IN PHASE 3 TRIALS

Cagrilintide

Novo Nordisk's long-acting amylin analog. The not-quite-a-GLP-1 weight-loss peptide that works through a different appetite hormone, and the partner peptide in the CagriSema combination.

The 30-second read

Cagrilintide is a long-acting synthetic version of amylin, a hormone your pancreas releases alongside insulin every time you eat. Amylin slows stomach emptying, signals fullness to the brain, and reduces post-meal glucagon. Cagrilintide does the same things, with a half-life long enough to support once-weekly dosing. As monotherapy in Phase 2, the highest dose produced about 10% weight loss over 26 weeks. Novo Nordisk's bigger play is the combination with semaglutide, called CagriSema, which is in Phase 3 for weight management. Cagrilintide is not currently FDA-approved as monotherapy. The combination story is the one that's likely to reach the U.S. market first.

Why this peptide is on people's radar

Amylin has been on metabolic-medicine's mind for decades. Your pancreas co-secretes it with insulin, and it has its own clean job: telling the brain you've eaten, slowing stomach emptying, suppressing glucagon. Pramlintide (Symlin) was the first amylin analog FDA-approved, in 2005, for diabetes adjunctive therapy. It works, but it requires multiple daily injections and never broke through commercially. Cagrilintide solves the inconvenience problem with engineering: a fatty-acid modification that extends the half-life enough to support once-weekly dosing.

Where it gets interesting is the combination story. GLP-1 drugs (semaglutide, tirzepatide) act on appetite primarily through one set of receptors. Amylin acts through different receptors. In theory, combining them stacks two complementary appetite-suppressing mechanisms without needing a higher dose of either. Novo Nordisk has been developing the cagrilintide + semaglutide combination, branded CagriSema, as their next-generation weight-loss product. The Phase 3 REDEFINE trial program reported in late 2024 / 2025 produced about 22.7% weight loss in REDEFINE-1, which was below Novo's previously-guided expectations. The data is still meaningful, that's a real number. It just wasn't the killer Novo had hoped for relative to tirzepatide.

For the U.S. market, cagrilintide as monotherapy is unlikely to be a major story. The CagriSema combination is the clinical-development path that matters, and that's where the conversation lives.

What people are usually trying to do with it

People reading about cagrilintide are usually focused on:

  • Following the next-generation weight-loss drug landscape after semaglutide and tirzepatide
  • Understanding the CagriSema combination story (the more clinically advanced path)
  • Learning about appetite-suppression mechanisms beyond GLP-1
  • Evaluating whether amylin-based therapy adds anything meaningful for them
  • Tracking Novo Nordisk's competitive response to Eli Lilly's tirzepatide and retatrutide

What the science actually shows

Cagrilintide has rigorous Phase 2 data and ongoing Phase 3 development as part of CagriSema. Plain-English summary:

Phase 2 monotherapy weight loss

The Phase 2 trial of cagrilintide monotherapy reported up to ~10.8% mean weight loss at the highest dose (4.5 mg weekly) over 26 weeks in adults with overweight or obesity. Modest compared to semaglutide; meaningful in absolute terms.1

Combination with semaglutide (CagriSema)

The Phase 1b/2 combination data showed greater weight loss with cagrilintide + semaglutide than either alone, supporting the additive-mechanism hypothesis and triggering Phase 3.2

REDEFINE Phase 3 program

REDEFINE-1 reported about 22.7% mean weight loss with CagriSema in adults with overweight or obesity over 68 weeks, meaningful weight loss, but below Novo's previously-guided expectations of around 25%.3

Mechanism, amylin pathway

Cagrilintide activates amylin and calcitonin receptors, slowing gastric emptying, reducing post-meal glucagon, and signaling satiety in the brain, all through a different pathway than GLP-1 drugs.4

What hasn't been demonstrated

FDA approval for any indication. That cagrilintide monotherapy will be developed for U.S. market (Novo's focus is on the CagriSema combination). Long-term cardiovascular outcomes. Direct head-to-head comparison with tirzepatide.

