Does CagriSema or Tirzepatide Cause More Weight Loss?

After 84 weeks in the REDEFINE 4 head-to-head trial, people on tirzepatide 15 mg lost an average of 23.6% of their body weight and people on CagriSema lost 20.2%, according to Healio's report on the REDEFINE 4 results.

How much weight did people lose on each in the head-to-head trial?

REDEFINE 4 randomly assigned 809 adults with obesity and at least one weight-related health condition to once-weekly treatment with either CagriSema or tirzepatide 15 mg. CagriSema is a fixed-dose combination of two drugs, cagrilintide 2.4 mg and semaglutide 2.4 mg, given once a week (Novo Nordisk announcement). The trial was open-label, which means participants and investigators knew which drug each person was getting.

The trial has two reported numbers for CagriSema. Healio reported 20.2% weight loss for CagriSema alongside 23.6% for tirzepatide, and those are the like-for-like figures. Novo Nordisk's announcement reported 23% for CagriSema from a different analysis and did not give a tirzepatide figure from that same analysis in the portions we reviewed. Comparing 23% with 23.6% would mix two different calculations. Both sources agree on the outcome. The trial was designed to show that CagriSema loses no meaningful ground to tirzepatide, which is the "non-inferiority" goal, and CagriSema did not meet it.

Healio reported that CagriSema was well tolerated and that most of its stomach and digestive side effects were mild or moderate. Novo Nordisk says other trials are now testing higher-dose CagriSema combinations.

Does either one control appetite better?

The two drugs share one part of how they work and differ in another. Healio describes CagriSema as cagrilintide, which acts on receptors for the hormone amylin, paired with semaglutide, a GLP-1 drug. Tirzepatide is a single molecule that acts on two hormone receptors, GIP and GLP-1. That is why it is called a dual agonist. Both treatments therefore act on GLP-1 receptors, and each adds a different second hormone target.

None of the REDEFINE 4 results we reviewed include hunger or fullness ratings, and we found no study comparing appetite on these two drugs. A difference in hormone targets does not show how hungry you will feel from week to week. If appetite is your main concern, the trial reports which drug had the higher average weight loss. It does not show which one made people feel less hungry.

Which one can you actually start, and what does it cost?

In the U.S., tirzepatide is available by prescription now. As Zepbound, it is prescribed for adults with obesity, or adults with overweight plus at least one weight-related health condition, alongside a reduced-calorie diet and more physical activity (Lilly's Zepbound clinical data).

A separate trial found substantial average weight loss below the 15 mg dose used in the head-to-head trial, but it does not show which dose you need. In Lilly's SURMOUNT-1 trial, people who stepped up once, from 2.5 mg to the 5 mg maintenance dose, lost an average of 15% of their body weight at 72 weeks. People on placebo lost 3.1%. SURMOUNT-1 is a separate 72-week trial, not part of REDEFINE 4, so its different participants and time point mean this figure is not a direct dose-to-dose comparison with the head-to-head results or a forecast of what you will lose. Your doctor decides your starting dose and whether to increase it.

Lilly's U.S. Zepbound page, which shows no publication date and was viewed in October 2026, says "Millions of Medicare Part D patients may be eligible to get Zepbound for no more than $50/month." Lilly says this applies to eligible Medicare Part D patients with a Zepbound prescription for weight management, that eligibility is based on the Medicare GLP-1 Bridge Clinical Criteria, and that coverage is not guaranteed. The same page says the Zepbound KwikPen is available at the same self-pay prices, with terms applying and taxes and fees possible.

The sources reviewed here describe CagriSema only in clinical trials, including Novo Nordisk's February 2026 announcement that further REDEFINE trials are under way. None of them describe an approval or a way to get a CagriSema prescription. Hot or Nothing's weight plans include tirzepatide and semaglutide. Start with the Hot or Nothing quiz. It is the first step toward a doctor-led assessment of which medication and dose fit your goals.