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Type2 DiabetesPhase 2/3NCT04998032

A Study of Efficacy and Safety of Supaglutide in Type 2 Diabetes Patients On Metformin Treatment(SUPER-2)

A Phase 2/3 study testing supaglutide injection+metformin in people with Type2 Diabetes, run by Shanghai Yinnuo Pharmaceutical Technology Co., Ltd. at 61 sites in China.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

This is a study to evaluate the efficacy and safety of Supaglutide injection in the treatment of type 2 diabetes patients with poor glycemic control after metformin treatment. This trial includes dosage determination (Phase IIb) and efficacy confirmation stage(Phase III ). Read more about this study

Who is it for?
Ages 18 to 75 years
Conditions the study is for
Type2 Diabetes
What is being tested?
supaglutide injection+metformin
Type of treatment
Injection or infusion
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
620 participants
Where
61 sitesChina
Study dates
12 Oct 2021to 13 Aug 2023
Phase
Phase 2/3
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 75 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Male or female patients aged from 18 to 75;
  • Clinical diagnosed of Type 2 diabetes for at least 8 weeks ，receive metformin single treatment ；
  • During screening, HbA1c: 7.5% ≤ HbA1c ≤ 11% ，and before randomization 7.5% ≤ HbA1c ≤ 10.5%;
  • During screening and before randomization: FPG< 13.9 mmol/L； 5.18.5 kg/m2 ≤ BMI ≤ 35 kg/m2;
  • 6. without birth plan and voluntarily take effective contraceptive measures; 7. fully understood the study, signed the informed consent；

Who cannot join

  • Diabetes other than Type 2;
  • Any dipeptidyl peptidase IV and / or glucagon-like peptide-1 （GLP-1）analogues were used within 3 months before screening;
  • Continuous use of insulin for more than 14 days in the previous year;
  • C-Peptide <0.3 nmol/L;
  • Diabetic ketoacidosis, diabetic lactic acidosis or hyperosmolar non ketonic diabetic coma occurred within 6 months before screening;
  • Unstable proliferative retinopathy or macular lesion, severe diabetic neuropathy, intermittent claudication or diabetic foot occurred within 6 months before screening;
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  • Severe hypoglycemia occurred within 6 months before screening
  • Severe trauma infection or operation within one month before screening;
  • Blood donation or massive blood loss or transfusion within 3 months ;
  • Suspected active infection ;
  • Growth hormone therapy was performed within 6 months before screening;
  • Patients having received corticosteroid continuous ≥ 7 days through within 2 months ;
  • use any drugs or surgery with weight control effect within 2 months;
  • weight change of more than 5% within 3 months;
  • mean systolic pressure (SBP) ≥ 160mmhg and / or diastolic pressure （DBP） ≥ 90 mmHg at screening, or new/changed antihypertensive drugs or adjusted dosage of antihypertensive drugs within 4 weeks before screening or before induction period
  • with a history of severe cardiovascular disease, high risk of stroke/stroke within 6 months before screening;
  • with a history of acute or chronic pancreatitis, symptomatic gallbladder , pancreatic injury and other risk factors for pancreatitis, or with blood amylase and/or blood lipase ≥1.5 times the upper limit of normal (ULN) at the time of screening or before randomization;
  • Calcitonin level ≥50 ng/L (pg/mL) during screening;
  • with a history of medullary thyroid cancer, multiple endocrine neoplasm (Men) 2A or 2B syndrome, or related family history;
  • with clinically significant abnormal gastric emptying , severe chronic gastrointestinal diseases , long-term use of drugs that have a direct impact on gastrointestinal peristalsis , or having undergone gastrointestinal surgery within 6 months before screening, are not suitable to participate in this clinical study according to the evaluation of the researchers;
  • suffering from hematological diseases or any disease causing hemolysis or erythrocyte instability ;
  • Uncontrolled hyperthyroidism or hypothyroidism;
  • with hemoglobinopathy that may affect the determination of HbA1c levels;
  • HBsAg, Hepatitis C antibody, HIV-Ab, Treponema pallidum antibody or Corona Virus Disease 2019 nucleic acid tested positive;
  • serious mental illness;
  • drinking more than 14 standard units weekly within 6 months before screening ;
  • a history of organ transplantation or other acquired or congenital immune system diseases;
  • allergic to the active ingredients (GLP-1 and GLP-1 analogues) of the study drug;
  • clear contraindications for the use of metformin;
  • clear contraindications for Empagliflozin；
  • Any of the following conditions: the pacemaker was installed when screened; no pacemaker was installed, but 12 lead ECG showed degree II or III atrioventricular block, long QT syndrome or QTc interval ≥ 450ms ; Patients with New York Heart Function Classification III or IV; Or other abnormal cardiac function with clinical significance that is not suitable for clinical research judged by researchers;
  • acute or chronic hepatitis, or whose laboratory examination indexes meet one of the following criteria at the time of screening or before randomization : alanine aminotransferase (ALT) level ≥ 2.5 fold ULN, aspartate aminotransferase (AST) ≥ 2.5 fold ULN, fasting triglyceride (TG) > 5.7 mmol/L or 500 mg/dl; the glomerular filtration rate (EGFR) < 60 ml/min/1.73 square meters was calculated by CKD-EPI (epi - (SCR)) formula;
  • participated in clinical trials of other drugs or devices within 3 months before screening;
  • Medication compliance in the metformin dosage stable period was < 80% or > 120%;
  • Supaglutide placebo injection compliance during the induction period was <75% or>125%, or metformin compliance <80% or >120%;
  • Any other situation that researchers think may affect the patients' informed consent or compliance with the trial protocol;