The honest read

What's solid:

The amylin pathway is real, well-characterized, and offers a complementary mechanism to GLP-1. Cagrilintide's once-weekly profile is a meaningful improvement over earlier amylin analogs. The CagriSema combination data shows the combination produces more weight loss than semaglutide alone.

What's still being worked out:

FDA approval timing. The REDEFINE-1 readout disappointed Novo's stock and shifted expectations. CagriSema is real but not the leap-ahead the company had previewed. How CagriSema will be positioned against tirzepatide (which produced 22.5% in SURMOUNT-1 and 20.2% in the head-to-head SURMOUNT-5) and against retatrutide (24%+ in Phase 2/3) is still being worked out.

What's hyped beyond the evidence:

Treating cagrilintide as already available. Treating CagriSema as available, it isn't, as of May 2026. "Compounded cagrilintide" or "compounded CagriSema" being marketed online is not the FDA-approved drug (which doesn't exist yet) and isn't operating under any manufacturing oversight. The dual-mechanism story is a real biological idea but hasn't yet translated into the dramatic outperformance some commentators projected.

Things to know if you're looking into it

  • Investigational status: cagrilintide is in Phase 3 development as part of the CagriSema combination. It is not FDA-approved. The legitimate way to access it is through clinical trial enrollment.
  • The bigger story is CagriSema: Novo's primary clinical development path is the combination with semaglutide. CagriSema explainer →
  • Different mechanism than GLP-1s: cagrilintide acts on amylin receptors, not GLP-1 receptors. The two mechanisms are complementary rather than overlapping, which is the rationale for combining them.
  • How it would be used: a once-weekly subcutaneous injection. The half-life is engineered to support that dosing schedule.
  • Compounded versions are not the drug: any product marketed as "compounded cagrilintide" isn't operating under FDA manufacturing oversight and isn't the same as the investigational product Novo Nordisk is developing.
  • Healthcare provider involvement: not really an option for cagrilintide right now. Outside clinical trial enrollment, there's no legitimate clinical access pathway.
  • Specific dosing schedule, mechanism, and trial detail: all in the "Want to go deeper?" section below.

Reconstitution & dose calculator

Cagrilintide is investigational — there is no FDA-approved version to reconstitute. The only legitimate access is through a clinical trial, where dosing is managed by the study team. Any product sold as "cagrilintide" outside a trial is not the FDA-approved drug and isn't under manufacturing oversight. The numbers below reflect the once-weekly, slowly-titrated schedule used in Novo Nordisk's trials, and exist only to explain the reconstitution math — not as a recommendation to use it. Educational reference only.
Trial start dose
0.3 mg/week
Titration starts low to limit nausea
Top studied dose
2.4–4.5 mg/week
2.4 mg in CagriSema; 4.5 mg monotherapy Phase 2
Cadence
Once weekly
~7-day half-life; steady state ~5 weeks
Vial size
10 mg
The size this peptide usually ships in
mL
2 mL into a 10 mg vial gives 5 mg/mL. That keeps the whole titration range on a single syringe — a 0.3 mg start is a 6-unit draw, and a 4.5 mg top dose is a 90-unit draw (just under the 100-unit line). Less water means a higher concentration and a smaller draw.
mg
Once-weekly subcutaneous injection. In trials the dose is stepped up slowly (roughly 0.3 → 0.6 → 1.2 → 2.4 → 4.5 mg) about every 4 weeks to let the gut adjust. Enter the step you're modeling.
Concentration
5.00 mg/mL
Per dose
0.060 mL
6.0 units on insulin syringe
Doses per vial
~33
~33 weeks of weekly dosing

How to think about Cagrilintide dosing

It's a titration drug, not a fixed dose. Like the GLP-1 weight-loss peptides, cagrilintide is stepped up slowly rather than started at a target dose. Trials moved roughly 0.3 → 0.6 → 1.2 → 2.4 → 4.5 mg weekly, holding each step about four weeks. The slow ramp exists to keep nausea and vomiting manageable, since amylin side effects track with dose and with how fast you climb.

