Comparison of Liraglutide, Semaglutide, and Tirzepatide.11–23
| Parameter | Liraglutide | Semaglutide | Tirzepatide |
|---|---|---|---|
| Drug class | GLP-1 receptor agonist | GLP-1 receptor agonist | Dual GIP and GLP-1 receptor agonist |
| Year of approval (US-FDA) | 2014 | 2021 | 2023 |
| Route | Subcutaneous | Subcutaneous | Subcutaneous |
| Approved in adolescents | Approved (≥12 years age) | Approved (≥12 years age) | Not yet approved |
| Frequency | Daily | Weekly | Weekly |
| Dosing | 3.0 mg | 2.4 mg | Starting at 2.5 mg, titrated up to 15 mg |
| Mechanism of action | Activates GLP-1 receptors → enhances insulin secretion, suppresses glucagon, slows gastric emptying, promotes satiety | Activates GLP-1 receptors → enhances insulin secretion, suppresses glucagon, slows gastric emptying, promotes satiety | Activates both GIP and GLP-1 receptors → synergistic effect on insulin secretion, satiety, and weight loss |
| Half-life (t 1/2) | ~13 hours | ~7 days | ~5 days |
| Average weight loss (%) | 5%–8% | 12%–15% | 15%–20% |
| Glycemic control (HbA1c reduction) | 1.0%–1.5% | 1.5%–1.8% | 2.0%–2.4% |
| Adverse effects | Primarily gastrointestinal | Primarily gastrointestinal | Primarily gastrointestinal |
| Contraindications | Personal or family history of MTC; patients with MEN 2; and pregnancy | Personal or family history of MTC; patients with MEN 2; and pregnancy | Personal or family history of MTC; patients with MEN 2; and pregnancy |
| Other approved indications | T2DM
Cardiovascular risk reduction |
T2DM
Cardiovascular risk reduction |
T2DM |
| Cardiovascular outcome trials | LEADER: ↓ MACE risk in T2DM | SUSTAIN and SELECT: ↓ CV events in T2DM and obesity | SURPASS-CVOT: ongoing |
| Obesity trials | STEP 8 and SCALE | STEP 1, STEP 3, STEP 4, and STEP 8 | SURMOUNT 1 and SURMOUNT 3 |
| Monthly cost (US dollars) | ~$1,349 | $998–$1,400 (depending on dose/brand) | $1,000–$1,500 |
| US boxed warning | Thyroid C-cell tumors (based on rodent studies) | Thyroid C-cell tumors (based on rodent studies) | Thyroid C-cell tumors (based on rodent studies) |