Quick answer: in the CagriSema vs retatrutide comparison, retatrutide has produced larger average weight loss in its trials: 25.0% at 80 weeks on the 12 mg dose, versus 20.4% at 68 weeks for CagriSema.[6][1] But the two have never been tested head to head, and the trials differ in length and design. CagriSema is under FDA review; retatrutide has not yet been submitted. Neither was FDA-approved as of mid-October 2026.[4][9]
For each drug in depth, see our CagriSema guide and the retatrutide profile.
At a glance
| CagriSema | Retatrutide | |
|---|---|---|
| Maker | Novo Nordisk | Eli Lilly |
| What it is | Cagrilintide 2.4 mg + semaglutide 2.4 mg | One molecule, tested at 4, 9 and 12 mg |
| Receptors | Amylin and calcitonin + GLP-1 | GIP + GLP-1 + glucagon |
| Dosing | Once weekly injection | Once weekly injection |
| Main obesity trial | REDEFINE 1: −20.4% at 68 weeks | TRIUMPH-1: −25.0% (12 mg) at 80 weeks |
| Versus tirzepatide | Lost (REDEFINE 4) | TRIUMPH-5 under way |
| FDA status (Oct 2026) | Submitted Dec 2025; decision expected late 2026 | Submission planned Q1 2027 |
Sources: REDEFINE 1,[1] TRIUMPH-1,[6] Novo Nordisk[4] and Lilly.[9]
How they work
CagriSema combines two hormone mimics. Semaglutide copies GLP-1, a gut hormone that curbs appetite. Cagrilintide is a long-acting version of amylin, a hormone released with insulin that slows stomach emptying, suppresses glucagon after meals and signals fullness to the brain.[10] Because amylin and GLP-1 act through partly different pathways, the idea is that together they reduce appetite more than either alone. In REDEFINE 1 they did: 20.4% weight loss with the combination versus 14.9% with semaglutide and 11.5% with cagrilintide alone.[3]
Retatrutide is a single peptide that switches on three receptors: GIP and GLP-1 (the same pair as tirzepatide) plus the glucagon receptor, which is thought to increase energy use.[6] Our guide to how retatrutide works explains the triple-agonist idea.
Both last about a week in the body. Cagrilintide’s half-life was 159 to 195 hours in an early trial,[16] and retatrutide’s about 6 days.[17]
Weight loss results side by side
| Trial | Who | Weeks | Result | Placebo |
|---|---|---|---|---|
| REDEFINE 1 (CagriSema) | 3,417 adults, no diabetes | 68 | −20.4% | −3.0% |
| TRIUMPH-1 (retatrutide 9 mg / 12 mg) | 2,339 adults, no diabetes | 80 | −23.7% / −25.0% | −3.9% |
| REDEFINE 2 (CagriSema) | 1,206 adults with type 2 diabetes | 68 | −13.7% | −3.4% |
| TRIUMPH-2 (retatrutide 9 mg / 12 mg) | 1,152 adults with type 2 diabetes | 80 | −16.8% / −18.8% | −5.1% |
Sources: REDEFINE 1,[1] TRIUMPH-1,[6] REDEFINE 2[2] and TRIUMPH-2.[8] All four figures count everyone randomized, whether or not they kept taking the drug.
Looking only at people who stayed on treatment, the companies reported 22.7% for CagriSema[3] and 28.3% for retatrutide 12 mg.[7]
Why this isn’t a fair fight
- Different lengths. Retatrutide’s main trials ran 80 weeks, 12 weeks longer than CagriSema’s 68.
- Different dosing rules. REDEFINE 1 let people stay on lower doses, and only 57.3% of the CagriSema group were on the top dose at week 68.[3]
- Different populations. Average starting weight, sex mix and countries differed.
Only a head-to-head trial can settle it, and none exists. Each drug has instead been tested against tirzepatide. In REDEFINE 4, tirzepatide 15 mg beat CagriSema (23.6% versus 20.2% at 84 weeks), and CagriSema failed to show it was at least as effective.[4] Retatrutide’s comparison, TRIUMPH-5, has an estimated primary completion of November 2026.[15] See CagriSema vs Zepbound and retatrutide vs tirzepatide.
Side effects compared
Both drug types mainly cause stomach and bowel side effects, especially while the dose is being raised.
- CagriSema: in REDEFINE 1, 79.6% had gastrointestinal side effects such as nausea, vomiting, diarrhea, constipation or stomach pain, versus 39.9% on placebo. Most were temporary and mild to moderate.[1] In REDEFINE 2 the figures were 72.5% versus 34.4%.[2]
- Retatrutide: in TRIUMPH-1, nausea affected 28.6% to 42.4% depending on dose, vomiting 10.6% to 25.3%, and diarrhea 25.2% to 34.1%, versus 14.8%, 4.8% and 13.5% on placebo.[7]
- Stopping because of side effects: 4.1%, 6.9% and 11.3% on retatrutide 4, 9 and 12 mg, versus 4.9% on placebo, in TRIUMPH-1.[7] In TRIUMPH-2 it was 4% to 12%, versus 5%.[8]
Retatrutide also has two effects that the published CagriSema summaries do not report:
- Dysesthesia, an abnormal skin sensation such as tingling, in 5.1% to 12.5% of people in TRIUMPH-1 versus 0.9% on placebo.[7]
- Heart rate rose with dose in its phase 2 trial, peaked at 24 weeks and then declined.[11]
The rates above come from different trials and reporting methods, so they cannot be compared like for like. For more detail, see retatrutide side effects.
Doses and how they are reached
- CagriSema: the main trials used cagrilintide 2.4 mg plus semaglutide 2.4 mg once a week, reached gradually over 16 weeks.[1] Lower combinations (1.0/1.0 mg and 1.7/1.7 mg) also beat placebo in the REDEFINE 9 trial, and a higher-dose version with semaglutide 7.2 mg started phase 3 in 2026.[5]
- Retatrutide: phase 3 tested 4, 9 and 12 mg once weekly, starting at 2 mg and increasing every four weeks.[7] See the retatrutide dosage guide.
These are trial doses, not prescribing guidance. If either drug is approved, its label will set the doses.
Heart outcomes: still unknown for both
Neither drug yet has results from a heart outcomes trial. CagriSema’s REDEFINE 3 has randomized 7,076 adults with established heart disease.[13] Retatrutide’s TRIUMPH-Outcomes is following about 10,000 adults, with an estimated primary completion in February 2029.[14]
FDA status and availability
- CagriSema was submitted to FDA for weight management in December 2025, and Novo Nordisk said a decision was anticipated by late 2026.[4] Its August 2026 half-year report still listed a US decision among its expected 2026 milestones.[5] We found no approval in FDA’s databases as of October 18, 2026.
- Retatrutide: Lilly says its data package is complete and it plans to submit a Biologics License Application in the first quarter of 2027.[9] See when will retatrutide be available?
FDA says cagrilintide and retatrutide cannot be used in compounding and have not been found safe and effective for any condition. Products sold online under either name are unapproved and of unknown quality.[12] Combining them is untested; see cagrilintide with retatrutide.
Which might suit whom: questions for a clinician
- Would an approved drug, such as tirzepatide or semaglutide, meet my goals now?
- If I didn’t tolerate a GLP-1 drug, would an amylin-based option be worth waiting for?
- Am I eligible for a trial of either drug?
- How would we manage nausea, and what else should we monitor, such as heart rate?
For a wider view of the field, see retatrutide vs semaglutide and retatrutide weight loss results.
