SharpyCagriSema vs Tirzepatide: REIMAGINE 5 and REDEFINE 4 Explained
CagriSema vs tirzepatide has two head-to-head answers, and they depend on the dose. In REIMAGINE 5, low-dose CagriSema (1.0/1.0 mg) beat tirzepatide 5 mg on weight loss in type 2 diabetes, 12.4% vs 9.1% at 60 weeks, with similar A1C drops. In REDEFINE 4, full-dose CagriSema (2.4/2.4 mg) fell short of tirzepatide 15 mg in obesity. CagriSema is not FDA approved yet. On any of these drugs, Sharpy helps you protect muscle with one protein target and one 20-minute workout a day.
Which works better, CagriSema or tirzepatide? It depends on the dose. At low doses in people with type 2 diabetes, CagriSema won on weight loss. At top doses in people with obesity, tirzepatide won. Some headlines this week quote only the first result. Novo Nordisk repeated it in its November 4 earnings report: 12.4% weight loss with CagriSema versus 9.1% with tirzepatide 5 mg. That number is real, but it does not mean CagriSema beats Zepbound or Mounjaro at the doses many people reach.
CagriSema is a weekly shot that pairs cagrilintide (an amylin-like drug) with semaglutide (the drug in Wegovy). Tirzepatide is one molecule that acts on GIP and GLP-1 receptors, sold by Eli Lilly as Mounjaro for type 2 diabetes and Zepbound for weight loss. Our main CagriSema guide covers the basics.
CagriSema vs tirzepatide head to head: both trials
| REIMAGINE 5 | REDEFINE 4 | |
|---|---|---|
| Who was in it | Type 2 diabetes, BMI 30 or higher | Adults with obesity |
| People enrolled | 1,023 | 809 |
| Main check | Week 60 | Week 84 |
| Did people know their drug? | Yes (open label) | Yes (open label) |
| CagriSema dose | 1.0/1.0 mg | 2.4/2.4 mg |
| Tirzepatide dose | 5 mg | 15 mg |
| Weight loss if people stayed on the drug | 12.4% vs 9.1% | 23.0% vs 25.5% |
| Weight loss counting everyone | Not released | 20.2% vs 23.6% |
| A1C drop | 1.71 vs 1.67 points | Not a main goal |
| Who came out ahead | CagriSema on weight, A1C close | Tirzepatide |
The first number in each cell is CagriSema. Novo Nordisk ran both trials.
REIMAGINE 5 results: what the numbers mean
REIMAGINE 5 enrolled adults whose A1C was 7% to 10.5% on metformin, an SGLT2 inhibitor or both. It had two main goals, and CagriSema met both:
- Weight: superior to tirzepatide 5 mg. The gap was 3.3 percentage points.
- A1C: non-inferior to tirzepatide 5 mg. That means it was not meaningfully worse. It does not mean it was better.
Three limits matter when you read this:
- The doses are low. Tirzepatide 5 mg is the lowest maintenance dose on the Zepbound label, which goes up to 15 mg. The Mounjaro label also goes up to 15 mg. This trial tells you nothing about how CagriSema stacks up against those higher doses in type 2 diabetes.
- The results are from the company. Novo reported them on September 21, 2026, as topline data. As of this writing we have not found a peer-reviewed paper. Novo's weight figures use the "efficacy estimand," which estimates results if people stay on treatment. Numbers that count everyone are usually lower.
- Side effect rates are not public. Novo says only that CagriSema was "well tolerated overall." We will update this guide when the rates are published.
CagriSema vs Zepbound: why the top-dose trial matters more for weight loss
If your goal is the most weight loss, REDEFINE 4 is the closer match. It tested the top CagriSema dose against the top tirzepatide dose. Tirzepatide led by 2.5 points when counted as if people stayed on the drug, and by 3.4 points when everyone was counted. CagriSema also missed its main goal of proving non-inferiority.
Both drugs still caused large losses. Average losses above 20% are large on either drug, so a second strong option may still matter for some people.
Results by dose across separate trials
These trials had different people, lengths and ways of counting, so this is a rough guide and not a ranking.
| Trial | Group | Drug and dose | Weight loss | Placebo |
|---|---|---|---|---|
| REDEFINE 1, 68 weeks | Obesity | CagriSema 2.4/2.4 mg | 20.4% | 3.0% |
| REDEFINE 9, 68 weeks | Obesity | CagriSema 1.0/1.0 mg | 21.0%* | 2.0%* |
| SURMOUNT-1, 72 weeks | Obesity | Tirzepatide 15 mg | 20.9% | 3.1% |
| SURMOUNT-1, 72 weeks | Obesity | Tirzepatide 5 mg | 15.0% | 3.1% |
| REDEFINE 2, 68 weeks | Type 2 diabetes | CagriSema 2.4/2.4 mg | 13.7% | 3.4% |
| SURMOUNT-2, 72 weeks | Type 2 diabetes | Tirzepatide 15 mg | 14.7% | 3.2% |
| SURMOUNT-2, 72 weeks | Type 2 diabetes | Tirzepatide 10 mg | 12.8% | 3.2% |
*If people stayed on treatment. The other rows count people regardless of whether they stayed on the drug, so REDEFINE 9 looks better here than it would on the same basis.
Two patterns stand out. People with type 2 diabetes tended to lose less on both drugs; our GLP-1 and diabetes guide covers this group. And in SURMOUNT-1, the 15 mg tirzepatide dose led to more loss than 5 mg.
