Table 3

Adverse events

EventEASE-2 and EASE-3 pooledEASE-3
Empagliflozin 10 mg (N = 491)Empagliflozin 25 mg (N = 489)Placebo (N = 484)Empagliflozin 2.5 mg (N = 241)Placebo (N = 241)
Any adverse event441 (89.8)428 (87.5)433 (89.5)194 (80.5)203 (84.2)
Drug-related adverse event221 (45.0)226 (46.2)158 (32.6)70 (29.0)56 (23.2)
Adverse event leading to discontinuation29 (5.9)18 (3.7)14 (2.9)8 (3.3)2 (0.8)
Serious adverse event64 (13.0)42 (8.6)44 (9.1)13 (5.4)16 (6.6)
Death0 (0.0)1 (0.2)0 (0.0)0 (0.0)0 (0.0)
Adverse events of interest
 Event consistent with genital infection63 (12.8)70 (14.3)21 (4.3)13 (5.4)6 (2.5)
 Event consistent with urinary tract infection47 (9.6)41 (8.4)41 (8.5)13 (5.4)11 (4.6)
 Event consistent with volume depletion12 (2.4)16 (3.3)8 (1.7)1 (0.4)3 (1.2)
 Lower limb amputation0001 (0.4)0
 Bone fracture14 (2.9)5 (1.0)8 (1.7)5 (2.1)2 (0.8)
 Acute renal impairment1 (0.2)4 (0.8)3 (0.6)00
 Hepatic event8 (1.6)8 (1.6)7 (1.4)1 (0.4)1 (0.4)
Adjudicated ketoacidosis and ketosis
 Patients with certain ketoacidosis21 (4.3)16 (3.3)6 (1.2)2 (0.8)3 (1.2)
  Patients with >1 event01000
  Number of events2118623
  Rate per 100 patient-years5.945.051.771.652.52
  Severity of event
   Severe events26101
   Moderate events138401
   Mild events64121
  Outcome of event
   Sequelae00100
   Fatal01000
 Patients with potential ketoacidosis15 (3.1)13 (2.7)6 (1.2)3 (1.2)1 (0.4)
  Number of events1614631
  Number of mild events1614631
 Patients with ketosis155 (31.6)178 (36.4)76 (15.7)41 (17.0)32 (13.3)
  Patients with BHB ≥3.8 mmol/L*21 (13.5)17 (9.6)4 (5.3)7 (17.1)2 (6.3)
 Patients with cases adjudicated as unclassifiable00000
Adjudicated severe hypoglycemia
 Patients with any event20 (4.1)13 (2.7)15 (3.1)3 (1.2)6 (2.5)
  Number of events33142196
  Rate per 100 patient-years9.544.026.357.665.22
  Patients with fatal events00000
  Patients with nocturnal events**102602
  • Data are n or n (%). Data are for patients who received at least one dose of a study drug and include events that occurred during treatment or within 7 days after the last receipt of a study drug.

  • *Percentage of patients with BHB ≥3.8 mmol/L is calculated based on the number of patients with ketosis.

  • **Onset between 0000 h and 0559 h.