GLP-1 receptor agonists represent the most impactful class of incretin-based therapies for type 2 diabetes and obesity. This comparison evaluates the major agents across pharmacology, efficacy, safety, and practical considerations.
| Agent | Brand | Route | Frequency | Half-life | Year Approved |
|---|
| Exenatide | Byetta | SC | Twice daily | 2.4 hours | 2005 |
| Exenatide ER | Bydureon | SC | Once weekly | 5–6 days | 2012 |
| Liraglutide | Victoza | SC | Once daily | 13 hours | 2010 |
| Liraglutide | Saxenda | SC | Once daily | 13 hours | 2014 |
| Albiglutide | Tanzeum | SC | Once weekly | 5 days | 2014 |
| Dulaglutide | Trulicity | SC | Once weekly | 4.7 days | 2014 |
| Semaglutide | Ozempic | SC | Once weekly | 165 hours | 2017 |
| Semaglutide | Rybelsus | Oral | Once daily | 165 hours | 2019 |
| Semaglutide | Wegovy | SC | Once weekly | 165 hours | 2021 |
| Tirzepatide | Mounjaro | SC | Once weekly | ~5 days | 2022 |
| Tirzepatide | Zepbound | SC | Once weekly | ~5 days | 2023 |
| Oral semaglutide | Amylyx | Oral | Once daily | 165 hours | 2024 |
All agents in this class share the core mechanism:
- Pancreatic effects: Glucose-dependent insulin secretion, glucagon suppression
- GI effects: Delayed gastric emptying, satiety signaling
- Central effects: Appetite suppression, reward pathway modulation
- Cardiovascular: Reduced MACE in high-risk populations
Tirzepatide activates both GLP-1 and GIP receptors, producing enhanced metabolic effects through dual incretin signaling.
| Agent | Dose | HbA1c Reduction | Trial |
|---|
| Exenatide | 10 µg BID | −0.8% to −1.0% | AMIGO |
| Liraglutide | 1.8 mg QD | −1.0% to −1.3% | LEAD |
| Dulaglutide | 1.5 mg QW | −1.0% to −1.4% | AWARD |
| Semaglutide | 1.0 mg QW | −1.3% to −1.6% | SUSTAIN |
| Semaglutide | 2.0 mg QW | −1.5% to −1.8% | SUSTAIN |
| Tirzepatide | 15 mg QW | −1.6% to −2.0% | SURPASS |
| Agent | Dose | Weight Change | Trial |
|---|
| Exenatide | 10 µg BID | −1.6 to −2.8 kg | AMIGO |
| Liraglutide | 1.8 mg QD | −2.0 to −3.5 kg | LEAD |
| Dulaglutide | 1.5 mg QW | −1.0 to −2.0 kg | AWARD |
| Semaglutide | 1.0 mg QW | −3.5 to −5.0 kg | SUSTAIN |
| Semaglutide | 2.0 mg QW | −5.0 to −7.0 kg | SUSTAIN |
| Tirzepatide | 15 mg QW | −5.0 to −7.5 kg | SURPASS |
| Agent | Indication | Dose | Weight Loss (% body weight) | Trial |
|---|
| Liraglutide (Saxenda) | Obesity | 3.0 mg QD | −5.0% to −8.0% | SCALE |
| Semaglutide (Wegovy) | Obesity | 2.4 mg QW | −12.0% to −15.0% | STEP |
| Tirzepatide (Zepbound) | Obesity | 15 mg QW | −15.0% to −21.0% | SURMOUNT |
| Parameter | Exenatide | Liraglutide | Semaglutide | Tirzepatide |
|---|
| Half-life | 2.4 hours | 13 hours | 165 hours | ~5 days |
| Bioavailability | 65% | 55% | 89% | ~80% |
| Peak (SC) | 2.1 hours | 8–12 hours | 1–3 days | 24–48 hours |
