Research in plain language
Cagrilintide
What it is
Cagrilintide is a long-acting (once-weekly) synthetic analogue of the gut/pancreatic hormone amylin, developed by Novo Nordisk. In research it is studied as an injectable weight-loss agent, both on its own and combined with semaglutide (the combination is called CagriSema), where it suppresses appetite and reduces body weight. It is investigational and not an approved medicine in these trials.
How studies used it
- Model
- Human, adults with overweight or obesity without diabetes
- Studied for
- Weight management (obesity), dose-finding for cagrilintide alone vs liraglutide vs placebo
- Dose
- Absolute 0.3, 0.6, 1.2, 2.4 or 4.5 mg per week subcutaneous; the trial population required BMI >=30 (or >=27 with a comorbidity) but no mean body weight was reported in the abstract, so a precise mg/kg cannot be derived from the abstract. As a rough reference, 4.5 mg at a typical ~100 kg obesity-trial weight is about 0.045 mg/kg/week.
- Dosing
- Once weekly, with stepwise dose escalation
- Route
- subcutaneous
- Duration
- 26 weeks treatment plus 6-week follow-up
Effects measured: Mean weight loss rose with dose: 6.0% to 10.8% (6.4 to 11.5 kg) across cagrilintide 0.3-4.5 mg vs 3.0% (3.3 kg) with placebo. The top dose (4.5 mg, 10.8% / 11.5 kg) beat the active comparator liraglutide 3.0 mg (9.0% / 9.6 kg).
Side effects: Most common were gastrointestinal events (nausea, constipation, diarrhoea) and injection-site reactions. GI events occurred in 41-63% on cagrilintide vs 32% on placebo; nausea 20-47% vs 18% placebo.
- Model
- Human, adults with overweight/obesity without diabetes (BMI 27.0-39.9)
- Studied for
- CagriSema combination (LABEL: cagrilintide + semaglutide together): safety, tolerability, pharmacokinetics and early weight effect
- Dose
- Cagrilintide escalated 0.16, 0.30, 0.60, 1.2, 2.4 or 4.5 mg per week, each co-given with semaglutide 2.4 mg per week. Absolute per-week doses; mean body weight not reported in the abstract, so a verified mg/kg cannot be calculated from the abstract.
- Dosing
- Once weekly, multiple-ascending dose with co-escalation
- Route
- subcutaneous
- Duration
- Up to 25 weeks total (16 weeks co-escalation, 4 weeks at target dose, 5 weeks follow-up)
Effects measured: At week 20, cagrilintide 2.4 mg + semaglutide 2.4 mg gave 17.1% mean weight loss vs 9.8% for matched placebo; cagrilintide 1.2 mg combo gave 15.7%. The 4.5 mg combo gave 15.4% vs 8.0% placebo. Small early phase 1b cohorts (n=95 exposed).
Side effects: 566 adverse events in 92 participants; about 37% were gastrointestinal disorders, mostly mild to moderate, with similar proportions across dose groups.
- Model
- Human, adults with type 2 diabetes (BMI >=27) on metformin +/- SGLT2 inhibitor
- Studied for
- CagriSema combination (LABEL: cagrilintide + semaglutide) vs each drug alone for glycaemic control and weight in type 2 diabetes
- Dose
- 2.4 mg cagrilintide per week (co-given with 2.4 mg semaglutide per week). Mean baseline body weight was 105.7 kg, so cagrilintide 2.4 mg is about 0.023 mg/kg/week (2.4 / 105.7); the semaglutide component is the same on a per-kg basis.
- Dosing
- Once weekly, escalated to the 2.4 mg target
- Route
- subcutaneous
- Duration
- 32 weeks
Effects measured: Small trial (n=92: 31 CagriSema, 31 semaglutide, 30 cagrilintide). Week-32 weight change: -15.6% (-16.3 kg) CagriSema vs -5.1% (-5.3 kg) semaglutide vs -8.1% (-8.4 kg) cagrilintide. HbA1c change (trial-product estimand): -2.2 points CagriSema, -1.8 semaglutide, -0.9 cagrilintide.
