Amycretin vs Retatrutide
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: LY3437943, Triple G
Retatrutide is the heavy hitter of the new weight-loss drugs: a once-weekly injectable peptide that hits three receptors at once - GIP, GLP-1, and glucagon - earning it the nickname triple-G agonist. In phase 2 it produced about 24 percent weight loss at the top dose, and in the phase 3 TRIUMPH-1 trial Lilly reported 28.3 percent at 12 mg over 80 weeks. It is investigational, made by Eli Lilly, and not FDA approved; Lilly plans to file with the FDA in the first quarter of 2027. Because it is not an approved drug, FDA says it cannot be legally compounded.
Key Comparison Insights
- Both peptides belong to the Weight Loss category, suggesting similar primary applications.
Detailed Comparison
| Attribute | Amycretin | Retatrutide |
|---|---|---|
| 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. | Retatrutide combines three hormone signals into one molecule. The GLP-1 component curbs appetite and slows stomach emptying, the GIP component supports insulin response and may improve how fat tissue handles nutrients, and the added glucagon receptor activity is the novel piece: glucagon can increase energy expenditure and fat burning in the liver. The idea is that two arms cut how much you eat while the third raises how much you burn, which is why retatrutide is thought to push weight loss further than GLP-1-only drugs like semaglutide or even the dual GIP/GLP-1 agonist tirzepatide. The exact contribution of each receptor in humans is still being worked out, so consider the glucagon-driven energy-expenditure story a strong hypothesis rather than fully nailed down. |
| Common Dosing | Trial doses of 1.25-40 mg once weekly (injection) Once weekly (injection) or once daily (tablet) | 4-12 mg weekly Once weekly, same day each week |
| Administration | Subcutaneous injection once weekly, or oral tablet once daily (separate formulations) | Subcutaneous injection weekly |
| Typical Duration | 20-36 weeks in published trials; phase 3 runs longer | Long-term use expected |
| Best Time to Take | Same day each week (injection); trial protocols set timing for the tablet | Morning, 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 first big human evidence was the phase 2 trial by Jastreboff and colleagues (New England Journal of Medicine, 2023), which randomized 338 adults with obesity (without type 2 diabetes) over 48 weeks. Mean weight reduction reached about 24 percent at the 12 mg dose, and weight loss had not clearly plateaued by week 48. In a liver-fat substudy of 98 participants, liver fat dropped by about 81 to 82 percent at the 8 and 12 mg doses by week 24. Phase 3 has since read out: in TRIUMPH-1, Lilly reported mean weight loss of 19.0, 25.9 and 28.3 percent at 4, 9 and 12 mg over 80 weeks versus 2.2 percent on placebo (efficacy estimand, which assumes people stayed on the drug; analyses counting everyone randomized come out a few points lower). TRIUMPH-2 (type 2 diabetes plus obesity) reached about 20.8 percent at 12 mg, and TRIUMPH-3 (severe obesity plus heart disease) about 22.6 percent. Side effects were dominated by dose-dependent gastrointestinal issues like nausea, vomiting, and diarrhea, plus a dysesthesia (skin sensitivity) signal at the top dose. Retatrutide sold outside of trials is not an approved, quality-controlled medicine. |
Frequently Asked Questions: Amycretin vs Retatrutide
What is the difference between Amycretin and Retatrutide?
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. Retatrutide is a weight loss peptide that retatrutide is the heavy hitter of the new weight-loss drugs: a once-weekly injectable peptide that hits three receptors at once - gip, glp-1, and glucagon - earning it the nickname triple-g agonist. in phase 2 it produced about 24 percent weight loss at the top dose, and in the phase 3 triumph-1 trial lilly reported 28.3 percent at 12 mg over 80 weeks. it is investigational, made by eli lilly, and not fda approved; lilly plans to file with the fda in the first quarter of 2027. because it is not an approved drug, fda says it cannot be legally compounded. The main differences lie in their mechanisms of action and clinical applications.
Which is better, Amycretin or Retatrutide?
Neither is universally "better" - the choice depends on your specific goals. Amycretin is typically used for weight loss purposes, while Retatrutide is used for weight loss. Always consult with a healthcare provider to determine which may be appropriate for your situation.
Can Amycretin and Retatrutide be used together?
Some peptide protocols combine multiple compounds for synergistic effects. However, using Amycretin and Retatrutide 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.