| Frequency | BID or QW | QD | QW or daily oral | QW |
| Protein binding | <8% | >98% | >99% | >99% |
| Agent | Nausea | Diarrhea | Vomiting | Constipation |
|---|
| Exenatide | 35–44% | 13–17% | 11–15% | 8–10% |
| Liraglutide | 25–39% | 12–15% | 10–15% | 5–8% |
| Dulaglutide | 12–18% | 8–12% | 5–8% | 5–8% |
| Semaglutide | 15–20% | 8–12% | 8–12% | 5–10% |
| Tirzepatide | 12–18% | 10–15% | 5–10% | 5–8% |
| Event | Class Risk | Monitoring |
|---|
| Pancreatitis | Rare (0.1–0.3%) | Lipase, amylase if symptoms |
| Gallbladder disease | Increased with weight loss | Symptoms, ultrasound |
| Medullary thyroid carcinoma | Boxed warning (rodent data) | Family history screening |
| Hypoglycemia | Low (as monotherapy) | More with insulin/SU |
| Injection site reactions | Common | Rotation technique |
| Agent | Starting Dose | Maintenance | Maximum | Titration |
|---|
| Exenatide | 5 µg BID | 10 µg BID | 10 µg BID | 4 weeks |
| Liraglutide (DM) | 0.6 mg QD | 1.2–1.8 mg QD | 1.8 mg QD | 1–2 weeks |
| Liraglutide (Obesity) | 0.6 mg QD | 3.0 mg QD | 3.0 mg QD | 4 weeks |
| Dulaglutide | 0.75 mg QW | 1.5 mg QW | 4.5 mg QW | 4 weeks |
| Semaglutide (DM) | 0.25 mg QW | 0.5–2.0 mg QW | 2.0 mg QW | 4 weeks |
| Semaglutide (Obesity) | 0.25 mg QW | 2.4 mg QW | 2.4 mg QW | 16 weeks |
| Tirzepatide | 2.5 mg QW | 5–15 mg QW | 15 mg QW | 4 weeks |
| Agent | MACE Reduction | Trial | Population |
|---|
| Liraglutide | 22% | LEADER | High CV risk |
| Semaglutide | 26% | SUSTAIN-6 | High CV risk |
| Dulaglutide | 12% | REWIND | Mixed CV risk |
| Exenatide ER | 11% | EXSCEL | Broad population |
| Tirzepatide | Pending | SURPASS-CVOT | Ongoing |
| Agent | Monthly Cost (list) | Annual Cost |
|---|
| Exenatide (Byetta) | $800–1,000 | $9,600–12,000 |
| Liraglutide (Victoza) | $900–1,200 | $10,800–14,400 |
| Dulaglutide (Trulicity) | $900–1,100 | $10,800–13,200 |
| Semaglutide (Ozempic) | $900–1,100 | $10,800–13,200 |
| Semaglutide (Wegovy) | $1,300–1,500 | $15,600–18,000 |
| Tirzepatide (Mounjaro) | $1,000–1,200 | $12,000–14,400 |
| Tirzepatide (Zepbound) | $1,000–1,200 | $12,000–14,400 |
- Tirzepatide 15 mg (−1.6 to −2.0%)
- Semaglutide 2.0 mg (−1.5 to −1.8%)
- Semaglutide 1.0 mg (−1.3 to −1.6%)
- Tirzepatide 15 mg (−15 to −21%)
- Semaglutide 2.4 mg (−12 to −15%)
- Liraglutide 3.0 mg (−5 to −8%)
- Semaglutide (strongest SUSTAIN-6 data)
- Liraglutide (LEADER trial)
- Dulaglutide (REWIND trial)
- Exenatide (generic availability)
- Dulaglutide (biosimilar development)
- Semaglutide (Wegovy savings cards)
- Drucker DJ. “Mechanisms of Action and Therapeutic Application of Glucagon-like Peptide-1.” Cell Metab 2018;27:740-756.
- Nauck MA, et al. “Incretin-Based Therapies and Cardiovascular Outcomes.” NEJM 2024;390:863-874.