Side effects: Mild/moderate gastrointestinal events most common; no level 2 or 3 hypoglycaemia. Nausea 29% CagriSema vs 16% semaglutide vs 13% cagrilintide; vomiting 10% vs 3% vs 0%. No serious AEs in the CagriSema arm.
- Model
- Human, adults with overweight/obesity without diabetes (REDEFINE 1, phase 3a)
- Studied for
- CagriSema combination (LABEL) vs semaglutide alone vs cagrilintide alone vs placebo for weight management
- Dose
- Cagrilintide 2.4 mg per week (with semaglutide 2.4 mg per week) in the combination arm; monotherapy arms used 2.4 mg of one drug. Mean baseline body weight was 106.9 kg, so cagrilintide 2.4 mg is about 0.022 mg/kg/week (2.4 / 106.9).
- Dosing
- Once weekly, escalated to 2.4 mg of each drug, plus lifestyle intervention
- Route
- subcutaneous
- Duration
- 68 weeks
Effects measured: n=3417. Estimated mean weight change at week 68: -20.4% CagriSema, -14.9% semaglutide alone, -11.5% cagrilintide alone, -3.0% placebo (CagriSema vs placebo difference -17.3 points, P<0.001). Larger trials show cagrilintide alone is weaker than semaglutide alone here.
Side effects: Gastrointestinal adverse events (nausea, vomiting, diarrhoea, constipation, abdominal pain) in 79.6% CagriSema, 73.8% semaglutide, 54.0% cagrilintide, 39.9% placebo; described as mainly transient and mild-to-moderate.
- Model
- Human, adults with overweight/obesity AND type 2 diabetes (REDEFINE 2, phase 3a)
- Studied for
- CagriSema combination (LABEL) vs placebo for weight management in type 2 diabetes
- Dose
- Cagrilintide 2.4 mg per week (with semaglutide 2.4 mg per week). The published mean baseline body weight for this arm was not captured in my verified extraction, so a precise mg/kg is not stated here; at a REDEFINE-typical ~100-107 kg, 2.4 mg is roughly 0.022-0.024 mg/kg/week. Body weight basis not individually confirmed for this trial, so treat the per-kg figure as approximate.
- Dosing
- Once weekly, escalated to 2.4 mg of each drug
- Route
- subcutaneous
- Duration
- 68 weeks
Effects measured: n=1206 across 12 countries. Mean body-weight reduction about 13.7% with CagriSema vs 3.4% with placebo; 73.5% of CagriSema participants reached HbA1c 6.5% or below. Weight loss is smaller than in the non-diabetic REDEFINE 1 population.
Side effects: Gastrointestinal adverse events were the most frequent, consistent with the drug class; specific per-arm rates not captured in this verified extraction.
- Model
- Mouse (wild-type and amylin-receptor knockout)
- Studied for
- Mechanistic study: how cagrilintide lowers body weight, testing brain amylin receptors AMY1R/AMY3R
- Dose
- Cagrilintide 0.3, 3 and 30 nmol/kg per day subcutaneous (per-kg dosing as published); salmon calcitonin 150 nmol/kg as comparator
- Dosing
- Once daily
- Route
- subcutaneous
- Duration
- 21 days (3 weeks)
Effects measured: In wild-type mice cagrilintide reduced body weight (about -3.4 +/- 0.51 g vs vehicle) and cut day-1 food intake by roughly 53% (1.2 g vs 2.7 g vehicle); the appetite effect faded after ~3 days. Fat-mass fell ~7% and lean mass rose ~5% (not statistically significant). Effects were lost in AMY1R/AMY3R knockout mice, showing dependence on those brain receptors.
