Retatrutide and cagrilintide: what is known about the combination

Retatrutide and cagrilintide are two investigational weight-loss drugs that have never been tested together in people. Retatrutide (Eli Lilly) acts on three gut-hormone receptors and has phase 3 trial results; cagrilintide (Novo Nordisk) is a long-acting amylin analogue with a published phase 2 trial of its own and phase 3 results reported mainly as part of CagriSema. Neither is FDA-approved, and neither can be obtained legally outside clinical trials (plus, for retatrutide only, a narrow physician-requested expanded access program). The only study of the pair is a 2026 experiment in obese male rats [Animal].

Item	Retatrutide	Cagrilintide
US FDA status	Investigational; not approved for any use	Investigational; filed only as part of CagriSema (December 2025), not approved
Compounding (503A/503B)	Cannot be compounded under federal law (FDA)	Cannot be compounded under federal law (FDA)
WADA 2026	Not named; falls under S0 non-approved substances while unapproved	Not named; falls under S0 non-approved substances while unapproved
Strongest evidence	Human RCT, phase 3 (n=2,339)	Human RCT, phase 2 alone (n=706 on drug); phase 3 results reported mainly with semaglutide
Human trials of the combination	None registered	None registered
Next regulatory step	Lilly says it plans to submit retatrutide to the FDA in Q1 2027 (company release, July 2026)	FDA review of CagriSema expected in 2026 (Novo Nordisk); no filing announced for cagrilintide alone
Last checked	2026-10-04	2026-10-04

Retatrutide and cagrilintide at a glance

Feature	Retatrutide	Cagrilintide
Developer	Eli Lilly	Novo Nordisk
Class	GIP, GLP-1 and glucagon receptor agonist (“triple agonist”)	Long-acting amylin analogue (amylin and calcitonin receptor agonist)
Main research focus	Obesity, type 2 diabetes, knee osteoarthritis pain, sleep apnea	Obesity and type 2 diabetes, mostly combined with semaglutide
Best weight result	−25.0% vs −3.9% placebo at 80 weeks [Human RCT]	−10.8% vs −3.0% placebo at 26 weeks [Human RCT]
Route studied	Once-weekly injection under the skin	Once-weekly injection under the skin
Main safety concerns	Nausea, diarrhea, heart-rate rise, low blood pressure, dysesthesia	Nausea, constipation, diarrhea, injection-site reactions
Approval	None	None (CagriSema under FDA review)
Combination data	One rat study (2026) [Animal]; no human data

What is retatrutide?

Retatrutide is a single molecule that activates three hormone receptors: those for the gut hormones GIP and GLP-1, plus the receptor for glucagon. In the phase 2 obesity trial (338 adults, 48 weeks), the 12 mg arm lost 24.2% of body weight versus 2.1% on placebo [Human RCT, n=338]. Phase 3 trials have since reported large losses in people without diabetes and in people with obesity and type 2 diabetes (TRIUMPH-2) [Human RCT, n=1,152]. For how retatrutide sits beside the approved drugs, see our retatrutide vs tirzepatide vs semaglutide comparison.

What is cagrilintide?

Cagrilintide is a long-acting analogue of amylin, a pancreatic hormone that induces satiety (fullness). In the phase 2 dose-finding trial (706 people on cagrilintide, 26 weeks), weight fell 6.0% to 10.8% across doses versus 3.0% on placebo, and the top dose beat liraglutide 3.0 mg (10.8% vs 9.0%) [Human RCT]. Novo Nordisk then paired it with semaglutide as CagriSema; the REDEFINE 1 trial reported −20.4% versus −3.0% with placebo at 68 weeks [Human RCT, n=3,417]. A cagrilintide-only phase 3 trial (NCT07220642) is under way.

How they work differently

• Retatrutide: acts on GIP, GLP-1 and glucagon receptors; the phase 2 paper describes it as an agonist of all three.
• Cagrilintide: acts on amylin and calcitonin receptors. In mice, its weight loss depended on the amylin receptor subtypes AMY1R and AMY3R and activated neurons in the dorsal vagal complex, a brainstem region (Carvas 2025) [Animal].
• Together: the two drugs hit five receptor types with no overlap. The authors of the 2026 rat study call this “five-receptor polypharmacology” and present it as a design idea for future single molecules [Animal].

What is known about retatrutide and cagrilintide together?

Only one study has tested the pair. Researchers at the University of Copenhagen’s Novo Nordisk Foundation Center for Basic Metabolic Research gave daily co-administration to diet-induced obese male rats (Petersen 2026, Nature Metabolism) [Animal]. Their findings:

• Weight and food intake fell in a dose-dependent way, by more than with either drug alone at the same molar dose.
• The pair also beat matched-dose comparator combinations that included semaglutide or tirzepatide.
• Cholesterol, triglycerides and insulin improved.
• Pair-feeding tests showed the extra weight loss was not explained by eating less alone.

