Cagrilintide vs. Retatrutide: What’s the Difference?

Is cagrilintide FDA-approved?

No. Here is where each one stands as of September 30, 2026:

• Cagrilintide on its own is investigational, meaning it is still being tested in clinical trials. Its own phase 3 program, RENEW, began in November 2025. Phase 3 is the last and largest stage of testing before a company asks for approval.
• CagriSema (cagrilintide plus semaglutide) is under FDA review. Novo Nordisk said in a press release that it filed a New Drug Application with the FDA on December 18, 2025. In a September 30, 2026 press release, Novo said it had filed with both the FDA and Health Canada in December 2025 and expects an FDA decision in the fourth quarter of 2026. Filing is not approval. In December 2025, Novo said CagriSema was not approved in the U.S. or the EU.
• Retatrutide is investigational. Lilly said in a September 29, 2026 press release that it plans to apply for U.S. approval in the first quarter of 2027.

The FDA says cagrilintide and retatrutide cannot be used in compounding under federal law. Neither is part of any FDA-approved drug, and neither has been found safe and effective for any condition. Products sold online as “research” cagrilintide are not CagriSema and not the trial drug. For what “investigational” and “research use” mean, see FDA-approved vs. investigational vs. research peptides.

What is cagrilintide?

What amylin does

Amylin is a hormone made in the pancreas that helps you feel full. Natural amylin is hard to turn into a medicine because it tends to clump into fibers. An older amylin drug, pramlintide, is used for diabetes alongside insulin. It wears off quickly, so it needs three injections a day.

How cagrilintide is built

An analog is a lab-made version of a natural hormone, changed so it works better as a medicine. Cagrilintide is an amylin analog with a fatty acid chain attached, which makes it last longer in the body. In an early study, half of each dose was still in the body after about 6.5 to 8 days (159 to 195 hours). That is why trials give it once a week.

Cagrilintide is an agonist, a molecule that switches a receptor on. It switches on amylin receptors and a related receptor called the calcitonin receptor. It does not act on the GLP-1 receptor.

What CagriSema is

CagriSema is a fixed-dose combination of cagrilintide 2.4 mg and semaglutide 2.4 mg, given as one weekly injection. Semaglutide is the GLP-1 drug in Ozempic and Wegovy. Most of Novo's phase 3 trials test this combination. Cagrilintide alone was mainly tested as a comparison group in those trials.

How cagrilintide and retatrutide work differently

Retatrutide is a single peptide that switches on three receptors: GLP-1, GIP and glucagon. Half of each dose was still in the body after about 6 days in an early study. For what each of those hormones does, see GLP-1 vs. GIP vs. glucagon and what is retatrutide.

The two drugs do not share a single target. Cagrilintide works through amylin receptors. Retatrutide works through the GLP-1, GIP and glucagon receptors. CagriSema and retatrutide do overlap on one receptor, GLP-1, because CagriSema contains semaglutide.

What the trials found

Cagrilintide alone

A phase 2 trial (The Lancet, 2021) gave 706 adults without diabetes one of five weekly cagrilintide doses for 26 weeks. Weight loss was 6.0% to 10.8%, versus 3.0% on placebo. That figure estimates the effect as if everyone took the drug as planned. In REDEFINE 1, the cagrilintide 2.4 mg group lost 11.5% at 68 weeks, counting everyone who started, Novo said in a press release.

CagriSema: REDEFINE 1 and 2

REDEFINE 1 was a phase 3 trial of 3,417 adults with obesity, or overweight plus a related health problem, and no diabetes. After 68 weeks, people on CagriSema lost 20.4% of their weight on average, versus 3.0% on placebo, counting everyone who started (NEJM, 2025). Novo said in a press release that the figure was 22.7% versus 2.3% when estimated as if everyone stayed on treatment. People could lower their dose during the trial, and Novo said 57.3% of the CagriSema group was on the top dose at the end.

REDEFINE 2 enrolled 1,206 adults with type 2 diabetes. After 68 weeks, weight fell 13.7% on CagriSema versus 3.4% on placebo (NEJM, 2025).

Retatrutide: TRIUMPH-1 and 2

TRIUMPH-1 was a phase 3 trial of 2,339 adults with obesity and no diabetes. After 80 weeks, people on 12 mg lost 25.0% of their weight, versus 3.9% on placebo, counting everyone who started (NEJM, 2026). Lilly's press release gave 28.3% versus 2.2% when estimated as if everyone stayed on treatment. For more, see TRIUMPH-1 results.

TRIUMPH-2 enrolled 1,152 adults with obesity and type 2 diabetes. After 80 weeks, weight fell 18.8% on 12 mg versus 5.1% on placebo (The Lancet, 2026).

Why these numbers can't be lined up

These are separate trials. They enrolled different people, ran for different lengths (68 versus 80 weeks) and handled dose changes differently: REDEFINE 1 let people lower their dose. So the gaps in this table do not show which drug works better. Only a head-to-head trial can do that, and none has compared cagrilintide or CagriSema with retatrutide. CagriSema has been tested head to head against tirzepatide instead. In REDEFINE 4, an 84-week obesity trial, Novo said CagriSema did not meet its main goal of showing weight loss at least close to tirzepatide's.

Side effects in the trials

Stomach and gut effects were the most common for both drugs.

• Cagrilintide alone (phase 2): stomach and gut effects in 41% to 63% across doses, versus 32% on placebo. Nausea was 20% to 47%, versus 18%. Injection-site reactions were also common.
• CagriSema (REDEFINE 1): stomach and gut effects in 79.6%, versus 39.9% on placebo (NEJM). Novo said in a press release that nausea affected 55% (placebo 12.6%) and vomiting 26.1% (placebo 4.1%). It said 5.9% stopped because of side effects, versus 3.5% on placebo.
• Retatrutide (TRIUMPH-1, 12 mg): Lilly said in a press release that nausea affected 42.4% (placebo 14.8%). Dysesthesia, an unusual skin feeling such as tingling, affected 12.5% (placebo 0.9%). It said 11.3% stopped because of side effects, versus 4.9% on placebo. In the phase 2 trial, heart rate rose with dose and peaked at 24 weeks. See retatrutide side effects.

These rates also come from separate trials with different designs. They are not a safety ranking.

Doses used in the trials

In trials, both drugs started low and went up in steps. Retatrutide started at 2 mg and rose every four weeks toward 4, 9 or 12 mg. In an early CagriSema study, both parts went up every four weeks over 16 weeks to the target dose. These are research doses only. Neither drug has an approved dose or schedule.