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    Research 12 min readOct 25, 2026 Fact-checked

    Eloralintide vs Cagrilintide: Two Amylin Drugs Compared

    Two weekly amylin drugs, one selective and one dual: how eloralintide and cagrilintide differ on receptors, weight loss, side effects and phase 3 timing.

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    BioChonch

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    Evidence notes from published research and trial registries. Educational information, not medical advice.

    Key Takeaway

    Two weekly amylin drugs, one selective and one dual: how eloralintide and cagrilintide differ on receptors, weight loss, side effects and phase 3 timing.

    Eloralintide and cagrilintide are both long-acting amylin drugs injected once a week, and on published numbers eloralintide looks stronger as a single drug. They differ in reach: eloralintide (Eli Lilly) is a selective amylin receptor agonist, while cagrilintide (Novo Nordisk) also switches on the calcitonin receptor. Eloralintide's best phase 2 arm lost 20.1% of body weight at 48 weeks, against 0.4% on placebo. Cagrilintide on its own lost 11.8% at 68 weeks, against 2.3% in the phase 3 REDEFINE 1 trial. No study has tested one against the other, and the designs differ enough that the true size of the gap is unknown. Neither drug is approved as a single agent. Every dose below comes from a named trial.

    The two drugs side by side

    Detail Eloralintide Cagrilintide
    Developer and code Eli Lilly, LY3841136 Novo Nordisk, NNC0174-0833 (registry)
    Receptor profile About 12 times more potent at the AMY1 amylin receptor than at the calcitonin receptor (Briere 2025) Similar potency at AMY1, AMY3 and the calcitonin receptor (Briere 2025)
    Half-life 12.9 to 15.3 days after one dose (Briere 2025) 159 to 195 hours, or 6.6 to 8.1 days (Enebo 2021)
    Doses tested Single doses of 0.04 to 12 mg (Briere 2025); 1 to 9 mg weekly in phase 2 (NCT06230523); four unnamed doses in phase 3 (NCT07321886) 0.3 to 4.5 mg weekly in phase 2 (Lau 2021); 2.4 mg in phase 3 (NCT05567796)
    Furthest stage alone Phase 3, five ENLIGHTEN trials (ENLIGHTEN-1) Phase 3, RENEW 1 and 2 (RENEW 1)
    Main combination EloraTZP, with tirzepatide CagriSema, with semaglutide

    Same hormone, different reach

    Amylin receptors are hybrids, the calcitonin receptor paired with one of three RAMP proteins to make AMY1, AMY2 and AMY3 (Briere 2025).

    In Lilly's cell assays, eloralintide was about 12-fold more potent at human AMY1 than at the calcitonin receptor, and 11-fold more potent than at AMY3, measured by cAMP signaling; in binding assays the margin was about 8-fold (Briere 2025). That is why both "8-fold" and "12-fold" turn up in coverage: one is binding, the other signaling, in the same paper. Cagrilintide, run through the same assays, activated all three receptors at comparable strength (Briere 2025), which puts it among the dual amylin and calcitonin receptor agonists, or DACRAs (Alhazmi and le Roux 2026).

    Why would the calcitonin receptor matter? A review counts its engagement among several factors, alongside drug exposure, that may tip satiety toward malaise (Fischer and Borner 2026). Both drugs cut food intake by similar amounts at 24 hours in Lilly's rats, but eloralintide caused less conditioned taste avoidance, a lab marker of feeling unwell (Briere 2025). At the same top dose in obese rats, fat made up 80% of the weight eloralintide removed, against 63% for cagrilintide (Briere 2025). These are rodent studies from eloralintide's owner, and nobody has compared the drugs in people.

    How each got to phase 3

    Novo developed cagrilintide mainly as CagriSema's partner, so its only phase 3 data as a single drug comes from a 302-person arm inside the 3,417-person REDEFINE 1 trial. The dedicated monotherapy trials, RENEW 1 (300 adults without diabetes) and RENEW 2 (330 with type 2 diabetes), started in November 2025 (NCT07220642, NCT07220759). CagriSema itself is waiting on the FDA. In REDEFINE 4 it missed its non-inferiority goal against tirzepatide 15 mg, losing 20.2% against 23.6% at 84 weeks regardless of adherence.

