CagriSema vs Zepbound: in the only head-to-head trial, REDEFINE 4, Zepbound’s active ingredient tirzepatide produced more weight loss: 23.6% versus 20.2% of body weight over 84 weeks, and CagriSema failed its goal of proving it was at least as good.[1] Zepbound is FDA-approved and sold today.[6] CagriSema was submitted to FDA in December 2025, and as of mid-October 2026 no decision had been announced; Novo Nordisk expected one in the fourth quarter of 2026.[8][7]
For each drug in depth, see our cagrilintide and CagriSema profile and tirzepatide profile. For the wider field, see the GLP-1 drugs hub and our 2026 comparison of every GLP-1 drug.
At a glance
| CagriSema | Zepbound (tirzepatide) | |
|---|---|---|
| Maker | Novo Nordisk[8] | Eli Lilly[6] |
| What it is | Cagrilintide 2.4 mg + semaglutide 2.4 mg[8] | Tirzepatide 2.5 to 15 mg[6] |
| Targets | Amylin and calcitonin receptors + GLP-1 receptor[9][2] | GIP and GLP-1 receptors[6] |
| Dosing | Once weekly injection[2] | Once weekly injection[6] |
| Head-to-head weight loss (84 weeks) | −20.2%[1] | −23.6%[1] |
| Placebo-controlled trial, no diabetes | −20.4% at 68 weeks[2] | −20.9% at 72 weeks (15 mg)[4] |
| FDA status | Under review; decision expected Q4 2026[7] | Approved for weight management and sleep apnea[6] |
How they work
CagriSema pairs two hormone mimics. Semaglutide copies GLP-1, a gut hormone that curbs appetite. Cagrilintide is a long-acting version of amylin, a hormone the pancreas releases with insulin that slows stomach emptying and signals fullness.[9] In REDEFINE 1, the combination produced more weight loss than either part alone.[10]
Zepbound is a single molecule, tirzepatide, that activates both GIP and GLP-1 receptors.[6] It does not act on amylin receptors.
The idea behind CagriSema is that amylin and GLP-1 reduce appetite through partly different brain pathways, so adding them together could deepen weight loss.[9] Tirzepatide takes a different route to the same goal, pairing GLP-1 with a second gut hormone, GIP. Both produce far more weight loss than older GLP-1 drugs such as liraglutide; see liraglutide vs semaglutide for that comparison.
The head-to-head trial: REDEFINE 4
REDEFINE 4 randomized 809 adults with obesity and at least one related health problem to CagriSema 2.4 mg/2.4 mg or tirzepatide 15 mg for 84 weeks. It was open-label, so participants and investigators knew which drug was given.[1]
| Analysis | CagriSema | Tirzepatide 15 mg |
|---|---|---|
| All participants, regardless of stopping | −20.2% | −23.6%[1] |
| Participants who kept taking the drug | −23.0% | −25.5%[1] |
| Primary goal (non-inferiority) | Not met[1] | — |
“Non-inferiority” means the trial was designed to show CagriSema was not meaningfully worse than tirzepatide, a lower bar than proving it better. CagriSema missed even that bar. The second row counts only people who kept taking their drug, which shows what each can do when tolerated; tirzepatide still came out ahead by about 2.5 percentage points.[1]
Novo described side effects as mostly mild to moderate and gastrointestinal, but it did not publish rates in its announcement.[1] As of October 2026 we found no peer-reviewed publication of REDEFINE 4.
In type 2 diabetes, a separate 68-week head-to-head trial (REIMAGINE 4) found CagriSema was non-inferior to tirzepatide 15 mg on weight loss but not on blood sugar lowering; people on CagriSema lost 15.2% of their weight and lowered HbA1c by 1.9 percentage points.[7]
Results in placebo-controlled trials
| Trial | Drug | Who | Weeks | Weight change | Placebo |
|---|---|---|---|---|---|
| REDEFINE 1 | CagriSema | 3,417 without diabetes | 68 | −20.4% | −3.0%[2] |
| SURMOUNT-1 | Tirzepatide 15 mg | 2,539 without diabetes | 72 | −20.9% | −3.1%[4] |
| REDEFINE 2 | CagriSema | 1,206 with type 2 diabetes | 68 | −13.7% | −3.4%[3] |
| SURMOUNT-2 | Tirzepatide 15 mg | 938 with type 2 diabetes | 72 | −14.7% | −3.2%[5] |
Across separate trials, the two look similar, which is why the head-to-head result matters. In REDEFINE 1, only 57.3% of people on CagriSema were on the top dose at the end of the trial.[10]
Side effects and safety
- CagriSema: in REDEFINE 1, 79.6% had gastrointestinal side effects such as nausea, vomiting, diarrhea, constipation or abdominal pain, versus 39.9% on placebo; most were mild to moderate and temporary.[2] In REDEFINE 2, the figures were 72.5% versus 34.4%.[3]
- Zepbound: stomach side effects are also the most common, mostly during dose increases; 4.3% to 7.1% stopped because of side effects in SURMOUNT-1, versus 2.6% on placebo.[4]
- Shared warnings: Zepbound carries a boxed warning about thyroid C-cell tumors in rodents and should not be used with a personal or family history of medullary thyroid cancer or MEN 2.[6] CagriSema contains semaglutide, which carries the same warning; its final label is not yet known.
Other approved uses and outcomes data
- Zepbound is also approved for moderate to severe obstructive sleep apnea in adults with obesity, based on the SURMOUNT-OSA trials.[6][11]
- CagriSema has a heart outcomes trial (REDEFINE 3) in more than 7,000 people with heart disease under way.[15]
- Novo is also testing a higher-dose CagriSema (2.4 mg/7.2 mg), with results expected in the first half of 2028.[7]
Cost and access in 2026
| CagriSema | Zepbound | |
|---|---|---|
| Available in the US? | No; under FDA review[7] | Yes[6] |
| Self-pay (LillyDirect) | — | $299 (2.5 mg), $399 (5 mg), $449 (7.5 to 15 mg) a month[12] |
| Medicare GLP-1 Bridge | — | $50 a month for eligible enrollees (KwikPen)[13] |
See Zepbound cost without insurance for the 45-day refill rule and pen prices.
Who each may suit: questions for your clinician
- “I want the most weight loss available now.” Ask whether tirzepatide is appropriate; it outperformed CagriSema head to head and is approved.[1]
- “I didn’t tolerate or respond to tirzepatide.” Ask whether waiting for CagriSema, if approved, or trying a semaglutide product makes sense.
- “I have sleep apnea.” Zepbound is the one approved for it.[6]
- “I have type 2 diabetes.” Ask about blood sugar goals; in REIMAGINE 4, CagriSema did not match tirzepatide on HbA1c.[7]
The verdict
Today, Zepbound has the edge: it won the only head-to-head trial, it is approved, and it has a known price. CagriSema is still one of the most effective weight-loss treatments ever tested, with about 20% average weight loss, and it may give people another option if FDA approves it. What isn’t known yet: FDA’s decision, CagriSema’s final label and price, and the full peer-reviewed REDEFINE 4 data. Compare other next-generation drugs in survodutide vs tirzepatide, orforglipron vs tirzepatide and retatrutide vs tirzepatide.