These are rat results. They show the idea is worth testing; they do not show the combination works or is safe in humans. A ClinicalTrials.gov search found no registered trial of retatrutide with cagrilintide or any other amylin drug. No controlled human study has tested the combination.

The closest human evidence is indirect. CagriSema, which pairs cagrilintide with the GLP-1 drug semaglutide, has two published phase 3 trials, and Lilly has completed a phase 1 study of its own amylin drug eloralintide given with tirzepatide (NCT06916065, 188 participants). Neither tells us how retatrutide’s glucagon action and cagrilintide’s amylin action behave together in people, including on heart rate, blood pressure or how much nausea people can tolerate.

Evidence head-to-head

Outcome	Retatrutide best evidence	Cagrilintide best evidence
Weight, no diabetes	Human RCT, phase 3 (n=2,339): TRIUMPH-1	Human RCT, phase 2 (n=706 on drug): Lau 2021
Weight, type 2 diabetes	Human RCT, phase 3 (n=1,152): TRIUMPH-2	Only as CagriSema, Human RCT (n=1,206): REDEFINE 2
Blood sugar (HbA1c)	Human RCT, phase 3 (n=537): TRANSCEND-T2D-1	Only as CagriSema: REDEFINE 2
Knee pain, sleep apnea	Human RCT subgroups: TRIUMPH-1	No published trial
Heart and kidney outcomes	Trial running: NCT06383390	No published trial
The two drugs combined	Animal only: Petersen 2026

On published numbers, retatrutide has the deeper evidence base: three phase 3 trials published in 2026 with more than 4,000 participants between them. Cagrilintide on its own has one published phase 2 trial and a 302-person cagrilintide-only arm in REDEFINE 1; most of its human data come from the CagriSema program, where its separate contribution is harder to isolate. How we grade these levels is explained on our how we compare peptides page.

How long do effects take in studies?

• Retatrutide: in the phase 2 trial, the 12 mg arm had lost 17.5% at 24 weeks and 24.2% at 48 weeks, so weight was still falling at the six-month mark [Human RCT, n=338]. In TRIUMPH-1 the endpoint was 80 weeks.
• Cagrilintide: the phase 2 trial measured its result at 26 weeks [Human RCT]; CagriSema trials ran 68 weeks.
• Combination: no human timeline exists.

Safety and regulatory status

Side effects seen in trials

Retatrutide. In TRIUMPH-2 (adults with obesity and type 2 diabetes), diarrhea affected 34% on the two higher doses versus 13% on placebo, and nausea up to 28% versus 8% [Human RCT, n=1,152]. Low blood pressure (up to 6% vs under 1%) and dysesthesia, an abnormal skin sensation (up to 7% vs 1%), were also more common. Stopping treatment because of side effects or death reached 12% in the 9 mg arm versus 5% with placebo; investigators judged all deaths unrelated to the drug. The phase 2 trial found dose-dependent heart-rate increases that peaked at 24 weeks and then declined.

Cagrilintide. In the phase 2 trial, gastrointestinal side effects hit 41% to 63% of people on cagrilintide versus 32% on placebo, mainly nausea (20% to 47% vs 18%); injection-site reactions were also common [Human RCT]. With semaglutide in REDEFINE 1, gastrointestinal events affected 79.6% versus 39.9% on placebo [Human RCT, n=3,417].

Together. No human safety data exist. Each drug causes mainly gastrointestinal side effects on its own, so added gastrointestinal effects are a plausible concern, but that is an inference, not a trial finding.

Products sold outside trials

The FDA states that retatrutide and cagrilintide “are not components of FDA-approved drugs and have not been found safe and effective for any condition”, that neither can be used in compounding under federal law, and that it has warned companies selling retatrutide “falsely labeled ‘for research purposes’ or ‘not for human consumption.’” A 2026 case report describes a man with type 1 diabetes admitted with vomiting, high ketones and acute kidney injury after self-administering an online product sold as retatrutide; an infection was also present, so the authors could not establish cause [Human case report, n=1]. They note that the composition and purity of such products may be uncertain.

Status by jurisdiction

• United States: neither drug is approved (FDA, above). Novo Nordisk filed CagriSema with the FDA on December 18, 2025 and says it “is not approved in the US or EU”. Lilly runs a single-patient expanded access program for retatrutide, requested by a treating physician, for adults with a BMI of 35 or more despite the highest available dose of approved weight-management therapy, at least two serious obesity complications and no access to a trial.
• United Kingdom: the MHRA reported its largest-ever seizure of unlicensed weight-loss medicines in May 2026: about 12,000 doses recovered from a site believed to make and distribute unlicensed weight-loss medicines, including retatrutide.
• Sport: the WADA 2026 Prohibited List bans at all times any substance “with no current approval by any governmental regulatory health authority for human therapeutic use (e.g. drugs under pre-clinical or clinical development…)”. Neither drug is named on the list; as investigational drugs they fall into this S0 class until approved somewhere.