Supaglutide
Supaglutide, GLP-1 and IgG2 Fc fusion protein, approved as efsubaglutide alfa
Written by Aaron CuhaReviewed Sep 2026
Also known as: Efsubaglutide alfa, Efsubaglutide Alfa injection, rE4
Approved in China in January 2025 for type 2 diabetes, on the back of two adaptive phase 2b/3 trials in more than 700 adults. Nearly everything indexed under the name supaglutide is monkey and mouse work, because the clinical programme is indexed under efsubaglutide alfa.
Overview
This compound is the clearest example on this site of a drug being invisible for reasons that have nothing to do with its evidence.
Search PubMed for supaglutide and you get six records: insulin secretion in mouse and human islets, glucose control in diabetic mice, weight and brown fat markers in high fat diet mice, pharmacokinetics in rats and monkeys, glucose homeostasis in diabetic rhesus monkeys, and liver fat in monkeys with spontaneous steatohepatitis. A reasonable person would conclude this is a preclinical compound.
It is an approved medicine. China's National Medical Products Administration approved efsubaglutide alfa injection in January 2025 for glycaemic control in adults with type 2 diabetes, and it has been added to the national reimbursement list. The pivotal trials, SUPER1 and SUPER2, are published in Diabetologia and Nature Communications respectively. They are indexed under the nonproprietary name, which is not the name the preclinical papers use.
Structurally it is a fusion protein: human GLP-1 joined to the Fc fragment of human immunoglobulin G2, which is a different long-acting strategy from the fatty acid acylation used in semaglutide and liraglutide and closer in concept to dulaglutide.
The diabetes evidence is genuinely strong for its scope. The weight evidence is not: the obesity programme has reached phase 2a, with 50 participants, and the phase 2b/3 obesity trial existed only as a published protocol at the time of this review.
Mechanism of action
A recombinant fusion protein in which human GLP-1 is linked to the Fc fragment of human immunoglobulin G2. The Fc domain confers a long circulating half-life through neonatal Fc receptor recycling, the same mechanism dulaglutide uses, rather than through albumin binding by a fatty acid side chain. Receptor activity is that of native GLP-1: glucose-dependent insulin secretion, glucagon suppression, delayed gastric emptying and reduced food intake. The published trials report improvements in beta cell functional measures alongside the glycaemic effect. Because it is a large fusion protein rather than a modified peptide, immunogenicity is a relevant question for it in a way it is not for small acylated analogues, and a 40 week repeat-dose toxicity study in cynomolgus monkeys examining toxicokinetics and immunogenicity has been published separately.
Human evidence
Two adaptive phase 2b/3 trials in type 2 diabetes totalling more than 700 randomised adults, which supported approval in China in January 2025. The obesity programme has reached phase 2a with 50 participants.
- SUPER1, drug-naive type 2 diabetes: glycated haemoglobin fell 2.15 percentage points on 3 mg weekly at 24 weeks, a difference of 1.68 points against placebo, with 68 percent reaching below 7.0 percent.
- SUPER2, added to metformin: glycated haemoglobin fell 1.80 percentage points against 0.74 on placebo at 24 weeks, followed by a 28 week open-label extension.
- Weight loss in the diabetes trials was modest, 3.14 percent on the 3 mg dose in SUPER1, which is the dose that was approved.
- LIGHT 1, phase 2a in obesity, 50 participants: 7.16 percent weight loss against 0.86 percent on placebo, with 2.00 kg of the loss being lean mass.
- Supporting human pharmacology is published separately: a phase 1 dose escalation, population pharmacokinetics, exposure-response analyses, a drug interaction study with metformin and digoxin, and a randomised trial of biweekly dosing.
What this does not tell you: The whole clinical programme was run in China by one sponsor whose founder is the corresponding author on both pivotal trials. There is no cardiovascular outcome trial, no trial in a non-Chinese population, and no head to head against semaglutide, tirzepatide or any other marketed incretin. The obesity claim rests on 50 people for four weeks at target dose. And the largest published safety exposure beyond the trials is a 40 week toxicity study in monkeys, not a long-term human safety database.
Reading the research record
The gap between this compound's evidence and its visibility is the point of this batch.
By the standard this site applies to Western programmes, the diabetes case here is solid: two randomised, double-blind, placebo-controlled adaptive trials, one drug-naive and one on metformin background, both with prespecified phase 3 stages, both published in journals with real peer review, both reporting effect sizes in the range you would expect from a weekly GLP-1 agonist. That is more and better human evidence than most compounds documented on this site have.
It is also invisible in English. The reason is naming. The preclinical work says supaglutide. The trials say efsubaglutide alfa. The Chinese market says something else again. Nothing connects them in a search.
The honest reading is therefore split. For type 2 diabetes this is an approved drug with published pivotal trials. For weight loss it is a 50 person phase 2a signal with a published protocol for the larger trial, and any claim that it is an obesity drug is ahead of the data.
A note on what Chinese approval does and does not tell you. China's National Medical Products Administration requires trials in Chinese patients, and the pivotal trials behind these approvals are real randomised controlled trials published in mainstream journals, several of them in Diabetologia, Nature Communications, Diabetes Obesity and Metabolism and the Lancet regional title. What is usually missing compared with the Western incretin programmes is a cardiovascular outcome trial. Semaglutide and liraglutide carry cardiovascular outcome data in tens of thousands of patients followed for years; none of the compounds on this page does. So the correct statement is that these drugs are shown to lower glycated haemoglobin and body weight in Chinese adults over months, not that they are shown to prevent heart attacks. That gap is a real difference in the evidence, and it is separate from the question of whether a Western reader has heard of the drug.
