Amycretin vs Efpeglenatide
Comprehensive side-by-side comparison of mechanisms, dosing, side effects, and research
Also: Zenagamtide, NNC0487-0111
Amycretin is Novo Nordisk's single-molecule agonist of both the GLP-1 and amylin receptors, developed as a once-weekly injection and a once-daily pill. Early trials produced some of the biggest weight-loss numbers seen with any obesity drug so far, and the injectable version entered phase 3 (the AMAZE program) in 2026. It is not approved anywhere, and everything known about it comes from company-run trials of up to 36 weeks.
Also: Eppe, HM11260C
Efpeglenatide is a long-acting, once-weekly GLP-1 agonist from Hanmi Pharmaceutical, made by linking an exendin-4 analog to an antibody fragment so it lasts days instead of hours. Sanofi licensed it for diabetes in 2015 and handed it back in 2020 despite a positive heart outcomes trial. Hanmi relaunched it for obesity, and on 7 October 2026 South Korea approved it as Eppe, the country's first homegrown GLP-1 obesity drug. It is not approved by the FDA or EMA.
Key Comparison Insights
- Both peptides belong to the Weight Loss category, suggesting similar primary applications.
Detailed Comparison
| Attribute | Amycretin | Efpeglenatide |
|---|---|---|
| Category | Weight Loss | Weight Loss |
| FDA Status | Not FDA Approved | Not FDA Approved |
| Clinical Status | Pre I II III IV FDA | Pre I II III IV FDA |
| Mechanism of Action | Amycretin hits two appetite systems at once. The GLP-1 side slows stomach emptying, boosts insulin release after meals, and dampens appetite in the brain, the same biology behind semaglutide. The amylin side mimics a hormone your pancreas releases alongside insulin, which acts on the brainstem to make you feel full sooner and also curbs glucagon after eating. Novo combined these two signals in one molecule rather than mixing two drugs (which is what its CagriSema combination does). The bet is that the two pathways add together, giving more weight loss than either alone. That idea fits the early data, but it has not yet been tested head-to-head against semaglutide or tirzepatide in a large trial. | Efpeglenatide activates the GLP-1 receptor, which raises insulin release after meals, lowers glucagon, slows stomach emptying and reduces appetite. The active part is an exendin-4 analog (the same parent peptide as exenatide and lixisenatide) attached through a small linker to a human IgG4 Fc fragment, using Hanmi's LAPSCOVERY platform. The Fc piece makes the molecule big enough to dodge kidney clearance and lets it recycle in the body, which stretches its half-life to weekly dosing. Hanmi argues its lower brain penetration explains the milder GI profile; that is a company argument rather than an independently proven fact. |
| Common Dosing | Trial doses of 1.25-40 mg once weekly (injection) Once weekly (injection) or once daily (tablet) | 10 mg once weekly maintenance (Korean label) Once weekly |
| Administration | Subcutaneous injection once weekly, or oral tablet once daily (separate formulations) | Subcutaneous auto-injector once weekly |
| Typical Duration | 20-36 weeks in published trials; phase 3 runs longer | Long-term (chronic weight management); 40-64 weeks in the Korean phase 3 |
| Best Time to Take | Same day each week (injection); trial protocols set timing for the tablet | Same day each week |
Possible Side Effects May vary by individual |
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| Research Summary | Two early trials were published in The Lancet in June 2025. In the subcutaneous phase 1b/2a trial (125 adults with overweight or obesity), the estimated weight loss assuming full adherence was 24.3% at 60 mg over 36 weeks and 22.0% at 20 mg over 36 weeks, versus roughly flat weight on placebo, with no plateau by the end of treatment. A separate phase 1 trial of the oral tablet (144 people, 12 weeks) showed up to 13.1% loss at the highest dose. In November 2025 Novo reported a 36-week phase 2 trial in 448 adults with type 2 diabetes: up to 14.5% weight loss with weekly injections (2.6% on placebo), up to 10.1% with the daily pill, and HbA1c drops of up to 1.8 points. Side effects were mostly gastrointestinal, dose-related, and mild to moderate. Novo moved both forms into phase 3; AMAZE 1 (weekly injection at 1.25, 5, 20 or 40 mg versus placebo, about 1,150 people without diabetes) is registered as NCT07339423 with completion expected in 2029. Honest caveats: the headline numbers come from small trials using an efficacy estimand that assumes everyone stayed on drug, and long-term safety is unknown. | The strongest data come from Sanofi's AMPLITUDE-O trial (NEJM 2021), which enrolled people with type 2 diabetes and cardiovascular or kidney disease. Efpeglenatide 4 or 6 mg weekly cut major cardiovascular events by 27% versus placebo (7.0% vs 9.2%, hazard ratio 0.73) over a median of 1.8 years, and also reduced kidney outcomes. Sanofi still returned the rights in 2020 for business reasons. Hanmi then ran a Korean phase 3 obesity trial in 448 adults without diabetes (average BMI 32): at 40 weeks, weight loss was 9.02% versus 0.89% on placebo, and 75.1% lost at least 5%. That is less weight loss than semaglutide or tirzepatide in their pivotal trials, though trial designs differ, and GI side effects were somewhat lower (diarrhea 17.6%, nausea 16.6%, vomiting 11.6%). Korea's MFDS approved it for chronic weight management on 7 October 2026, with launch planned for late October. Bottom line: a solid, proven drug class member with real outcome data, but modest weight loss and no Western approval. |
Frequently Asked Questions: Amycretin vs Efpeglenatide
What is the difference between Amycretin and Efpeglenatide?
Amycretin is a weight loss peptide that amycretin is novo nordisk's single-molecule agonist of both the glp-1 and amylin receptors, developed as a once-weekly injection and a once-daily pill. early trials produced some of the biggest weight-loss numbers seen with any obesity drug so far, and the injectable version entered phase 3 (the amaze program) in 2026. it is not approved anywhere, and everything known about it comes from company-run trials of up to 36 weeks. Efpeglenatide is a weight loss peptide that efpeglenatide is a long-acting, once-weekly glp-1 agonist from hanmi pharmaceutical, made by linking an exendin-4 analog to an antibody fragment so it lasts days instead of hours. sanofi licensed it for diabetes in 2015 and handed it back in 2020 despite a positive heart outcomes trial. hanmi relaunched it for obesity, and on 7 october 2026 south korea approved it as eppe, the country's first homegrown glp-1 obesity drug. it is not approved by the fda or ema. The main differences lie in their mechanisms of action and clinical applications.
Which is better, Amycretin or Efpeglenatide?
Neither is universally "better" - the choice depends on your specific goals. Amycretin is typically used for weight loss purposes, while Efpeglenatide is used for weight loss. Always consult with a healthcare provider to determine which may be appropriate for your situation.
Can Amycretin and Efpeglenatide be used together?
Some peptide protocols combine multiple compounds for synergistic effects. However, using Amycretin and Efpeglenatide together should only be considered under medical supervision, as both compounds have their own side effect profiles and potential interactions. Research on their combined use may be limited.