CagriSema vs tirzepatide side effects
Both drugs mostly cause stomach side effects, and both raise doses in steps to help limit them. CagriSema has no FDA label yet, so these numbers are from trials and may change.
| Side effect | CagriSema 2.4/2.4 mg (REDEFINE 1) | Zepbound 15 mg (label) |
|---|---|---|
| Nausea | 55% | 28% |
| Vomiting | 26.1% | 13% |
| Constipation | 30.7% | 11% |
Do not treat this table as a head-to-head. The trials differ, and side effects were counted in different groups. Approved tirzepatide and semaglutide medicines carry an FDA boxed warning about thyroid C-cell tumors. If stomach effects are a problem now, our nausea guide can help, and your prescriber can review your dose.
Is CagriSema FDA approved? Price and availability
- FDA status: not approved as of November 6, 2026. Novo filed for weight management in December 2025 and has said it expects a decision in the fourth quarter of 2026.
- US launch: Novo's CEO wrote in the November 4 report that the company is "preparing for the US launch of CagriSema in early 2027, subject to regulatory approval."
- Type 2 diabetes: the FDA filing we can confirm is for weight management. We could not confirm a diabetes filing or approval.
- Price: not announced. For what tirzepatide costs today, see our LillyDirect Zepbound guide.
- Online sellers: anything sold today as CagriSema or a "cagri-sema blend" is not an approved medicine. Avoid it.
What this means if you take Mounjaro or Zepbound
Nothing about your treatment changes today. Do not stop or change your dose because of a headline. If you have type 2 diabetes and want to know about new options, ask your prescriber once CagriSema has a label. The questions to ask then are which doses are approved, whether insurance covers it and whether your current drug is still working for you. Curious about what comes after these two? Read our retatrutide guide. And for how the two tirzepatide brands differ, see Zepbound vs Mounjaro.
Keep the weight loss from costing you muscle
Novo's release does not report muscle or body composition results from REIMAGINE 5. Whichever drug you use, part of the weight you lose can be lean mass. You can act on that now: set a daily protein target and do regular resistance training. Sharpy sets one protein target and one 20-minute workout a day, then shows a Shape Score so you can see whether your shape is changing, not only the number on the scale.
The bottom line
CagriSema beat tirzepatide 5 mg on weight loss in type 2 diabetes. Tirzepatide 15 mg beat full-dose CagriSema in obesity. Tirzepatide is the option you can get today, and CagriSema still needs an FDA decision. Talk to your prescriber before any change, and keep building the habits that protect muscle on either drug. Sharpy keeps those habits simple.
Sources
- Novo Nordisk: CagriSema delivers superior weight loss versus tirzepatide 5 mg in REIMAGINE 5, September 21, 2026, via Yahoo Finance
- BioPharm International: CagriSema beats tirzepatide for weight loss in phase 3 trial, September 22, 2026
- REIMAGINE 5 study record, ClinicalTrials.gov NCT06534411
- Novo Nordisk company announcement 65/2026, Form 6-K, November 4, 2026
- HCPLive: REDEFINE 4 results, February 2026
- American College of Cardiology: REDEFINE 1 and REDEFINE 2 journal scan, July 2025
- Zepbound prescribing information via DailyMed, August 2026
- Jastreboff AM et al. Tirzepatide once weekly for the treatment of obesity (SURMOUNT-1), NEJM 2022
- Garvey WT et al. Tirzepatide for obesity in people with type 2 diabetes (SURMOUNT-2), Lancet 2023
Questions people ask
Is CagriSema better than tirzepatide?
It depends on the doses compared. CagriSema 1.0/1.0 mg beat tirzepatide 5 mg on weight loss in REIMAGINE 5 (12.4% vs 9.1%). Tirzepatide 15 mg beat CagriSema 2.4/2.4 mg in REDEFINE 4 (25.5% vs 23.0%). No trial shows CagriSema beating tirzepatide at its top dose.
What is the REIMAGINE 5 trial?
REIMAGINE 5 is a Novo Nordisk phase 3 trial of 1,023 adults with type 2 diabetes and a BMI of 30 or higher. Everyone knew which drug they took. It compared weekly CagriSema 1.0/1.0 mg with tirzepatide 5 mg, and checked A1C and body weight at week 60.
What were the REIMAGINE 5 results?
Novo reported 12.4% weight loss with CagriSema and 9.1% with tirzepatide 5 mg, which met the test for superior weight loss. A1C fell by 1.71 points with CagriSema and 1.67 with tirzepatide, which met the test for non-inferior, meaning not meaningfully worse. These are company results, not yet a full journal paper.
Is CagriSema FDA approved?
Not as of November 6, 2026. Novo filed for weight management in December 2025 and has said it expects an FDA decision in the fourth quarter of 2026. Its November report says it is preparing a US launch in early 2027, subject to approval.
Is CagriSema or Zepbound better for weight loss?
Zepbound is the only one of the two you can get today. In the one trial of top doses, REDEFINE 4, tirzepatide 15 mg led by about 2.5 to 3.4 points, depending on how the results were counted. Zepbound is the weight loss brand of tirzepatide.
How do CagriSema vs tirzepatide vs retatrutide compare?
Tirzepatide is approved and sold as Mounjaro and Zepbound. CagriSema is under FDA review. Retatrutide is still investigational. Only CagriSema and tirzepatide have been compared directly in the trials covered here, so any ranking with retatrutide comes from separate studies.
Should I switch from Mounjaro or Zepbound to CagriSema?
You cannot switch now, because CagriSema is not approved or sold. Products sold online as CagriSema or cagri-sema blends are not approved medicines. If it is approved, any change is a decision for you and your prescriber.