The vial math at a glance (10 mg + 2 mL water = 5 mg/mL):

  • 0.3 mg → 0.06 mL, a 6-unit draw
  • 2.4 mg (the CagriSema dose) → 0.48 mL, a 48-unit draw
  • 4.5 mg (top monotherapy dose) → 0.90 mL, a 90-unit draw — nearly a full syringe
  • Because a single vial spans many weekly doses, storage and sterility over time matter more than for a one-and-done vial

Once weekly, same day each week. The ~7-day half-life is what makes weekly dosing work; steady state takes about five weeks, so effects (and side effects) build over the first month or so rather than landing all at once.

The combination context matters. Novo's actual product is CagriSema, where 2.4 mg cagrilintide is paired with semaglutide. On its own, cagrilintide's weight-loss effect is more modest than a GLP-1. If you're reading about big REDEFINE numbers, those are the combination, not cagrilintide alone.

Watch for: nausea, vomiting, decreased appetite, and constipation — most prominent while stepping the dose up. These are the same gastrointestinal effects seen across amylin and GLP-1 drugs.

The honest read. This calculator does reconstitution arithmetic; it doesn't turn an investigational drug into something with an established at-home protocol. There isn't one. The only setting with real dosing oversight for cagrilintide is a clinical trial, and that's worth remembering before treating any of these numbers as a plan.

For educational and research purposes only. This is not medical advice. Cagrilintide is investigational and not FDA-approved as of 2026; the only legitimate access is through clinical-trial enrollment. Products sold as "cagrilintide" or "CagriSema" outside trials are not the FDA-approved drug. Consult a licensed healthcare provider before any health decision.

What people often ask

Is cagrilintide a GLP-1 drug?

No. It's an amylin analog. Different hormone, different receptors. Both are pancreatic-secreted peptides, both reduce appetite, but they work through separate pathways, which is the rationale for combining them in CagriSema.

Is it FDA-approved?

No. Cagrilintide is in Phase 3 development as part of the CagriSema combination. As of May 2026 it is not FDA-approved as monotherapy or in combination.

How does it compare to semaglutide alone?

In Phase 2, monotherapy cagrilintide produced about 10.8% mean weight loss versus semaglutide's ~14.9% in STEP-1. So less effective alone. The combination of the two outperforms either alone, which is the rationale for CagriSema.

How does CagriSema compare to tirzepatide (Zepbound)?

REDEFINE-1 reported ~22.7% weight loss with CagriSema. SURMOUNT-1 reported ~22.5% with tirzepatide. SURMOUNT-5's head-to-head showed tirzepatide outperforming semaglutide alone. CagriSema's numbers are competitive but didn't blow tirzepatide out of the water, which contributed to the Novo stock reaction in late 2024 / early 2025.

What about side effects?

Cagrilintide's side-effect profile is similar to other amylin analogs and to GLP-1 drugs, primarily gastrointestinal (nausea, vomiting). The CagriSema combination has shown a similar profile to semaglutide alone in early data.

How is amylin different from insulin?

They're co-secreted from pancreatic beta cells (so released together when you eat) but they do different things. Insulin lowers blood glucose by signaling tissues to take up sugar. Amylin slows stomach emptying, suppresses glucagon, and signals satiety. Both are part of the post-meal hormonal response.

How can I get it?

Through a clinical trial. ClinicalTrials.gov has the active CagriSema trials searchable. Anything sold as "cagrilintide" or "CagriSema" outside trials isn't the FDA-approved drug.

FDA and regulatory status

Status as of May 5, 2026: Investigational. Not FDA-approved as monotherapy or in combination. Currently in Phase 3 trials primarily as part of the CagriSema combination (REDEFINE program). Novo Nordisk has guided to FDA submission timelines pending full Phase 3 readouts. Status updates land here when they happen.

Want to go deeper? Mechanism, the amylin pathway, dosing, REDEFINE Phase 3 detail, and references.

