Efficacy and safety of efsubaglutide alfa in individuals with type 2 diabetes (SUPER1): a randomised, double-blind, placebo-controlled, Phase IIb/III trial
An erratum to this article was published (Diabetologia, Jun 2026 ↗)
Authors' conclusion
Efsubaglutide alfa significantly improved glycaemic management and promoted weight loss in drug-naive individuals with type 2 diabetes, with a favourable safety profile. These results establish efsubaglutide alfa as a promising therapeutic option for type 2 diabetes and related metabolic disorders.
Study context
- Population
- Drug-naive adults newly diagnosed with T2D inadequately managed by diet and exercisePhase III stage
- Participants
- 297 adults
- Comparison
- Once-weekly SC efsubaglutide alfa vs placebo
- 1 mgn = 118
- 3 mgn = 117
- Placebon = 62reference
- Primary endpoint
- Change in HbA1c from baseline
- Follow-up
- Week 24
Methodological detailsdouble-blind, placebo-controlled, Phase IIb/III, operationally seamless adaptive design, two-stage, Phase III randomised 2:2:1, Phase IIb: 140 randomised 2:2:2:1 to 1 mg (n=41), 2 mg (n=39), 3 mg (n=41) or placebo (n=19) for 12 weeks; 1 and 3 mg selected as RP3Ds by independent data monitoring committee at interim analysis
- Double-blind
- Placebo-controlled
- Phase IIb/III
- Operationally seamless adaptive design
- Two-stage
- Phase III randomised 2:2:1
- Phase IIb: 140 randomised 2:2:2:1 to 1 mg (n=41), 2 mg (n=39), 3 mg (n=41) or placebo (n=19) for 12 weeks; 1 and 3 mg selected as RP3Ds by independent data monitoring committee at interim analysis
Primary result
As reported in the abstract
Estimated treatment difference
−13.71 mmol/mol (−1.26%) (95% CI −17.39 to −10.06)
1 mg
Estimated treatment difference
−18.36 mmol/mol (−1.68%) (95% CI −22.08 to −14.64)
3 mg
1 mg
−18.91 mmol/mol
1.73%
95% CI −20.98–-16.83
3 mg
−23.50 mmol/mol
2.15%
95% CI −25.68–-21.31
Secondary outcomes
Mmol/l
| Outcome | 1 mg | 3 mg | Estimated treatment difference (mmol/l) (95% CI) | |
|---|---|---|---|---|
| FPG reduction from baseline1 mgvs Placebo | 2.04 (95% CI −2.40–-1.68) | 2.49 (95% CI −2.87–-2.11) | −1.71 (−2.34 to −1.07) | |
| FPG reduction from baseline3 mgvs Placebo | −2.16 (−2.80 to −1.52) | |||
| 2 h postprandial plasma glucose reduction from baseline1 mgvs Placebo | 3.7 (95% CI −4.42–-3.03) | 4.6 (95% CI −5.36–-3.86) | −3.2 (−4.41 to −1.98) | |
| 2 h postprandial plasma glucose reduction from baseline3 mgvs Placebo | −4.1 (−5.28 to −2.88) | |||
| −10−505Difference, mmol/l (linear scale) |
| Outcome | 1 mg | 3 mg | Estimated treatment difference (95% CI) | |
|---|---|---|---|---|
| Body weight decrease1 mgvs Placebo | 0.97% (95% CI −1.76–-0.18) | 3.14% (95% CI −3.98–-2.31) | 0.97% (−0.41 to 2.35) | |
| Body weight decrease3 mgvs Placebo | −2.18% (−3.30 to −1.05) | |||
| −4−2024Difference (linear scale) |
| Outcome | 1 mg | 3 mg |
|---|---|---|
| HbA1c <53.0 mmol/mol (7.0%) achieved | 56% (95% CI 47–65) | 68% (95% CI 59–76) |
- HbA1c <53.0 mmol/mol (7.0%) achieved: p<0.001 for each dose
Safety
Adverse events
- GI symptoms (nausea, vomiting, diarrhoea, decreased appetite) were the most common AEs, mostly mild to moderate
Original publication
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