Summary of patients experiencing AEs: safety population
| Safety parameter | Insulin 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 AE | 221 (74.2) | 222 (73.8) | 236 (80.3) |
| Any serious treatment-emergent AE | 11 (3.7) | 11 (3.7) | 14 (4.8) |
| Treatment-emergent AE | |||
| Leading to death | 1 (0.3) | 0 | 2 (0.7) |
| Leading to permanent discontinuation | 15 (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) |
| Nausea | 75 (25.2) | 5 (1.7) | 3 (1.0) |
| Vomiting | 26 (8.7) | 5 (1.7) | 6 (2.0) |
| Diarrhea | 20 (6.7) | 10 (3.3) | 4 (1.4) |
| Pancreatic enzyme increase** | |||
| Amylase | 0 | 0 | 0 |
| Lipase | 2 (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, N¶ | 332 | 395 | 600 |
| Events by hour of the day | |||
| 2300 to <0600 | 89 | 136 | 151 |
| 0600 to <1000 | 128 | 111 | 149 |
| 1000 to <1400 | 21 | 44 | 102 |
| 1400 to <1800 | 31 | 54 | 90 |
| 1800 to <2300 | 63 | 49 | 105 |
| Missing | 0 | 1 | 3 |
| Severe symptomatic hypoglycemia# | 0 | 2 (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.