Cagrilintide

Wellness

Also known as: CagriSema, Cagrilintide + Semaglutide, AM833, Dual Amylin/Calcitonin Receptor Agonist

Emerging Research

What is Cagrilintide?

A long-acting amylin analog being developed by Novo Nordisk. Most significant as the amylin component of CagriSema — a fixed-dose weekly injection combining cagrilintide 2.4mg with semaglutide 2.4mg. Phase 3 REDEFINE trials published in the New England Journal of Medicine (June 2025) showed mean weight loss of over 20%, among the highest ever recorded for a pharmacological intervention. FDA review expected in 2026.

How it works

Cagrilintide is a dual amylin and calcitonin receptor agonist. Amylin is a peptide hormone co-secreted with insulin from pancreatic beta cells; it complements GLP-1 by suppressing post-meal glucagon, slowing gastric emptying, and — crucially — acting directly on appetite-regulating centers in the hypothalamus and brainstem through a distinct receptor pathway. Combining cagrilintide with semaglutide (a GLP-1 receptor agonist) targets two complementary but non-overlapping appetite circuits simultaneously, which may explain the additive weight loss observed beyond either drug alone.

What marketers claim

  • better than Ozempic or Wegovy
  • permanent weight loss with no rebound
  • approved and available now
  • works without diet or exercise

What evidence supports

  • REDEFINE 1 (NEJM, June 2025, n=3,417): CagriSema produced mean body weight reduction of 20.4% vs 3.0% placebo at week 68 — 60% of participants achieved ≥20% weight loss, 23% achieved ≥30%
  • REDEFINE 2 (NEJM, June 2025, n=1,206 with type 2 diabetes): 13.7% weight reduction vs 3.4% placebo; 73.5% reached HbA1c ≤6.5% vs 15.9% with placebo
  • significantly improved systolic blood pressure, waist circumference, and lipid levels in both trials
  • FDA review of CagriSema submission expected in 2026 — not yet approved
  • Phase 3 data represents highest weight loss ever recorded in a pharmacological obesity trial at the 20%+ benchmark

Research evidence

Key studies on Cagrilintide, summarized in plain language. This is not an exhaustive list — it highlights the most relevant findings.

Coadministered cagrilintide and semaglutide in adults with overweight or obesity (REDEFINE 1)

2025Randomized Controlled Trialn = 3,417 adults with BMI ≥30 or ≥27 with comorbidities (without type 2 diabetes)

Finding: Mean body weight reduction of 20.4% with CagriSema vs 3.0% with placebo at week 68. 60% of participants achieved ≥20% weight loss; 23% achieved ≥30%. Significant improvements in blood pressure, waist circumference, lipids, and cardiometabolic markers. 88% of participants with prediabetes at baseline returned to normoglycemia.

Limitation: Excluded patients with type 2 diabetes. Novo Nordisk-sponsored. GI side effects were common and led to some discontinuations. Trial product estimand (idealized adherence) vs. treatment policy estimand showed different point estimates.

Cagrilintide–semaglutide in adults with overweight or obesity and type 2 diabetes (REDEFINE 2)

2025Randomized Controlled Trialn = 1,206 adults with type 2 diabetes and BMI ≥27

Finding: Mean body weight reduction of 13.7% with CagriSema vs 3.4% with placebo at week 68. 73.5% of CagriSema participants reached HbA1c ≤6.5% vs 15.9% placebo. Significant improvements in glycemic control across all measured endpoints.

Limitation: Weight loss was less pronounced in the T2D population (13.7%) than in REDEFINE 1 (20.4%), likely due to metabolic differences. Industry-sponsored. Long-term cardiovascular outcome data is pending.

Best for

patients with obesity (BMI ≥30, or ≥27 with comorbidity) who have not achieved adequate response with GLP-1 monotherapy — under physician supervisiontype 2 diabetes with obesity requiring dual glycemic and weight management

What to expect

Realistic timeline based on available research. Individual results vary.

