PMID-33397768 – Dulaglutide AWARD-11 Higher Doses
Frias JP, Bonora E, Nevarez Ruiz L, et al. Efficacy and Safety of Dulaglutide 3.0 mg and 4.5 mg Versus Dulaglutide 1.5 mg in Metformin-Treated Patients With Type 2 Diabetes in a Randomized Controlled Trial (AWARD-11). Diabetes Care. 2021;44(3):765-773.
Quick Reference
| Property | Value |
|---|---|
| PMID | 33397768 |
| DOI | 10.2337/dc20-1473 |
| Year | 2021 |
| Journal | Diabetes Care |
| Study Type | RCT (Phase 3) |
| Evidence Level | I |
| Sample | n=1,842 patients with T2D on metformin |
| Peptide(s) Studied | Dulaglutide |
Key Findings
- At 36 weeks, HbA1c reductions were: -1.53% (3.0 mg), -1.64% (4.5 mg), -1.39% (1.5 mg)
- Dulaglutide 4.5 mg was superior to 1.5 mg for HbA1c reduction (P<0.001)
- Weight loss at 36 weeks: -3.0 kg (1.5 mg), -4.0 kg (3.0 mg), -4.6 kg (4.5 mg)
- Dulaglutide 4.5 mg was superior to 1.5 mg for weight loss (-1.6 kg difference, P<0.001)
- Higher proportions achieved HbA1c <7.0% with 3.0 mg (78%) and 4.5 mg (80%) vs. 1.5 mg (72%)
- GI adverse events were modestly higher at 4.5 mg but remained manageable
- No new safety signals with higher doses; no disproportionate increase in severe hypoglycemia
Study Design
Randomized, double-blind, parallel-group, phase 3 trial. Patients with T2D (HbA1c 7.5-11.0%) on metformin were randomized 1:1:1 to dulaglutide 1.5 mg, 3.0 mg, or 4.5 mg once weekly for 36 weeks, with a 16-week extension (52 weeks total). Primary endpoint was HbA1c change from baseline at 36 weeks (superiority of 3.0 mg and 4.5 mg vs. 1.5 mg).
Limitations
- No placebo arm (all received active treatment)
- Relatively short primary endpoint (36 weeks)
- All patients were on metformin background; may not generalize to other combinations
- Head-to-head comparison with other GLP-1 RAs not performed
Clinical Relevance
AWARD-11 demonstrated a clear dose-response for dulaglutide up to 4.5 mg, expanding the approved dosing range. The additional ~1.6 kg weight loss and ~0.25% HbA1c improvement from 1.5 to 4.5 mg provides clinical flexibility. However, even at the highest dose, dulaglutide's weight loss remains modest compared to newer agents (semaglutide 2.4 mg, tirzepatide). This trial informs practitioners about available dose escalation options within the dulaglutide framework.
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#research #RCT #evidence-level-I #metabolic #dulaglutide