Trial reportDiabetes, obesity & metabolism2025

Efficacy and safety of Efsubaglutide Alfa in "overrun" patients in the SUPER2 trial: A post-hoc analysis for comprehensive evaluation.

Weiping Jia, Fan Jiang, Yulong Xu, Yiming Li, Yuqian Bao, Qinghua Wang

Abstract readRandomized Controlled TrialClinical Trial, Phase IIClinical Trial, Phase III
PubMed Publisher
In one paragraph

Trial report in Diabetes, obesity & metabolism, 2025. The graph read 5 numbers from its abstract, feeding 2 cells of the map: it finds no clear difference in 2. Not yet cited in PubMed.

5numbers the graph read from it
2cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

Ratios

← favours the treatmentfavours the comparator →
24101 · no effect
HbA1c <7.0%Efsubaglutide Alfa 1 mg vs placebofavours the comparator · t2dfeeds one cell of the map
OR 8.30<0.0001
HbA1c <7.0% was achieved by 56.3% versus 11.1% with placebo (p < 0.0001; odds ratio 8.3).

Differences

← favours the treatmentfavours the comparator →
-1.911.590 · no effect
Body weightEfsubaglutide Alfa 1 mg vs placebono clear difference · t2dfeeds one cell of the map
Δ -0.720.137
Body weight reduction was modest and not significant (-2.8% vs. -1.3%; LSM -0.72 kg; p = 0.137).
Glycemic controlfavours the treatment · against placebo · t2dfeeds one cell of the map
decrease -1.69-1.91 to -1.47
RESULTS: At week 24, HbA1c decreased by -1.69% (95% CI -1.91 to -1.47) with Efsubaglutide Alfa 1 mg versus -0.74% (-0.96 to -0.52) with placebo, a placebo-corrected difference of -0.95% (95% CI -1.25 to -0.65; p < 0.0001).
HbA1cEfsubaglutide Alfa 1 mg vs placebofavours the treatment · t2dfeeds one cell of the map
Δ -0.95-1.25 to -0.65p < 0.0001
RESULTS: At week 24, HbA1c decreased by -1.69% (95% CI -1.91 to -1.47) with Efsubaglutide Alfa 1 mg versus -0.74% (-0.96 to -0.52) with placebo, a placebo-corrected difference of -0.95% (95% CI -1.25 to -0.65; p < 0.0001).
Fasting plasma glucose (FPG)Efsubaglutide Alfa 1 mg vs placebofavours the comparator · t2dfeeds one cell of the map
Δ 1.59p < 0.001
FPG decreased by -2.09 mmol/L versus -0.50 mmol/L with placebo (difference - 1.59 mmol/L; p < 0.001).

clause the extractor read what became the number

2 · Its place on the map

Where it lands on the map

Rows are treatments, columns are outcomes. The coloured squares are the cells this paper feeds, coloured by the vote it casts there. Click one to jump to what this paper adds to it.

supports the treatmentfavours the comparatorno clear differenceread, but no usable result
3 · What it changes

What it adds to each cell

For every cell the paper feeds: the belief in the claim with and without this paper, and this paper's estimate drawn against every other readable study in the cell. The ringed dot is this paper.

Investigational compounds×glycemic control

InconclusiveOpen on the map →What to test next →

21 readable studies in this cell: 11 favour the treatment, 8 find no difference, 2 favour the comparator.

Belief with this paper
0.78replicated · 14 families support, 4 contradict · against placebo
Without it
0.78This paper does not move the number.
← favours the treatmentfavours the comparator →
0 · no effect
This paper · 2025
decrease -1.69-1.91 to -1.47
NCT004798822,414 enrolled · 2007
Δ -0.20-0.90 to 0.50
NCT002899002,340 enrolled · 2006
Δ 0.10-0.30 to 0.90
NCT03214380933 enrolled · 2017
Δ 0.06-0.05 to 0.16
NCT03235050834 enrolled · 2017
Δ -0.83-1.06 to -0.59
NCT00767000813 enrolled · 2008
Δ -0.51-0.80 to -0.22
NCT02119819420 enrolled · 2014
Δ -0.78-1.05 to -0.52
NCT04153929413 enrolled · 2020
Δ -1.53-1.84 to -1.22
NCT05048719383 enrolled · 2021
Δ -0.77-1.13 to -0.40
NCT00479466342 enrolled · 2007
Δ -30.6-44.0 to -17.3
NCT02973321296 enrolled · 2016
Δ -0.96-1.36 to -0.55
NCT04867785281 enrolled · 2021
Δ -0.38-0.94 to 0.18
NCT02492763176 enrolled · 2015
Δ -0.39-0.88 to 0.11

Investigational compounds×body weight & composition

InconclusiveOpen on the map →What to test next →

12 readable studies in this cell: 8 favour the treatment, 3 find no difference, 1 favour the comparator.