Trial locations and contacts

61 sites in 1 country.

61 sites in 1 country

China61 sites

  • Beijing Boai Hospital

    Beijing

  • Beijing Pinggu Hospital

    Beijing

  • Emergency General Hospital

    Beijing

  • Cangzhou Central Hospital

    Cangzhou

  • Cangzhou Hospital of Integrated TCM-WM Hebei

    Cangzhou

  • The Second Hospital of Jilin University

    Changchun

  • First People's Hospital of Changde

    Changde

  • Changsha Hopital Affiliated to Hunan University

    Changsha

  • The Fourth Hospital of Changsha

    Changsha

  • Chengdu Fifth People's Hospital

    Chengdu

  • Chenzhou First People's Hospital

    Chenzhou

  • Chongqing Ninth People's Hospital

    Chongqing

  • Dalian Municipal Central Hospital

    Dalian

  • Daqing People's Hospital

    Daqing

  • Jilin Guowen Hospital

    Gongzhuling

  • Handan First Hospital

    Handan

  • The Fourth Affiliated Hospital of Harbin Medical University

    Harbin

  • Heze Municipal Hospital

    Heze

  • Huai'an First People's Hospital

    Huai'an

  • Huai'an Second People's Hospital

    Huai'an

  • Huizhou Central Hospital

    Huizhou

  • Jilin People's Hospital

    Jilin City

  • Jinan Central Hospital Affiliated to Shandong First Medical University

    Jinan

  • Jincheng General Hospital

    Jincheng

  • Jingzhou Central Hospital

    Jingzhou

  • The Second Affiliated Hospital of Kunming Medical University

    Kunming

  • The Second People's Hospital of Lianyungang

    Lianyungang

  • Linfen People's Hospital

    Linfen

  • First People's Hospital of Tancheng

    Linyi

  • Liuzhou People's Hospital

    Liuzhou

  • The First Affiliated Hospital of Henan University

    Luoyang

  • Meihekou Central Hospital

    Meihekou

  • Jiangxi Provincial People's Hospital

    Nanchang

  • Nanjing First Hospital

    Nanjing

  • Nanjing Jiangning Hospital

    Nanjing

  • Sir Run Run Hospital of Nanjing Medical University

    Nanjing

  • Nanyang First People's Hospital

    Nanyang

  • Nanyang Second General Hospital

    Nanyang

  • The First Affiliated Hospital of Nanyang Medical College

    Nanyang

  • Puyang Oilfield General Hospital

    Pujiang

  • The First Hospital of Qinhuangdao

    Qinhuangdao

  • The First Hospital of Qiqihar

    Qiqihar

  • Changhai Hospital

    Shanghai

  • Huadong Hospital

    Shanghai

  • Shanghai Pudong New Area People's Hospital

    Shanghai

  • Shanghai Sixth People's Hospital Affiliated to Shanghai JiaoTong University

    Shanghai

  • Shanghai Tongren Hospital

    Shanghai

  • Siping Central Hospital

    Siping

  • Second Hospital of Shanxi Medical University

    Taiyuan

  • The Second Affiliated Hospital of Shandong First Medical University

    Tanan

  • The Second Hospital of Tanjin Medical University

    Tianjin

  • Tianjin Medical University General Hospital

    Tianjing

  • Union Hospital of Tongji Medical College, Huazhong University of Science and Technology

