Efpeglenatide
Long-acting GLP-1 agonist
Also HM11260C, LAPS-Exendin, LAPS-Exendin-4 analog, GLP-1, GLP1, GLP-1 agonist
- Evidence
- BSome human evidence
- FDA status
- In clinical trialsas of 2026-10-27
- Route
- Injection
- Studies cited
- 1 human0 animal or cell
A weekly injection that Sanofi dropped for diabetes and that Korea approved for weight loss in 2026. One trial of 4,076 people found fewer heart attacks and strokes.
Sold for
Efpeglenatide is discussed as a weekly GLP-1 drug with proven heart and kidney benefits that got shelved for business reasons.
Studies say
A single 4,076-patient outcomes trial showed cardiovascular and kidney benefit comparable to approved GLP-1 drugs, which is strong but orphaned evidence, hence B.
Why grade B. One large randomized, placebo-controlled cardiovascular outcomes trial, AMPLITUDE-O (n=4,076), showed a 27% reduction in major cardiovascular events in high-risk type 2 diabetes, and a prespecified analysis confirmed the effect regardless of SGLT2 inhibitor use. The evidence is of high quality but the drug was never approved for diabetes and no second outcomes trial exists, so it stays at B. 23
FDA. Not approved by the FDA. Efpeglenatide is a once-weekly GLP-1 receptor agonist developed by Hanmi Pharmaceutical; Sanofi licensed it, ran a phase 3 program in type 2 diabetes, and returned the rights in 2020 before any filing. South Korea's Ministry of Food and Drug Safety approved it on October 7, 2026 for chronic weight management in adults with obesity or overweight who do not have diabetes, and no US marketing application has been reported.
Written from 4 cited sources. Fact-checked 2026-10-27: 15 claims checked, 0 corrected. Last refreshed 2026-10-27. Not physician reviewed.
What this means for you
- What people take it for
- Controlling blood sugar in type 2 diabetes.
- Can a US doctor prescribe it?
- No, not in the US. It is not FDA approved, though Korea approved it for weight loss in 2026.
- Properly tested in people?
- Partly: some human trials, with gaps: one trial of 4,076 people, and no second trial.
Evidence checklist
- Randomised controlled trial AMPLITUDE-O placebo-controlled outcomes trialyes
- Human study over 100 people AMPLITUDE-O 4,076 adultsyes
- More than one research group One program by one sponsorno
- Clinical outcomes, not surrogate markers 27% fewer major cardiovascular eventsyes
- Human safety data beyond case reports Trial safety for about 1.8 yearsyes
Drawn from the cited studies below. A dash means the sources give no information.
What it is
Efpeglenatide is a long-acting GLP-1 receptor agonist. It is built on exendin-4. This is the lizard-venom peptide that gave rise to exenatide. A flexible PEG spacer links the peptide to a piece of a human antibody. This slows its clearance. One shot a week is enough. GLP-1 drugs come from two main lines. One is based on exendin (exenatide, lixisenatide and efpeglenatide). The other is based on human GLP-1 (liraglutide, semaglutide and dulaglutide). 1
Hanmi developed the molecule. It licensed it to Sanofi in 2015. Sanofi ran the AMPLITUDE phase 3 program. In 2020 it gave the rights back as it left diabetes research. South Korea's drug regulator approved it on October 7, 2026 for chronic weight management in adults with obesity or overweight who do not have diabetes. 4 The FDA has not approved it, and no US marketing application has been reported. 2
How it works
Like other GLP-1 receptor agonists, efpeglenatide raises insulin release when glucose is high. It suppresses glucagon. It slows gastric emptying. It cuts appetite. GLP-1 receptors also sit on heart, blood vessel and kidney tissue. Trials of this drug class show heart and kidney benefits. These are thought to come partly from direct effects on inflammation and blood pressure. Lower glucose and weight also play a part. 12
What human research shows
AMPLITUDE-O randomized 4,076 adults with type 2 diabetes. All had heart disease, or kidney disease plus another risk factor. They got weekly efpeglenatide at two doses or placebo. Researchers followed them for a median of 1.8 years. Major adverse cardiovascular events were death from heart causes, heart attack or stroke. They hit 7.0% of efpeglenatide patients. On placebo it was 9.2%. The hazard ratio was 0.73. A kidney outcome combined new macroalbuminuria and loss of kidney function. It fell by about a third, from 18.4% to 13.0%. 2
In the trial, 15% of participants were already on an SGLT2 inhibitor. So researchers could test whether the two drug classes add to each other. The Circulation analysis looked at this. Heart and kidney benefits were similar with or without SGLT2 therapy. This supports using the two classes together. 3
| Study | Model | Finding |
|---|---|---|
| AMPLITUDE-O | Humans, n=4,076, randomized double-blind placebo-controlled, median 1.8 years | Major cardiovascular events were reduced by 27% (hazard ratio 0.73) and a composite kidney outcome by about 32%. 2 |
| AMPLITUDE-O SGLT2 analysis | Humans, prespecified subgroup analysis of AMPLITUDE-O by baseline SGLT2 inhibitor use | Cardiovascular and kidney benefits were consistent whether or not patients were taking an SGLT2 inhibitor. 3 |
Safety
Side effects in AMPLITUDE-O matched the GLP-1 class. Nausea, diarrhea and vomiting were more common than with placebo. More participants on efpeglenatide stopped treatment because of gut problems. Serious adverse events were not significantly more frequent than placebo. Neither were severe hypoglycemia, pancreatitis or retinopathy events. No one collected safety data beyond two years. Sanofi stopped development. 2
Questions for your clinician
- Since efpeglenatide is not approved, which approved GLP-1 drug fits my situation?
- How long was safety followed, and what about longer use?
- Would my current diabetes medicines change the benefit?
Questions people ask
Is efpeglenatide FDA-approved?
No. It completed a phase 3 program. But Sanofi returned the rights to Hanmi in 2020, and no US application was filed. South Korea approved it on October 7, 2026 for weight management in adults without diabetes. 24
Did efpeglenatide work?
In the one large outcomes trial, yes. It cut heart events by about 27% and kidney events by about a third compared with placebo. The trial had 4,076 high-risk patients with type 2 diabetes. Sanofi stopped development for business reasons. The trial did not fail. 2
How does efpeglenatide differ from semaglutide or dulaglutide?
It is built from exendin-4, the lizard-derived peptide behind exenatide. It is not built from human GLP-1. Its heart benefit in AMPLITUDE-O was in the same range as in trials of those drugs. That was notable. Earlier exendin-based drugs had shown weaker heart effects. 12
Citations
- StatPearls: glucagon-like peptide-1 receptor agonists ncbi.nlm.nih.gov
- Gerstein 2021, NEJM: cardiovascular and renal outcomes with efpeglenatide in type 2 diabetes (AMPLITUDE-O) doi.org
- Lam 2021, Circulation: efpeglenatide and clinical outcomes with and without concomitant SGLT2 inhibitor use doi.org
- South Korea MFDS: efpeglenatide (Efe) approval notice, October 2026 mfds.go.kr