0.8) |
| Urinary tract infection | 0 | 2 (0.8) | 0 |
| Potential drug-induced liver injury | 0 | 0 | 1 (0.4) |
| Severe hypoglycemia (positively adjudicated) | 0 | 0 | 0 |
| Stroke | 1 (0.4) | 0 | 0 |
| Neoplasm | 2 (0.8) | 0 | 1 (0.4) |
Data are n (%) or n/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.
↵*One death was due to cardiopulmonary failure and the other to a malignant lung neoplasm.
↵†Severe hypoglycemia was defined as any hypoglycemic event that required assistance from another person or during which the patient lost consciousness or had a seizure. Hypoglycemic events include all those that occurred between administration of the first and last dose of study drug during the 52-week double-blind treatment period.
↵‡Acidosis-related adverse events, whether serious or nonserious, are adverse events that satisfy the trigger terms for metabolic acidosis, which are the following Medical Dictionary for Regulatory Activities preferred terms: acetonemia, acidosis, acidosis hyperchloremic, blood ketone body, blood ketone body increased, blood ketone body present, DKA, diabetic hyperglycemia coma, diabetic ketoacidotic hyperglycemic coma, diabetic metabolic decompensation, diabetic coma, hyperglycemic coma, hyperglycemic seizure, hyperglycemic unconsciousness, ketoacidosis, ketosis, lactic acidosis, metabolic acidosis, renal tubular acidosis, uremic acidosis, urine ketone body, and urine ketone body present.
↵§Volume depletion events are listed in the Supplementary Data.
↵‖Diarrhea was mostly mild to moderate and transient.
↵¶Renal events are listed in the Supplementary Data.
↵#Documented hypoglycemia was defined as blood glucose ≤70 mg/dL with or without symptoms of hypoglycemia. In the sotagliflozin development program, hypoglycemia is considered to be an event of special interest and requires a specialized case report form. Because analysis of hypoglycemia was based on data recorded on case report forms, 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 ≤70 mg/dL with or without symptoms of hypoglycemia) 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 reported by investigators, except for DKA and severe hypoglycemia, which were positively adjudicated.