Month 1–3

Dose escalation phase. Nausea and GI effects most common. Initial appetite suppression begins. Weight loss of 3–5% typical in this period.

Month 3–6

Approaching maintenance dose. Significant appetite reduction. In REDEFINE 1, meaningful weight loss separation from placebo emerged clearly by week 20.

Month 6–12

Continued weight loss. By week 68 (approximately 15–16 months), REDEFINE 1 showed the 20.4% mean reduction. Blood glucose, lipids, and blood pressure improvements also measurable.

After stopping

As with semaglutide alone, weight regain is expected — consistent with obesity being a chronic condition. Long-term maintenance therapy is likely necessary to sustain results.

Safety notes & concerns

Full safety guide →
  • CagriSema is not yet FDA or EMA approved — currently accessible only through clinical trials or off-label compounding
  • GI side effects (nausea, vomiting, diarrhea) are consistent with the semaglutide component and were common during dose escalation
  • weight regain upon discontinuation is expected — as with all GLP-1 class drugs, CagriSema likely requires long-term use to maintain results
  • cagrilintide monotherapy has less efficacy data than the combination — the bulk of the evidence is for CagriSema together
  • calcitonin receptor agonism raises theoretical bone metabolism questions with long-term use — under active investigation
  • cost, access, and insurance coverage will be major factors upon approval
  • long-term cardiovascular outcome data for CagriSema is not yet available

Pairs well with

structured diet and adequate protein intake to preserve muscle mass during weight lossresistance training (critical to minimize lean mass loss alongside rapid fat loss)regular monitoring of HbA1c, lipids, blood pressure, and bone markers

Use caution with

other GLP-1 receptor agonists (the semaglutide component overlaps)personal or family history of medullary thyroid carcinoma or MEN2 (shared contraindication with semaglutide component)history of pancreatitisdo not self-administer — physician supervision is essential for titration and monitoring

Frequently asked questions

What is CagriSema and is it available?

CagriSema is a fixed-dose combination of cagrilintide 2.4mg and semaglutide 2.4mg in a single once-weekly injection, developed by Novo Nordisk. As of May 2026, it is not yet FDA or EMA approved. Novo Nordisk filed for FDA approval in late 2025, with review expected in 2026. It is not currently available as a standard prescription.

How does cagrilintide differ from semaglutide?

They target different receptor systems. Semaglutide is a GLP-1 receptor agonist. Cagrilintide is a dual amylin and calcitonin receptor agonist. Amylin regulates appetite through a different brain pathway than GLP-1, and the two signals appear to have complementary rather than redundant mechanisms — explaining why the combination produces greater weight loss than either drug alone.

Is 20% weight loss really possible with CagriSema?

Yes — the REDEFINE 1 trial published in the NEJM (June 2025) showed a mean body weight reduction of 20.4% vs 3.0% placebo at week 68, with 60% of participants achieving ≥20% and 23% achieving ≥30%. These are the largest weight reductions ever reported in a randomized trial of an obesity medication, placing CagriSema above tirzepatide and retatrutide on this metric.

How does CagriSema compare to tirzepatide and retatrutide?

By mean weight loss in phase 3 trials: retatrutide (early phase 2 data) showed ~24%, CagriSema ~20.4%, tirzepatide ~22.5% at highest dose, semaglutide ~15%. These trials used different populations and durations, so direct comparisons require caution. CagriSema is the only one targeting the amylin pathway — a mechanistically distinct approach from the GIP/GLP-1 class.

Related wellness peptides

🧪

Take the Peptide Quiz

Get personalized recommendations

🔬

Stack Builder

Build a routine with Cagrilintide

Last updated: 2026-05-13

Medical Disclaimer

The information on this site is for educational and informational purposes only. It is not intended as medical advice and should not be used to diagnose, treat, or prevent any condition. Always consult with a qualified healthcare professional before starting any new supplement, peptide, or treatment protocol.