    Wuhan

  • Jiangyin People's Hospital

    Wuxi

  • The Affiliated Hospital of Xuzhou Medical University

    Xuzhou

  • Xuzhou Cancer Hospital

    Xuzhou

  • The Second People's Hospital of Yibin

    Yibin

  • Yichun People's Hospital

    Yichun

  • Yiyang Central Hospital

    Yiyang

  • The Second Affiliated Hospital of Zhengzhou University

    Zhengzhou

  • First People's Hospital of Zunyi

    Zunyi

Other trials in China

About this study

Official title: Efficacy and Safety of Once-weekly Supaglutide Versus Placebo in Patients With Type 2 Diabetes Suboptimally Controlled on Metformin: A Multicenter, Randomized, Double-blind, Placebo-controlled Clinical Trial

This is a study to evaluate the efficacy and safety of Supaglutide injection in the treatment of type 2 diabetes patients with poor glycemic control after metformin treatment.

This trial includes dosage determination (Phase IIb) and efficacy confirmation stage(Phase III ). The primary outcome of the phase IIb period is to preliminarily evaluate the efficacy and safety of Supaglutide combined with metformin and to provide the recommended dosage for the Phase 3 period after 12-week treatment.

The primary outcome of the Phase III period is to evaluate the efficacy and safety of Supaglutide combined with metformin treatment after 24-week, double-blind treatment. The secondary outcome is to evaluate the efficacy and safety of Supaglutide combined with metformin during the 24-week, double-blinded plus 28-week, open-label treatment period.

Read the detailed description

This trial includes a 2-week screening period, a 4-week metformin titration and dose-stabilization period, a 4-week induction period, a 24-week double-blind treatment period and a 28-week open-label treatment period, followed by a 4-week follow-up period and a follow-up visit. We calculated that the sample size would need to be 632, including 120 subjects in the period of Phase IIb and 512 subjects in the period of Phase III. During the phase IIb period, subjects were randomly assigned to once-weekly subcutaneously injected Supaglutide 1mg plus metformin, 3mg plus metformin and placebo plus metformin at a ratio of 1:1:1.

When the number of participants who have completed the 12-week follow up reached 120, interim analyses will be performed and the results will be evaluated by Independent Data Monitoring Committee experts to determine the recommended phase 3 dosage.

During the phase III stage, subjects were randomly assigned 1:1 to the "recommended phase 3 dosage + metformin" group and the "placebo + metformin" group.

Conditions
Type2 Diabetes
Being tested
supaglutide injection+metformin, placebo+metformin

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • supaglutide injection+metforminBiological

    supaglutide subcutaneous injection under RP3D dose combined with metformin treatment

  • placebo+metforminOther

    placebo subcutaneous injection combined with metformin treatment

Study groups in NCT04998032
Study groupRoleWhat they receive
supaglutide RP3D dose+metforminExperimentalSupaglutide Subcutaneous injection once a week for 52weeks,combined with metformin
Receives: Biological: supaglutide injection+metformin
placebo+metforminPlacebo comparatorPlacebo Subcutaneous injection once a week for 52weeks,,combined with metformin
Receives: Other: placebo+metformin

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. HbA1c

    The change in mean HbA1c concentrations (%)from baseline with Supaglutide versus placebo

    Measured: 12 weeks for phase IIb; 24weeks and 52 weeks for phase III

Secondary outcomes (14)

  1. fasting plasma glucose

    Changes in fasting plasma glucose (mmol/L) relative to baseline

    Measured: 12 weeks for phase IIb; 24weeks and 52 weeks for phase III

  2. HbA1c<7.0% and <6.5%

    The proportion of participants who achieved HbA1c target (HbA1c<7.0% and <6.5% Patient percentage)

    Measured: 12 weeks for phase IIb; 24weeks and 52 weeks for phase III

  3. Fasting insulin

    Fasting insulin changes（pmol/L) relative to baseline

    Measured: 12 weeks for phase IIb; 24weeks and 52 weeks for phase III

  4. fasting C-peptide

    Fasting C-peptide changes (nmol/L) relative to baseline

    Measured: 12 weeks for phase IIb; 24weeks and 52 weeks for phase III

  5. fasting glucagon

    fasting glucagon changes (pg/ml) relative to baseline

    Measured: 12 weeks for phase IIb; 24weeks and 52 weeks for phase III

  6. Area under the curve of blood glucose

    Area under the curve of blood glucose (AUC0-120min,mmol/L) during the multi-maneuvering target tracking

