Efficacy and safety of once-daily oral zenagamtide, a novel unimolecular GLP-1 and amylin receptor agonist, in adults with type 2 diabetes: a multicentre, randomised, parallel, double-blind, placebo-controlled, dose-finding, phase 2 trial
An erratum to this article was published (Lancet, 24 Oct 2026 ↗)
Authors' conclusion
In people with type 2 diabetes, once-daily oral zenagamtide showed clinically meaningful and significant improvements in HbA1c from baseline to week 36 compared with placebo at all three dose levels (6, 25, and 50 mg). The safety and tolerability of oral zenagamtide was consistent with other GLP-1 and amylin receptor agonists.
Study context
- Population
- Adults aged 18–75 years with T2D (HbA1c 7.0–10.0%), on stable metformin ± SGLT2i, BMI 23.0 to <50.0 kg/m²; 83 sites in 11 countriesrandomised 5:1
- Participants
- 186 adults
- Comparison
- Once-daily oral zenagamtide 6, 25 or 50 mg vs placebo
- Zenagamtide 6 mgn = 54
- Zenagamtide 25 mgn = 51
- Zenagamtide 50 mgn = 51
- Placebon = 30reference
- Primary endpoint
- Change in HbA1c from baseline
- Follow-up
- Week 36
Methodological detailsmulticentre, parallel, double-blind, placebo-controlled, dose-finding, phase 2, Randomisation stratified by HbA1c (<8.5% or ≥8.5%) and country (Japan or other), Starting dose 1.5 mg, escalated every 4 weeks to maintenance dose
- Multicentre
- Parallel
- Double-blind
- Placebo-controlled
- Dose-finding
- Phase 2
- Randomisation stratified by HbA1c (<8.5% or ≥8.5%) and country (Japan or other)
- Starting dose 1.5 mg, escalated every 4 weeks to maintenance dose
Primary result
As reported in the abstract
Change in HbA1c
Zenagamtide 6 mg
−0.9
estimated mean change · %
Zenagamtide 25 mg
−1.3
estimated mean change · %
Zenagamtide 50 mg
−1.4
estimated mean change · %
Each group vs placeboEstimated treatment difference, % (95% CI)P value
Zenagamtide 6 mg
−0.5(−1.04 to −0.04)
P = 0.033Zenagamtide 25 mg
−0.99(−1.49 to −0.49)
P = 0.0001Zenagamtide 50 mg
−1.09(−1.59 to −0.59)
P < 0.0001Safety
Gastrointestinal adverse events (most common)
Events
| Outcome | Zenagamtide 6 mg | Zenagamtide 25 mg | Zenagamtide 50 mg | Placebo |
|---|---|---|---|---|
| Serious adverse events | 2 | 2 | 3 | 0 |
- Serious adverse events — Serious AEs with zenagamtide overall
- 7 (4%) of 186
- Serious adverse events — Deaths
- 0
Original publication
Efficacy and safety of once-daily oral zenagamtide, a novel unimolecular GLP-1 and amylin receptor agonist, in adults with type 2 diabetes: a multicentre, randomised, parallel, double-blind, placebo-controlled, dose-finding, phase 2 trial. Lancet. Published 30 July 2026. doi:10.
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