    Eloralintide went from a 263-person phase 2 trial in The Lancet straight into phase 3, and Lilly built its own combination, EloraTZP, with tirzepatide. In a 48-week phase 2b trial in 367 adults with type 2 diabetes, the top pairing tested lost 23.3%, against 14.8% on tirzepatide alone and 3.0% on placebo.

    Program Status on October 24, 2026 Next date
    Cagrilintide alone Phase 3: RENEW 1 and RENEW 2, weight measured at week 64 Primary completion May 2027
    CagriSema Submitted to the FDA in December 2025 (Novo) Decision expected by late 2026
    Eloralintide alone Phase 3: ENLIGHTEN-1 (1,980 people), ENLIGHTEN-2 (1,035 with type 2 diabetes), ENLIGHTEN-3 (800, sleep apnea), ENLIGHTEN-4 (900, knee osteoarthritis), ENLIGHTEN-6 (900 on a weekly incretin) First primary completion January 2028 (ENLIGHTEN-2), the rest by June 2028
    EloraTZP Phase 3 registered AMPLIFY-2 starts November 2026 and AMPLIFY-1 December 2026; both list primary completion in October 2029

    With ENLIGHTEN finishing in 2028, we doubt an eloralintide approval comes before 2029. That is our reading of the registry, not a company forecast. Novo's September 2025 announcement gave no filing date for cagrilintide alone.

    Weight loss, trial by trial

    Trial Population Length Dose tested Loss vs placebo Estimand Caveat
    Eloralintide phase 2 (Lilly) 263 US adults without diabetes, mean BMI 39.1, 78% women (Billings 2025) 48 weeks 9 mg 20.1% vs 0.4% Efficacy: as if all stayed on drug 54 people in the arm
    EloraTZP phase 2b, eloralintide alone (Lilly) 367 adults with type 2 diabetes 48 weeks 6 mg 12.3% vs 3.0% Efficacy One arm of a combination trial
    REDEFINE 1 (Novo) 302 adults without diabetes; trial mean BMI 37.9 (post hoc) 68 weeks 2.4 mg 11.8% vs 2.3%; 11.5% vs 3.0% counting everyone Trial product; treatment policy Component arm
    Cagrilintide phase 2 (Lau 2021) 706 adults without diabetes 26 weeks 4.5 mg 10.8% vs 3.0% Trial product 2.4 mg: 9.5%, registry mean (NCT03856047)

    On estimands, the closest pair is the 9 mg eloralintide arm against REDEFINE 1's cagrilintide arm, since both ask what happens when people keep taking the drug. Subtract placebo and it is 19.7 points against 9.5, a 10.2-point gap. On design, the better match is the eloralintide arm that stepped up through 3 and 6 mg, because REDEFINE 1 escalated too. It lost 16.4% against 0.4%, or 16.0 points against 9.5, a 6.5-point gap. The arm that lost the most and the best-tolerated arm were different arms.

    Side effects and the starting dose

    Eloralintide's posted phase 2 results show how much the dosing schedule mattered, though each arm was small (NCT06230523):

    Eloralintide arm (people) Nausea Vomiting Fatigue
    Placebo (53) 13% 0% 11%
    1 mg (28) 11% 0% 0%
    3 mg (24) 13% 0% 13%
    6 mg from the first dose (28) 64% 25% 29%
    9 mg from the first dose (54) 33% 11% 43%
    6 mg, then 9 mg (24) 54% 17% 46%
    3 mg, 6 mg, then 9 mg (52) 25% 2% 21%

    The arm started at 6 mg fared worst. The pattern is messy, though: the arm started at 9 mg reported less nausea than either arm that began at 6 mg. In the arm escalated through 3 and 6 mg to 9 mg, one in four reported nausea and one of 52 vomited.

