Semaglutide (Ozempic/Wegovy) and dulaglutide (Trulicity) are both GLP-1 receptor agonists approved for type 2 diabetes and, in semaglutide’s case, weight management. They differ significantly in potency, dosing frequency, weight loss efficacy, and cardiovascular outcomes data.
| Parameter | Semaglutide (SC) | Dulaglutide |
|---|
| Brand name | Ozempic, Wegovy | Trulicity |
| Manufacturer | Novo Nordisk | Eli Lilly |
| Structure | Modified GLP-1 (31 aa) | GLP-1(7-37) + IgG4 Fc fusion |
| Molecular weight | ~4,113 Da | ~63,000 Da |
| Half-life | ~165 hours (7 days) | ~120 hours (5 days) |
| Dosing frequency | Once weekly | Once weekly |
| Maximum approved dose | 2.0 mg (Ozempic), 2.4 mg (Wegovy) | 1.5 mg (3.0 mg studied) |
| Trial | Semaglutide | Dulaglutide | Difference |
|---|
| AWARD-11 vs SUSTAIN-7 | −1.8% (1.0 mg) | −1.3% (1.5 mg) | Semaglutide superior |
| AWARD-11 vs PIONEER-10 | −1.5% (0.5 mg) | −1.3% (1.5 mg) | Similar |
| Matching indirect comparison | −1.5 to −1.8% | −1.1 to −1.3% | Semaglutide numerically superior |
| Parameter | Semaglutide 2.4 mg | Dulaglutide 1.5 mg | Dulaglutide 3.0 mg |
|---|
| Mean weight loss | −14.9% | −4.6% | −7.5% |
| ≥5% weight loss | 83% | 52% | 65% |
| ≥10% weight loss | 66% | 25% | 38% |
| Weight loss category | Substantial | Modest | Moderate |
Semaglutide produces approximately 2–3× greater weight loss than dulaglutide at respective maximum doses.
| Trial | Semaglutide | Dulaglutide |
|---|
| SELECT (CVOT) | 20% MACE reduction (HR 0.80) | — |
| SUSTAIN-6 | 26% MACE reduction (HR 0.74) | — |
| REWIND | 12% MACE reduction (HR 0.88) | — |
| LEADER (liraglutide comparator) | — | Similar to dulaglutide profile |
Key differences:
- Semaglutide SELECT trial included non-diabetic patients (first for GLP-1 RA)
- Dulaglutide REWIND included lower-risk population
- Both demonstrated CV benefit, but semaglutide showed larger effect sizes
| Week | Dose |
|---|
| 1–4 | 0.25 mg weekly |
| 5–8 | 0.5 mg weekly |
| 9+ | 1.0 mg weekly |
| 9+ | 2.0 mg weekly (maximum) |
| Week | Dose |
|---|
| 1–4 | 0.75 mg weekly |
| 5+ | 1.5 mg weekly (standard) |
| 5+ | 3.0 mg weekly (maximum) |
| 5+ | 4.5 mg weekly (maximum, AWARD-11) |
| Feature | Semaglutide | Dulaglutide |
|---|
| Administration window | ±2 days from scheduled day | ±3 days from scheduled day |
| Missed dose rule | If <2 days late, take when remembered | If <3 days late, take when remembered |
| Pre-filled pen | Yes (single-dose pen) | Yes (single-dose pen) |
| Dose adjustment | Multiple dose options | 3 fixed doses |
| Adverse Event | Semaglutide 2.4 mg | Dulaglutide 1.5 mg |
|---|
| Nausea | 30–44% | 18–25% |
| Diarrhea | 15–20% | 12–18% |
| Vomiting | 15–20% | 8–14% |
| Constipation | 10–15% | 8–12% |
| Abdominal pain | 8–12% | 8–12% |
Semaglutide at maximum dose produces more GI side effects than dulaglutide, largely due to greater potency.
| Event | Semaglutide | Dulaglutide |
|---|
| Injection site reactions | 1–2% | 2–5% |
| Headache | 5–8% | 5–8% |
| Fatigue | 3–5% | 3–5% |
| Pancreatitis | Rare (<0.5%) | Rare (<0.5%) |
| Gallbladder events | 2–3% | 1–2% |
| eGFR | Semaglutide | Dulaglutide |
|---|
| ≥30 | No adjustment | No adjustment |
| 15–29 | Use with caution | Use with caution |
| <15/dialysis | Limited data | Limited data |
- Semaglutide: No adjustment for mild-moderate; not studied in severe
- Dulaglutide: No adjustment for mild-moderate; not studied in severe
| Population | Semaglutide Evidence | Dulaglutide Evidence |
|---|
| Established ASCVD | SUSTAIN-6, SELECT | REWIND |
| Heart failure | SELECT subgroup | Limited data |
| CKD | SELECT subgroup | REWIND subgroup |
| Parameter | Semaglutide | Dulaglutide |
|---|
| List price (monthly) | $900–1,300 | $800–1,000 |
| Insurance coverage | Varies by indication | Generally covered |
| Biosimilars | Under development | Under development |
| Self-injection pen | Yes | Yes |
| Oral option | Yes (Rybelsus) | No |
- Frías JP, et al. “Efficacy and safety of semaglutide vs dulaglutide (AWARD-11).” Lancet 2021;398:1811-1824.
- Gerstein HC, et al. “Dulaglutide and cardiovascular outcomes (REWIND).” Lancet 2019;394:122-130.
- Lincoff AM, et al. “Semaglutide and cardiovascular outcomes in obesity without diabetes (SELECT).” NEJM 2023;389:2221-2232.
