Table 1

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 event216 (80.6)215 (81.7)209 (79.8)
Serious adverse event20 (7.5)27 (10.3)29 (11.1)
Severe adverse event7 (2.6)12 (4.6)12 (4.6)
Death1 (0.4)*00
Positively adjudicated adverse events
 ≥1 severe hypoglycemia event26 (9.7)17 (6.5)17 (6.5)
 ≥1 severe nocturnal hypoglycemia event**10 (3.7)10 (3.8)2 (0.8)
 ≥1 DKA event1 (0.4)9 (3.4)11 (4.2)
 ≥1 DKA event among CSII users1/160 (0.6)8/156 (5.1)7/157 (4.5)
 ≥1 DKA event among MDI users0/1081/107 (0.9)4/105 (3.8)
 Major adverse cardiovascular events
  Myocardial infarction or hospitalization for unstable angina3 (1.1)4 (1.5)0
  Stroke1 (0.4)01 (0.4)
  Heart failure hospitalization000
  Coronary revascularization2 (0.7)2 (0.8)0
 Drug-induced liver injury002 (0.8)
Events of special interest
 Any266 (99.3)260 (98.9)259 (98.9)
 Genital mycotic infection9 (3.4)24 (9.1)34 (13.0)
 Diarrhea18 (6.7)22 (8.4)27 (10.3)
 Urinary tract infection19 (7.1)26 (9.9)11 (4.2)
 Bone fracture10 (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 interest02 (0.8)2 (0.8)
 Amputation001 (0.4)
 Pancreatitis000
 Venous thrombotic event000
 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 discontinuation11 (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 incompetence1 (0.4)00
 Diarrhea1 (0.4)01 (0.4)
 Hepatitis001 (0.4)
 Urinary tract infection01 (0.4)0
 Cystitis glandularis1 (0.4)00
 Vulvovaginal events‡‡1 (0.4)02 (0.8)
 Blood creatinine increased001 (0.4)
 Hepatic enzymes increased01 (0.4)1 (0.4)
 DKA (positively adjudicated)04 (1.5)4 (1.5)
 Acetonemia§§01 (0.4)1 (0.4)
 Hypoglycemia3 (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.