Side effects: No adverse events reported in this study
How solid the evidence is
Evidence quality is unusually strong for a research peptide because cagrilintide reached large randomised phase 3 trials, but several caveats matter. (1) Human-dose basis: cagrilintide is dosed as a fixed once-weekly absolute amount (most maturely at 2.4 mg), not per kg. I converted to mg/kg only where the paper reported its own mean baseline weight: Frias T2D used 105.7 kg (2.4 mg = ~0.023 mg/kg/wk) and REDEFINE 1 used 106.9 kg (2.4 mg = ~0.022 mg/kg/wk). For the phase 2 monotherapy trial (PMID 34798060) and phase 1b (PMID 33894838) the abstracts did not give a mean weight, so I did NOT fabricate one: I gave the absolute mg + the BMI-defined population and flagged any reference figure as approximate. For REDEFINE 2 I could not confirm that trial's own mean weight in my extraction, so its per-kg figure is explicitly approximate. (2) Sample sizes vary hugely: REDEFINE 1 (n=3417) and REDEFINE 2 (n=1206) are robust; the Frias T2D combo trial is small (n=92) and the phase 1b is very small (n=95) and primarily a safety/PK study, so its weight-loss numbers are exploratory, not confirmatory. (3) Combination vs monotherapy: most of the headline weight loss comes from CagriSema (cagrilintide + semaglutide), which I labelled clearly in every combination entry. Cagrilintide alone is a weaker weight-loss agent than semaglutide alone in head-to-head data (REDEFINE 1: -11.5% cagrilintide vs -14.9% semaglutide), which is an honest limitation for anyone interested in cagrilintide as a standalone. (4) Sponsor funding: every human trial here was Novo Nordisk-funded (the developer), a clear conflict-of-interest consideration. (5) Real-world signal: in the wider REDEFINE/clinical programme CagriSema underperformed early expectations (the non-diabetic phase 3 result of ~20.4% was below the ~25% target Novo Nordisk had guided), and weight loss in the diabetes population (~13.7%) was notably smaller than in non-diabetics, which is a real attenuation worth noting rather than a clean positive. (6) Side effects are consistent and dose/titration-driven: gastrointestinal events (nausea, vomiting, diarrhoea, constipation) are the dominant adverse event across every human trial, rising with the combination (up to ~80% GI events in REDEFINE 1) though mostly mild-to-moderate and transient. (7) The mechanism mouse study (PMID 40609154) is animal-only and shows the appetite effect was short-lived (faded after ~3 days) with non-significant body-composition shifts, so it supports the receptor mechanism but is not efficacy evidence. All six PMIDs, titles, authors, journals and years were verified against PubMed/PMC records, and the key numeric outcomes for the Frias and REDEFINE 1 trials were read directly from the source PDFs (correcting an earlier secondary-source paraphrase that had rounded the Frias weight loss to ~13%; the paper actually reports -15.6% / -16.3 kg).
Sources
- Lau DCW, et al. Once-weekly cagrilintide for weight management in people with overweight and obesity: dose-finding phase 2 trial. Lancet. 2021;398(10317):2160-2172.(PMID 34798060)
- Enebo LB, et al. Safety, tolerability, pharmacokinetics, and pharmacodynamics of multiple doses of cagrilintide with semaglutide 2.4 mg for weight management: phase 1b trial. Lancet. 2021;397(10286):1736-1748.(PMID 33894838)
- Frias JP, et al. Efficacy and safety of co-administered once-weekly cagrilintide 2.4 mg with once-weekly semaglutide 2.4 mg in type 2 diabetes: phase 2 trial. Lancet. 2023;402(10403):720-730.(PMID 37364590)
- Garvey WT, et al. Coadministered Cagrilintide and Semaglutide in Adults with Overweight or Obesity (REDEFINE 1). N Engl J Med. 2025;393(7):635-647.(PMID 40544433)
- Davies MJ, et al. Cagrilintide-Semaglutide in Adults with Overweight or Obesity and Type 2 Diabetes (REDEFINE 2). N Engl J Med. 2025;393(7):648-659.(PMID 40544432)
- Oliveira Carvas A, et al. Cagrilintide lowers bodyweight through brain amylin receptors 1 and 3. EBioMedicine. 2025.(PMID 40609154)
- Apovian CM, et al. (CagriSema and the link between obesity and type 2 diabetes - linked commentary). Lancet. 2023;402(10403):680-682.(PMID 37364591)
Study data, research use only. No established human dosing protocol.