    Measured: 12 weeks for phase IIb; 24weeks and 52 weeks for phase III

  7. Area under the curve of insulin

    Area under the curve of insulin (AUC0-120min,pmol/L) during the MMTT

    Measured: 12 weeks for phase IIb; 24weeks and 52 weeks for phase III

  8. Area under the curve of C-peptide

    Area under the curve of C-peptide (AUC0-120min,nmol/L) during the MMTT

    Measured: 12 weeks for phase IIb; 24weeks and 52 weeks for phase III

  9. Total cholesterol

    Changes in total cholesterol (mmol/L) relative to baseline

    Measured: 12 weeks for phase IIb; 24weeks and 52 weeks for phase III

  10. low density lipoprotein

    Changes in low density lipoprotein (mmol/L) relative to baseline

    Measured: 12 weeks for phase IIb; 24weeks and 52 weeks for phase III

  11. High density lipoprotein

    Changes in high density lipoprotein (mmol/L) relative to baseline

    Measured: 12 weeks for phase IIb; 24weeks and 52 weeks for phase III

  12. triglyceride

    Changes in triglyceride(mmol/L) relative to baseline

    Measured: 12 weeks for phase IIb; 24weeks and 52 weeks for phase III

  13. weight

    Weight change from baseline(kg)

    Measured: 12 weeks for phase IIb; 24weeks and 52 weeks for phase III

  14. salvage treatment

    Percentage of subjects receiving salvage treatment(%)

    Measured: 12 weeks for phase IIb; 24weeks and 52 weeks for phase III

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted10 Aug 2021
  2. Study start12 Oct 2021
  3. Primary completion15 Jun 2023
  4. Study completion13 Aug 2023

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2/3
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Model description
This clinical trial includes dosage determination (Phase IIb) and efficacy confirmation stage(Phase III ). During the phase IIb, subjects were randomly assigned to Supaglutide 1mg + metformin, Supaglutide 3mg + metformin and placebo + metformin according to a 1:1:1 ratio. When 120 subjects complete the 12 weeks of follow-up, Interim analysis will be performed and the results be evaluated by IDMC to confirm the RP3D dose. And then during the phase III, subjects were randomly assigned to Supaglutide RP3D + metformin, placebo + metformin group according to a 1:1 ratio.
Masking
Double blind
Who is masked
Participant, Investigator
Enrolment
620 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04998032
Sponsor's protocol ID
YN011-302
Status last verified
Dec 2024
First submitted
28 Jul 2021
Last updated
6 Dec 2024
Results posted
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • Jia W, Gao F, Lu J, Cheng Z, Dong X, Shi X, Su X, Li L, Zhang W, Wang Y, Ma J, Li S, Wang H, Cheng L, Mao L, Jiang C, Li Q, Li X, Zheng X, Liu M, Sun J, Peng H, Pan H, Ling H, Jiang C, Song J, Zhang X, Zhang L, Liu Y, Zeng T, Zhao Y, Xu Y, Li Y, Bao Y, Zhou J, Wang Q. Efsubaglutide alfa added to metformin improves glycaemia with beta-cell functional responses in type 2 diabetes: a randomised, double-blind, placebo-controlled, two-stage adaptive phase 2b/3 trial (SUPER 2). Nat Commun. 2026 May 8;17(1):6222. doi: 10.1038/s41467-026-72574-7.

    PubMed 42103705

  • Wang Q, Jiang F, Xu Y, Lei Y, Zhang L, Sun X. Exposure-Response Analysis of Efsubaglutide Alfa in Patients with Type 2 Diabetes Treated with Metformin. Clin Pharmacokinet. 2025 Dec;64(12):1799-1809. doi: 10.1007/s40262-025-01569-2. Epub 2025 Sep 24.

    PubMed 40991141

  • Lou YR, Xu YL, Xiong Y, Deng C, Wang Q. Population Pharmacokinetics of Efsubaglutide Alfa in Healthy Subjects and Subjects with Type 2 Diabetes. Clin Pharmacokinet. 2025 Apr;64(4):533-552. doi: 10.1007/s40262-025-01475-7. Epub 2025 Feb 17.

    PubMed 39961992

Questions about this trial

What is this clinical trial studying?

A Phase 2/3 study testing supaglutide injection+metformin in people with Type2 Diabetes, run by Shanghai Yinnuo Pharmaceutical Technology Co., Ltd. at 61 sites in China.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 5 inclusion and 36 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 6 Dec 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 61 sites in China. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

HbA1c (time frame: 12 weeks for phase IIb; 24weeks and 52 weeks for phase III). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT04998032, which also lists 3 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Dec 2024.

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