Background and development

Cagrilintide is a long-acting synthetic analog of amylin (also known as Islet Amyloid Polypeptide or IAPP), a 37-amino-acid peptide hormone co-secreted with insulin from pancreatic beta cells. The molecule is engineered with a fatty-acid modification (similar in concept to the fatty-acid modification on semaglutide) that confers albumin binding and extends plasma half-life enough to support once-weekly dosing. Developed by Novo Nordisk, primarily for use in combination with semaglutide as the CagriSema fixed-dose combination.

Mechanism of action

Amylin and calcitonin receptor activation

Cagrilintide activates amylin receptors (composed of the calcitonin receptor plus RAMPs, receptor activity-modifying proteins). The receptor distribution includes the area postrema in the brain, the gut, and pancreatic alpha cells. Activation produces:

  • Slowed gastric emptying
  • Reduced post-meal glucagon secretion
  • Centrally-mediated satiety signaling
  • Modest reductions in food intake

Why pair with GLP-1 (semaglutide)?

GLP-1 drugs activate GLP-1 receptors. Amylin analogs activate amylin receptors. The two pathways converge on satiety but through different signaling mechanisms, meaning the appetite-suppression effects are additive rather than redundant. This is the rationale behind CagriSema.

Half-life and dosing

Plasma half-life is approximately 7 days, supporting once-weekly subcutaneous administration. Steady-state is reached after roughly 5 weeks of consistent dosing.

The clinical-development program

Phase 2 monotherapy

The cagrilintide monotherapy Phase 2 trial in adults with overweight or obesity reported up to ~10.8% mean weight loss at the 4.5 mg weekly dose over 26 weeks. The Phase 2 supported continued development of the combination program.

CagriSema Phase 1b/2

Combined cagrilintide + semaglutide produced greater weight loss than either alone in early dose-finding studies.

REDEFINE Phase 3 program

The Phase 3 program for CagriSema in chronic weight management. Selected results:

  • REDEFINE-1: ~22.7% mean weight loss in adults with overweight or obesity (without diabetes) over 68 weeks. Below Novo's previously-guided expectations and triggering significant stock-price reaction.
  • REDEFINE-2 and beyond: additional Phase 3 readouts in different patient populations and contexts continue to publish.

Side effects and safety profile

The most common adverse events in trials have been gastrointestinal, nausea, vomiting, decreased appetite, constipation. These are dose-dependent and most prominent during dose escalation.

Discontinuation rates due to adverse events have been broadly comparable to semaglutide.

Long-term safety data continues to accumulate through the REDEFINE program.

References

  1. Lau DCW, Erichsen L, Francisco AM, et al. (2021). "Once-weekly cagrilintide for weight management in people with overweight and obesity: a multicentre, randomised, double-blind, placebo-controlled and active-controlled, dose-finding phase 2 trial." The Lancet, 398(10317), 2160–2172. PubMed
  2. Enebo LB, Berthelsen KK, Kankam M, et al. (2021). "Safety, tolerability, pharmacokinetics, and pharmacodynamics of concomitant administration of multiple doses of cagrilintide with semaglutide 2.4 mg for weight management: a randomised, controlled, phase 1b trial." The Lancet, 397(10286), 1736–1748. PubMed
  3. Novo Nordisk. "REDEFINE-1 Phase 3 results." Press releases and SEC filings, 2024–2025. Novo Nordisk
  4. Hay DL, Chen S, Lutz TA, et al. (2015). "Amylin: pharmacology, physiology, and clinical potential." Pharmacol Rev, 67(3), 564–600. PubMed
  5. ClinicalTrials.gov. REDEFINE program registry. ClinicalTrials.gov
For educational and research purposes only. This is not medical advice. Cagrilintide is investigational, not FDA-approved as of May 2026. Legitimate access is through clinical trials. Compounded versions are not the FDA-approved drug. PeptideLibraryHub is independent and does not sell peptides or accept money from anyone who does.