Efficacy and safety of once-weekly subcutaneous zenagamtide, a novel unimolecular GLP-1 and amylin receptor agonist, in type 2 diabetes: a multicentre, randomised, parallel, double-blind, placebo-controlled, dose-finding, phase 2 trial
Authors' conclusion
In people with type 2 diabetes, once-weekly subcutaneous zenagamtide 0.4-40 mg demonstrated clinically meaningful and significant improvements in change in HbA1c from baseline to week 36 compared with placebo, with a safety and tolerability profile consistent with that of other GLP-1-based and amylin-based therapies.
Study context
- Population
- Adults aged 18–75 years with T2D (HbA1c 7.0–10.0%), on stable metformin with or without SGLT2i, BMI 23.0 to <50.0 kg/m²; 83 sites in 11 countries261 exposed to treatment
- Participants
- 262 adults
- Comparison
- Once-weekly SC zenagamtide vs placebo
- Zenagamtide 0.4 mgn = 38
- Zenagamtide 1.5 mgn = 36
- Zenagamtide 5 mgn = 37
- Zenagamtide 10 mgn = 38
- Zenagamtide 20 mgn = 38
- Zenagamtide 40 mgn = 38
- Placebon = 37reference
- Primary endpoint
- Change in HbA1c from baseline
- Follow-up
- Week 36
Methodological detailsmulticentre, parallel, double-blind, placebo-controlled, dose-finding, phase 2, 3-week screening, 36-week intervention, 4-week follow-up, Randomised 6:1 to zenagamtide or placebo, then 1:1:1:1:1:1 to six dose levels; stratified by HbA1c (<8.5% or ≥8.5%) and country (Japan or other), Starting dose 0.2 mg, escalated every 4 weeks to maintenance dose
- Multicentre
- Parallel
- Double-blind
- Placebo-controlled
- Dose-finding
- Phase 2
- 3-week screening, 36-week intervention, 4-week follow-up
- Randomised 6:1 to zenagamtide or placebo, then 1:1:1:1:1:1 to six dose levels; stratified by HbA1c (<8.5% or ≥8.5%) and country (Japan or other)
- Starting dose 0.2 mg, escalated every 4 weeks to maintenance dose
Primary result
As reported in the abstract
Zenagamtide 0.4 mg
−0.9
%
Zenagamtide 40 mg
−1.7
%
Each group vs placeboEstimated treatment difference, % (95% CI)P value
Zenagamtide 0.4 mg
−0.77(−1.26 to −0.28)
P = 0.0021Zenagamtide 40 mg
−1.56(−2.05 to −1.07)
P < 0.0001Further findings
Baseline HbA1c, all groups
- Mean HbA1c at baseline across all groups
- 7.8% (SD 0.8)
Adverse events and deaths
- Deaths
- 0
- Most adverse events were gastrointestinal and mild to moderate in severity
Safety
| Outcome | Values |
|---|---|
| Serious adverse events | Zenagamtide 0.4 mg 4 events · Zenagamtide 1.5 mg 3 events · Zenagamtide 5 mg 2 events · Zenagamtide 10 mg 5 events · Zenagamtide 20 mg 3 events · Zenagamtide 40 mg 1 events · Placebo 3 events |
- Serious adverse events — Participants with serious adverse events, overall
- 21 (8%) of 261
Original publication
Efficacy and safety of once-weekly subcutaneous zenagamtide, a novel unimolecular GLP-1 and amylin receptor agonist, in type 2 diabetes: a multicentre, randomised, parallel, double-blind, placebo-controlled, dose-finding, phase 2 trial. Lancet. Published 30 July 2026. doi:10.
Composed by AI from the published abstract and checked against it. How Briefs are made →