    Fatigue sets eloralintide apart (Panou 2026): the phase 2 results posted on ClinicalTrials.gov show 43% on fixed 9 mg against 11% on placebo, while cagrilintide in its phase 2 trial logged 9.8% at 2.4 mg and 19.8% at 4.5 mg, against 3.0% on placebo. A 2026 review counts about 10% stopping eloralintide for adverse events in phase 2, and 8% to 21% across its early trials (Alhazmi and le Roux 2026), though only 6 of 210 left the study for that reason, against 2 of 53 on placebo.

    Cagrilintide was always escalated: over up to 6 weeks in phase 2 and 16 weeks in REDEFINE 1 (Lau 2021, NCT05567796). In phase 2, nausea ranged from 20% at 0.3 mg to 47% at 4.5 mg, against 18% on placebo, with 31% at 2.4 mg (NCT03856047). In REDEFINE 1, about 24% of people on cagrilintide reported nausea, 54% had a gastrointestinal event, and nausea made 1.0% stop for good, against 0.1% on placebo.

    So does selectivity buy gentler side effects? These trials cannot say. Eloralintide arms that began at 6 mg had more nausea than any reported cagrilintide arm, while the eloralintide arm stepped up over eight weeks looked broadly similar. In the data we have, the schedule matters at least as much as the receptor profile.

    Neither drug appears to raise heart rate. On 12 mg of eloralintide, pulse fell 14.4 beats a minute over 12 weeks against 3.4 on placebo, without symptomatic bradycardia (Bhattachar 2026). In phase 2, bradycardia was logged in 3 of 28, 3 of 54 and 3 of 52 people on three higher-dose arms and in no one on placebo. Zealand researchers call a modest pulse drop consistent with cagrilintide's profile (Brændholt Olsen 2026), unlike GLP-1 drugs, which raise heart rate (Sigalov and Frishman 2026).

    Mood is the other signal to watch. The 12-week phase 1b study logged mood events in four people on 6 or 12 mg, one a persistent depressive disorder. The three of them taking 12 mg came off treatment and had recovered within 2 to 4 days (Bhattachar 2026). ENLIGHTEN should clarify both signals.

    Why 20.1% against 11.8% is not a fair fight

    The two headline numbers differ in more than the drug:

    1. One is phase 2 and the other phase 3. The 9 mg eloralintide arm had 54 people, and its 95% confidence interval ran from 17.5% to 22.7% (Billings 2025). Small arms swing, so the true effect could sit anywhere in that range.
    2. The placebo groups behaved differently. Eloralintide's lost 0.4%. REDEFINE 1's lost 2.3% to 3.0%, with lifestyle support in every arm (Garvey 2025).
    3. Different people enrolled. The eloralintide trial was 78% women, against about 68% in REDEFINE 1, where CagriSema's average loss was 22.7% (post hoc). That mix matters: women on CagriSema lost 25.0% in a post hoc analysis (Pharmacy Times).
    4. The doses were picked differently. Lilly's phase 2 hunted for eloralintide's best dose. With semaglutide, 2.4 mg and 4.5 mg of cagrilintide gave the same 7.4-point gain over placebo in phase 1b (Enebo 2021), and Novo carried 2.4 mg forward. Alone, 4.5 mg did better in phase 2, 10.8% against 9.5% at 26 weeks.
    5. The clocks differ. Week 48 and week 68 are different points on a weight curve.

    Our read: eloralintide is probably the stronger amylin drug on its own, but nobody can say by how much. The fairest test short of a head-to-head will come from RENEW 1 and ENLIGHTEN-1, which both weigh people against placebo at week 64 (NCT07220642, NCT07321886). For more, see our amylin analogs overview, eloralintide phase 2 review and eloralintide vs retatrutide, plus two other amylin drugs, petrelintide and amycretin.

    Sources

    Frequently asked

    Its best published result is higher: 20.1% at 48 weeks in phase 2, against 11.8% at 68 weeks for cagrilintide alone in phase 3. The trials differ in phase, size, placebo response and dose selection, and no trial has compared them directly.

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    BioChonchResearch editorial

    Evidence notes from published research and trial registries. Educational information, not medical advice.