Table 3

Summary of patients experiencing AEs: safety population

Safety parameterInsulin glargine with or without metformin plus
Lixisenatide 20 µg once daily (n = 298)Insulin glulisine once daily (n = 301)Insulin glulisine thrice daily (n = 294)
Any treatment-emergent AE221 (74.2)222 (73.8)236 (80.3)
Any serious treatment-emergent AE11 (3.7)11 (3.7)14 (4.8)
Treatment-emergent AE
 Leading to death1 (0.3)02 (0.7)
 Leading to permanent discontinuation15 (5.0)2 (0.7)3 (1.0)
Gastrointestinal AEs (system organ class and preferred term)105 (35.2)26 (8.6)22 (7.5)
 Nausea75 (25.2)5 (1.7)3 (1.0)
 Vomiting26 (8.7)5 (1.7)6 (2.0)
 Diarrhea20 (6.7)10 (3.3)4 (1.4)
Pancreatic enzyme increase**
 Amylase000
 Lipase2 (0.7)1 (0.3)3 (1.0)
Hypoglycemia
 Symptomatic hypoglycemia*107 (35.9)140 (46.5)154 (52.4)
 Symptomatic hypoglycemia per protocol§98 (32.9)117 (38.9)132 (44.9)
 Symptomatic hypoglycemia events per protocol, N332395600
  Events by hour of the day
   2300 to <060089136151
   0600 to <1000128111149
   1000 to <14002144102
   1400 to <1800315490
   1800 to <23006349105
   Missing013
 Severe symptomatic hypoglycemia#02 (0.7)0
Exploratory analysis
 Estimated rate ratio lixisenatide-to-insulin glulisine for
   Symptomatic hypoglycemia events (95% CI)0.75 (0.53, 1.06)0.49 (0.34, 0.69)
   Nocturnal symptomatic hypoglycemia (95% CI)0.58 (0.37, 0.90)0.47 (0.30, 0.73)
  • All data are n (%) patients with events, unless otherwise stated.

  • **Defined as more than twice the upper limit of normal confirmed by repeat measurement.

  • *Any symptomatic hypoglycemia reported as clinically meaningful by the study investigator regardless of plasma glucose.

  • P = 0.01 vs. lixisenatide (Fisher exact test; post hoc analysis).

  • P = 0.0001 vs. lixisenatide (Fisher exact test; post hoc analysis).

  • §Symptomatic hypoglycemia accompanied by glucose <3.3 mmol/L (<60 mg/dL) or prompt recovery with oral carbohydrate.

  • P = 0.0031 vs. lixisenatide (Fisher exact test; post hoc analysis).

  • ¶Number of hypoglycemia events was analyzed using negative binomial regression with a log-link function and the logarithm of the time period for which a hypoglycemic episode was considered treatment-emergent as offset, with treatment, randomization strata of HbA1c, randomization strata of metformin use, and country as fixed effects.

  • #Plasma glucose <2.0 mmol/L (<36 mg/dL) or with prompt recovery after oral carbohydrate, intravenous glucose, or glucagon administration; 70% of patients receiving lixisenatide or insulin glulisine once daily administered their dose in the evening.