Belief with this paper
1.00established · 9 families support, 0 contradict · against placebo
Without it
1.00This paper does not move the number.
← favours the treatmentfavours the comparator →
0 · no effect
This paper · 2025
Δ -0.72
NCT03235050834 enrolled · 2017
Δ -2.00-3.08 to -0.91
NCT05616013507 enrolled · 2022
Δ -14.5-18.0 to -11.0
NCT03486392474 enrolled · 2018
Δ -6.75-9.31 to -4.19
NCT04153929413 enrolled · 2020
Δ -7.68-9.52 to -5.83
NCT02973321296 enrolled · 2016
Δ -3.57-5.31 to -1.83
NCT04867785281 enrolled · 2021
Δ -0.49-2.07 to 1.08
NCT02492763176 enrolled · 2015
Δ -0.70-2.00 to 0.60
decrease -24.2
4 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

5 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

6 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

7 · Who and what money

Authors and funding

6 authors.

Weiping JiaDepartment of Endocrinology and Metabolism, Shanghai Jiao Tong University School of Medicine Affiliated Sixth People's Hospital, Shanghai Clinical Center for Diabetes, Shanghai Diabetes Institute, Shanghai Key Laboratory of Diabetes Mellitus, Shanghai, China.ORCID 0000-0002-6244-2168
Fan JiangInnogen Pharmaceutical Technology Co., Ltd., Shanghai, China.
Yulong XuInnogen Pharmaceutical Technology Co., Ltd., Shanghai, China.
Yiming LiDepartment of Endocrinology and Metabolism, Huashan Hospital, Shanghai Medical School, Fudan University, Shanghai, China.
Yuqian BaoDepartment of Endocrinology and Metabolism, Shanghai Jiao Tong University School of Medicine Affiliated Sixth People's Hospital, Shanghai Clinical Center for Diabetes, Shanghai Diabetes Institute, Shanghai Key Laboratory of Diabetes Mellitus, Shanghai, China.ORCID 0000-0002-4754-3470
Qinghua WangInnogen Pharmaceutical Technology Co., Ltd., Shanghai, China.ORCID 0000-0002-6478-0988

Funding

Innogen Pharmaceutical Co. Ltd., Shanghai, China
8 · The paper itself

Abstract

The marked sentences are the ones the graph read a number from.

aimsEfsubaglutide Alfa is a novel, long-acting, once-weekly GLP-1 receptor agonist. In the pivotal phase 2b/3 SUPER2 trial, Efsubaglutide Alfa 3 mg plus metformin showed significant efficacy and favourable safety in patients with type 2 diabetes (T2D) inadequately controlled on metformin. This post-hoc analysis evaluated the 1 mg dose. MATERIALS AND

methodsIn phase 2b, patients with T2D on metformin were randomized (1:1:1) to once-weekly Efsubaglutide Alfa 1 mg, 3 mg, or placebo for 12 weeks. After interim analysis, 3 mg was selected as the phase 3 dose. However, 155 patients already randomized (the "overrun" cohort) completed 24 weeks of double-blind treatment with 1 mg, then entered 28 weeks of open-label 3 mg and 4 weeks of follow-up. This analysis focused on the 1 mg cohort. The primary endpoint was change in HbA1c at week 24; secondary endpoints included fasting plasma glucose (FPG), body weight, HbA1c <7.0%, and subgroup analyses.

resultsAt week 24, HbA1c decreased by -1.69% (95% CI -1.91 to -1.47) with Efsubaglutide Alfa 1 mg versus -0.74% (-0.96 to -0.52) with placebo, a placebo-corrected difference of -0.95% (95% CI -1.25 to -0.65; p < 0.0001). FPG decreased by -2.09 mmol/L versus -0.50 mmol/L with placebo (difference - 1.59 mmol/L; p < 0.001). Body weight reduction was modest and not significant (-2.8% vs. -1.3%; LSM -0.72 kg; p = 0.137). HbA1c <7.0% was achieved by 56.3% versus 11.1% with placebo (p < 0.0001; odds ratio 8.3). Gastrointestinal adverse events were most common, generally mild and transient, and no drug-related serious events occurred.

conclusionsEfsubaglutide Alfa 1 mg provided clinically meaningful glucose lowering with good tolerability but without significant weight loss. These results support a lower-dose strategy for elderly or frail patients, those with low BMI, or individuals sensitive to gastrointestinal effects, and as a possible lead-in step before escalation. Confirmatory trials are warranted to establish long-term outcomes.

Indexed as

Diabetes Mellitus, Type 2Glucagon-Like Peptide-1 Receptor AgonistsHypoglycemic AgentsAdultAgedBlood GlucoseDouble-Blind MethodDrug Administration ScheduleDrug Therapy, CombinationFemaleGlycated HemoglobinHumansMaleMetforminMiddle AgedTreatment OutcomeBlood GlucoseGlucagon-Like Peptide-1 Receptor AgonistsGlycated Hemoglobinhemoglobin A1c protein, humanHypoglycemic AgentsMetformindiabetesEfsubaglutide Alfaglucagon‐like peptide‐1 receptor agonistobesitypharmacodynamicssafetytolerability

Identifiers

PMID40977363

What Socratic holds

Texttitle and abstract
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.