The evidence, charted
Fig. 1 · evidence composition
3of 5 citations (60%) are in people
Counted from the citation list on this page. The Human count is the same number shown in the badge at the top. Both understate any literature larger than the sources we cite.
Fig. 2 · evidence over time
Evidence spans 3 distinct years, 2021 to 2026, counted from the citation list on this page.
Fig. 3 · legal status at a glance
US
Not approved
UK
Not approved
AU
Not approved
CA
Not approved
Not approved in any of the four jurisdictions shown. A jurisdiction's classification is a regulatory fact, not a verdict on the science; see Legal status below for the full text and any notes.
Fig. 4 · dose response
No human dose response curve exists
We draw this figure where the data supports it. For this compound in humans it does not, so the panel stays empty rather than borrowing an animal curve and implying it transfers.
Key studies & citations
- Human2026
Efficacy and safety of efsubaglutide alfa in individuals with type 2 diabetes (SUPER1): a randomised, double-blind, placebo-controlled, Phase IIb/III trial
Two-stage seamless adaptive trial in drug-naive adults with newly diagnosed type 2 diabetes. Phase 2b randomised 140 participants across 1, 2 and 3 mg weekly and placebo; phase 3 randomised a further 297 to 1 mg, 3 mg or placebo. At week 24 glycated haemoglobin fell 1.73 percentage points on 1 mg and 2.15 on 3 mg, with treatment differences against placebo of 1.26 and 1.68 percentage points. 56 percent and 68 percent reached a glycated haemoglobin below 7.0 percent. Body weight fell 0.97 percent on 1 mg and 3.14 percent on 3 mg, and only the 3 mg weight difference against placebo was significant. Sponsored by Innogen Pharmaceutical; the corresponding author is the company's founder.
Diabetologia - Human2026
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)
The add-on to metformin trial. Phase 2b randomised to 1 mg, 3 mg or placebo for 12 weeks, at which point glycated haemoglobin had fallen 1.10 and 1.43 percentage points. Phase 3 randomised new participants to 3 mg or placebo for 24 weeks of double-blind treatment followed by a 28 week open-label extension; glycated haemoglobin fell 1.80 percentage points against 0.74 on placebo, an estimated treatment difference of 1.06 points. Adverse events were predominantly mild to moderate gastrointestinal events. Same sponsor and same founder as SUPER1.
Nature Communications - Human2026
Efficacy, tolerability, and safety of Efsubaglutide Alfa in participants with obesity or overweight (LIGHT 1): A randomized, double-blind, placebo-controlled, ascending-dose phase 2a trial
The entire published obesity efficacy record: 50 participants across five dose cohorts and placebo, mean baseline weight 92.9 kg. Mean weight reduction was 7.16 percent against 0.86 percent on placebo, and 82.5 percent of treated participants lost at least 5 percent against none on placebo. Fat mass fell 4.47 kg and lean mass also fell 2.00 kg. This is a 50 person dose-ranging study, not an obesity efficacy trial, and the compound is not approved for weight management.
Diabetes, Obesity and Metabolism - Animal2021
Novel GLP-1 analog supaglutide improves glucose homeostasis in diabetic monkeys
Diabetic rhesus monkeys. A single subcutaneous injection transiently reduced blood glucose dose-dependently; over four weeks of weekly dosing fasting and random glucose fell dose-dependently with declining plasma fructosamine, body weight decreased alongside reduced food intake, glucose tolerance improved and glucose-stimulated insulin secretion increased. A monkey study, indexed under the development name, and one of the reasons a search on supaglutide makes an approved medicine look preclinical.
Journal of Endocrinology - Animal2024
Supaglutide alleviates hepatic steatosis in monkeys with spontaneous MASH
Fifteen rhesus monkeys with biopsy-confirmed metabolic dysfunction-associated steatohepatitis, given weekly subcutaneous supaglutide at 50 or 150 micrograms per kg or placebo for three months. Liver fat measured by MRI proton density fat fraction fell 40 percent from baseline against placebo, and histological steatosis improved without worsening of fibrosis on ultrasound-guided biopsy. Fifteen monkeys, three months, no human liver endpoint has been tested.
Diabetology and Metabolic Syndrome
Frequently asked questions
Is supaglutide approved?
Yes, in China. The National Medical Products Administration approved efsubaglutide alfa injection in January 2025 for glycaemic control in adults with type 2 diabetes, and it is on China's national reimbursement list. It is not approved in the United States, United Kingdom, Australia or Canada, and it is not approved for weight management anywhere.
Why does it look like a preclinical compound when I search for it?
Because the six PubMed records under the name supaglutide are mouse, rat and monkey studies, while the human trials are indexed under the nonproprietary name efsubaglutide alfa. The same molecule has two literatures that do not cross-reference each other.
How much weight does it cause people to lose?
In the approved diabetes dose, 3 mg weekly, body weight fell 3.14 percent over 24 weeks in the pivotal drug-naive trial. In a separate 50 person phase 2a study in people with obesity, using doses from 5 to 20 mg, mean weight loss was 7.16 percent against 0.86 percent on placebo, with 2.00 kg of the loss coming from lean mass. That is dose-ranging data, not an obesity efficacy result.
How is it different from semaglutide?
Structurally. Semaglutide is a modified peptide with a fatty acid side chain that binds albumin to extend its half-life. This is a fusion protein, human GLP-1 joined to an immunoglobulin G2 Fc fragment, which extends half-life through Fc receptor recycling instead, the same approach dulaglutide uses. No trial has compared the two directly.
Does it help fatty liver?
There is a monkey study. Fifteen rhesus monkeys with biopsy-confirmed steatohepatitis showed a 40 percent reduction in liver fat on MRI over three months without worsening fibrosis, and a separate mouse study reports improvement in fibrosis features. No human liver endpoint has been tested.