Cagrilintide

The Cagrilintide evidence base cited here is 10 sources — 4 clinical, 3 preclinical, 1 review. Its strongest evidence is human — 4 clinical studies, most recently 2026 ("CagriSema REIMAGINE 2 Phase 3 Trial Results"). Regulatory status: Not FDA-approved (Phase III).

• Cagrilintide (AM833) is a long-acting amylin analog — a dual amylin and calcitonin receptor agonist — developed by Novo Nordisk for weight management, on its own and combined with semaglutide as 'CagriSema'.
• Reported Phase 3 data for CagriSema describe up to ~22.7% weight loss in obesity (REDEFINE 1) and ~15.7% in type 2 diabetes (REDEFINE 2). These are company/topline-stage figures — confirm against the primary publications before relying on them.
• It is not yet commercially available. Projected approval timing (commonly cited as around 2026) is not confirmed and should be verified.

Cagrilintide is a once-weekly injectable amylin analog. Amylin is a hormone co-secreted with insulin that promotes satiety and slows gastric emptying; cagrilintide is a lipidated, long-acting version engineered to act on both the amylin and calcitonin receptors. Its headline role is as the partner to semaglutide in the combination known as CagriSema, where the two mechanisms together have produced some of the largest non-triple-agonist weight-loss figures reported.

It is still investigational — not commercially available and not FDA-approved. Several of the figures and timelines below come from company-reported or topline-stage data; where that is the case it is flagged, and those numbers should be confirmed against peer-reviewed publications.

Cagrilintide (development code AM833) is a ~4,409 Da, 37-amino-acid amylin analog. It is N-terminally lipidated through a γ-glutamic-acid spacer with a C20 fatty-diacid chain — the same albumin-binding strategy used by long-acting incretin drugs — which gives it a long half-life suited to once-weekly dosing. The peptide is cyclic (disulfide-containing) and C-terminally amidated.

Unlike the GLP-1/GIP/glucagon agonists, cagrilintide works through the amylin pathway, which is why it is complementary to (rather than overlapping with) semaglutide — the rationale behind the CagriSema combination.

There is no approved dosing. The figures below are the doses studied in trials, included for research context only.

• Studied as 2.4 mg once weekly subcutaneously (monotherapy and as the cagrilintide component of CagriSema, paired with semaglutide 2.4 mg)
• Stepwise escalation over ~16 weeks: 0.25 → 0.5 → 1.0 → 1.7 → 2.4 mg, the same titration logic used to limit GI effects with incretin drugs
• In REDEFINE 1, only ~57% of participants reached the maximum 2.4 mg dose — a sign that tolerability gates the top dose for a meaningful share of people

Evening dosing is sometimes used to shift any nausea away from the morning; it can be taken with or without food.

This is the technical detail that sets cagrilintide apart from most research peptides: it is pH-sensitive and will form amyloid fibrils at neutral or alkaline pH, which ruins the product. No commercial formulation exists; the following reflects research handling only.

• Requires an acidic environment (≈ pH 3.5–4.5) for stability. Standard bacteriostatic water (≈ pH 5.5–6) is acceptable only short-term (refrigerated, under ~30 days); for longer stability the solution is acidified to ~pH 4 (e.g. with dilute acetic acid).
• Reconstitute slowly down the vial wall and swirl gently — never shake.
• Inspect every time: any cloudiness, particles, or gel-like texture indicates fibril formation — discard immediately.
• Store at 2–8°C; bring to room temperature ~15–30 minutes before injecting; rotate sites.

The fibril-at-neutral-pH behavior is the single most important handling fact for cagrilintide. If the solution isn't crystal clear, it is not usable.

The profile is dominated by gastrointestinal effects early in titration, consistent with appetite-acting metabolic drugs.

• Common: nausea, vomiting, diarrhea — mostly during dose escalation, easing with time
• Anti-cagrilintide antibodies develop in a large share of patients (reported in the ~46–73% range), but have not been reported to reduce efficacy
• No clinically significant QT-interval prolongation was seen in a dedicated thorough-QT study
• Tolerability limits the top dose for some — only ~57% reached 2.4 mg in REDEFINE 1

• REDEFINE 1 (Phase 3 obesity): CagriSema reported ~22.7% mean weight loss at 68 weeks vs placebo — reported figure, confirm against the NEJM publication.
• REDEFINE 2 (Phase 3, type 2 diabetes + obesity): reported ~15.7% weight loss with a large share reaching HbA1c targets — reported figure, confirm against publication.
• Thorough-QT study: a single higher dose showed no clinically relevant QTc prolongation.
• Foundational PK/pharmacology: Lau et al., J Med Chem 2021 (characterized the lipidated amylin analog and its ~1-week half-life).

REDEFINE-program figures and any 2026 approval timing were reported topline; treat them as provisional until peer-reviewed publication and an actual regulatory decision.

Cagrilintide is investigational and not approved by the FDA or any regulatory agency; it is not commercially available. Commonly cited approval projections (around 2026) are not confirmed. Research-grade cagrilintide is for laboratory research only and is not intended for human use.

All citations link to the original source (PubMed, journal site, or regulatory filing). Independent research database — no vendor influence on what's cited.