Table 3. Summary of Adverse Events and Safety Parameters Through Safety Follow-Up 4 Weeks After Treatment Discontinuation.
| Parameter | Tirzepatide | Insulin lispro (n = 708) | |||
|---|---|---|---|---|---|
| 15 mg (n = 236) | 10 mg (n = 238) | 5 mg (n = 243) | Pooled (n = 717) | ||
| Participants with ≥1 serious adverse eventa | 15 (6.4) | 14 (5.9) | 15 (6.2) | 44 (6.1) | 77 (10.9) |
| Deathb | 1 (0.4) | 3 (1.3) | 3 (1.2) | 7 (1.0) | 11 (1.6) |
| Adverse event leading to study treatment discontinuation | 3 (1.3) | 4 (1.7) | 5 (2.1) | 12 (1.7) | 15 (2.1) |
| Participants with ≥1 adverse event leading to study treatment discontinuation | 22 (9.3) | 11 (4.6) | 10 (4.1) | 43 (6.0) | 17 (2.4) |
| Nausea | 6 (2.5) | 1 (0.4) | 3 (1.2) | 10 (1.4) | 0 |
| Vomiting | 5 (2.1) | 0 | 0 | 5 (0.7) | 0 |
| Weight decreased | 2 (0.8) | 0 | 0 | 2 (0.3) | 0 |
| Pancreatic enzymes increased | 2 (0.8) | 1 (0.4) | 0 | 3 (0.4) | 0 |
| Decreased appetite | 1 (0.4) | 1 (0.4) | 0 | 2 (0.3) | 0 |
| Dyspepsia | 1 (0.4) | 1 (0.4) | 0 | 2 (0.3) | 0 |
| Gastritis | 1 (0.4) | 1 (0.4) | 0 | 2 (0.3) | 0 |
| Acute coronary syndrome | 1 (0.4) | 0 | 0 | 1 (0.1) | 0 |
| COVID-19 | 0 | 0 | 0 | 0 | 3 (0.4) |
| Death | 0 | 0 | 1 (0.4) | 1 (0.1) | 1 (0.1) |
| Diarrhea | 0 | 0 | 2 (0.8) | 2 (0.3) | 0 |
| Lung neoplasm malignant | 0 | 0 | 0 | 0 | 2 (0.3) |
| Acute kidney injury | 0 | 1 (0.4) | 0 | 1 (0.1) | 0 |
| Participants with ≥1 treatment-emergent adverse eventc | 177 (75.0) | 168 (70.6) | 170 (70.0) | 515 (71.8) | 394 (55.6) |
| Treatment-emergent adverse events occurring in ≥5% of participants in any treatment group by preferred term | |||||
| Nausea | 61 (25.8) | 49 (20.6) | 33 (13.6) | 143 (19.9) | 8 (1.1) |
| Decreased appetite | 40 (16.9) | 28 (11.8) | 20 (8.2) | 88 (12.3) | 1 (0.1) |
| Vomiting | 30 (12.7) | 21 (8.8) | 11 (4.5) | 62 (8.6) | 4 (0.6) |
| Dyspepsia | 27 (11.4) | 27 (11.3) | 15 (6.2) | 69 (9.6) | 4 (0.6) |
| Diarrhea | 26 (11.0) | 36 (15.1) | 29 (11.9) | 91 (12.7) | 17 (2.4) |
| COVID-19 | 22 (9.3) | 19 (8.0) | 29 (11.9) | 70 (9.8) | 77 (10.9) |
| Constipation | 14 (5.9) | 8 (3.4) | 6 (2.5) | 28 (3.9) | 4 (0.6) |
| Urinary tract infection | 12 (5.1) | 2 (0.8) | 9 (3.7) | 23 (3.2) | 27 (3.8) |
| All gastrointestinal adverse events | 108 (45.8) | 114 (47.9) | 81 (33.3) | 303 (42.3) | 61 (8.6) |
| Other treatment-emergent adverse events of interest | |||||
| Major adverse cardiovascular events (adjudication confirmed)d | 3 (1.3) | 7 (2.9) | 5 (2.1) | 15 (2.1) | 12 (1.7) |
| Hypersensitivity | 6 (2.5) | 7 (2.9) | 4 (1.6) | 17 (2.4) | 9 (1.3) |
| Cholelithiasis | 4 (1.7) | 3 (1.3) | 2 (0.8) | 9 (1.3) | 2 (0.6) |
| Injection-site reactions | 4 (1.7) | 3 (1.3) | 1 (0.4) | 8 (1.1) | 1 (0.1) |
| Acute cholecystitis | 1 (0.4) | 1 (0.4) | 1 (0.4) | 3 (0.4) | 1 (0.1) |
| Diabetic retinopathye | 0 | 0 | 2 (0.8) | 2 (0.3) | 4 (0.6) |
| Adjudication-confirmed pancreatitis | 0 | 0 | 0 | 0 | 0 |
A serious adverse event was defined as any adverse event that resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent disability or incapacity, was a congenital anomaly or birth defect, or medical events that may not be immediately life-threatening or result in death or hospitalization but may jeopardize the participant or may require medical or surgical intervention to prevent one of the other outcomes previously listed.
Deaths were included as serious adverse events and discontinuations due to adverse event. No deaths were considered related to the study treatment by the investigator. All deaths were adjudicated by an external committee of physicians with cardiology expertise.
A treatment-emergent adverse event was defined as an untoward medical occurrence that emerged during the defined treatment period, having been absent before treatment, or worsens relative to the pretreatment state and does not necessarily have to have a causal relationship with this treatment.
Major adverse cardiovascular events include cardiovascular death, myocardial infarction, hospitalization due to unstable angina and stroke.
Confirmed by ophthalmoscopic examination.