Cagrilintide

What it is

Cagrilintide is an investigational amylin analogue developed by Novo Nordisk. Amylin is a pancreatic hormone co-secreted with insulin after meals and involved in satiety and postprandial physiology. Cagrilintide is engineered to act longer than native amylin, allowing once-weekly dosing in clinical trials^{[1 ,6 ]}.

Chemical structure

Cagrilintide is a long-acting synthetic amylin analogue with molecular formula C194H312N54O59S2 and molecular weight of approximately 4409 g/mol^{[1 ]}. PubChem lists the sequence as XKCNTATCATQRLAEFLRHSSNNFGPILPPTNVGSNTP, reflecting a modified peptide designed for once-weekly clinical development^{[1 ]}.

Development path

The main development path for cagrilintide is obesity and metabolic disease. It has been studied as monotherapy and, more prominently, in fixed-dose combination with semaglutide as CagriSema^{[6 –10 ]}. CagriSema combines cagrilintide’s amylin-based satiety pathway with semaglutide’s GLP-1 receptor agonism. This combination is investigational and should not be treated as approved merely because semaglutide is approved in other branded products^{[2 ,8 –9 ]}.

Mechanism

Mechanistically, cagrilintide is intended to engage amylin-receptor pathways that influence appetite, satiety, and body weight^{[6 –7 ]}. The clinical rationale is additive or complementary weight reduction when paired with GLP-1 receptor agonism^{[7 –9 ]}. This remains a drug-development question rather than a general wellness claim.

When used in clinical trials, cagrilintide has been administered by subcutaneous injection, either alone or in combination with semaglutide^{[6 –9 ]}. These route details describe research protocols and are not dosing guidance. There is no FDA-approved cagrilintide product, no approved cagrilintide label, and no lawful routine prescribing pathway for standalone cagrilintide^{[2 ]}.

Regulatory status

Cagrilintide is not FDA-approved for any indication in the United States. FDA’s GLP-1 compounding safety page states that “retatrutide and cagrilintide cannot be used in compounding under federal law,” and further states that they are not components of FDA-approved drugs and have not been found safe and effective for any condition^{[2 ]}.

Compounding prohibition

That FDA statement is directly relevant to online products marketed as compounded cagrilintide, CagriSema, or “cagri.” A compounded product is not FDA-approved, and an investigational drug substance cannot be made legally available for routine patient use simply by calling it compounded or research-grade^{[2 –4 ]}.

Under section 503A, pharmacy compounders may use a bulk drug substance only if it meets specific statutory conditions, including an applicable USP/NF monograph, being a component of an FDA-approved drug product if no monograph exists, or appearing on FDA’s 503A bulks list^{[3 ]}. Under section 503B, outsourcing facilities may compound from bulk only if the substance appears on the 503B bulks list or the compounded drug is on the shortage list at the relevant time^{[4 ]}. Cagrilintide was not identified on the FDA 503A or 503B bulks lists reviewed for this draft^{[3 –4 ]}.

CagriSema NDA submission

Novo Nordisk submitted a New Drug Application to FDA for CagriSema in December 2025 for chronic weight management in adults with obesity or overweight with at least one weight-related comorbidity, according to Novo’s release reproduced by Drugs.com^{[10 ]}. Submission of an NDA means FDA review is underway; it does not mean the product is approved. Standalone cagrilintide would remain distinct from any future fixed-dose combination approval.

Controlled-substance status

Cagrilintide was not identified in the federal controlled-substance schedules in 21 CFR Part 1308 as reviewed for this draft^{[5 ]}. The central regulatory issue is FDA approval and compounding law, not DEA scheduling.

Date of last regulatory verification: May 6, 2026.

Research summary

Phase 2 monotherapy

Cagrilintide monotherapy was studied in a multicenter, randomized, double-blind, placebo-controlled and active-controlled phase 2 dose-finding trial published in The Lancet in 2021^{[6 ]}. The trial enrolled 906 adults with overweight or obesity without diabetes across 57 sites in 10 countries^{[6 ]}. Weight reductions at 26 weeks were greater with cagrilintide doses from 0.3 mg to 4.5 mg than with placebo; a medicines-awareness summary reported reductions from 6.0% to 10.8% versus 3.0% with placebo, with 4.5 mg cagrilintide showing greater weight reduction than liraglutide 3.0 mg in a comparison not adjusted for multiplicity^{[6 ,11 ]}.

Phase 1b combination — CagriSema introduction

Combination development began with a phase 1b trial of cagrilintide coadministered with semaglutide 2.4 mg^{[7 ]}. Enebo and colleagues conducted a randomized controlled multiple-ascending-dose study in adults with BMI 27.0–39.9 kg/m² who were otherwise healthy^{[7 ]}. The primary endpoint was treatment-emergent adverse events, and exploratory endpoints included body weight, glycemic parameters, and hormone measures^{[7 ]}. This study supported further investigation of the combination but was not an efficacy trial for approval.

REDEFINE 1 — overweight/obesity without diabetes

The REDEFINE 1 trial evaluated coadministered cagrilintide and semaglutide in adults with overweight or obesity without type 2 diabetes^{[8 ]}. Garvey and colleagues published the trial in The New England Journal of Medicine in 2025^{[8 ]}. ADA’s summary of the late-breaking presentation reported weight loss up to 22.7% in adults without diabetes, and the NEJM article provides the primary peer-reviewed source for the efficacy and safety interpretation^{[8 ,12 ]}.

REDEFINE 2 — type 2 diabetes

The REDEFINE 2 trial studied CagriSema in adults with overweight or obesity and type 2 diabetes^{[9 ]}. Davies and colleagues published the trial in The New England Journal of Medicine in 2025^{[9 ]}. ADA’s summary reported weight loss up to 15.7% in adults with type 2 diabetes, while the peer-reviewed article should be used for final endpoint definitions, estimands, and adverse-event interpretation^{[9 ,12 ]}.

REDEFINE 4 — head-to-head with tirzepatide

Novo Nordisk later reported additional company topline phase 3 data. REDEFINE 4 compared CagriSema with tirzepatide in an open-label head-to-head trial and did not meet the primary endpoint of showing noninferiority for weight loss compared with tirzepatide 15 mg at 84 weeks^{[13 ]}. REIMAGINE 2 reported glycemic and weight outcomes in adults with type 2 diabetes inadequately controlled with metformin with or without an SGLT2 inhibitor^{[14 ]}. These company-reported results should be treated as preliminary until full peer-reviewed publications are available.

Where the evidence ends

Overall, cagrilintide has a strong investigational evidence base relative to many research peptides, including a large phase 2 monotherapy trial and peer-reviewed phase 3 CagriSema trials. It remains investigational, and claims should distinguish standalone cagrilintide from the cagrilintide-semaglutide combination.

Public discourse

The U.S. Food and Drug Administration addressed the legality of cagrilintide and retatrutide compounding directly on its GLP-1 compounding safety page^{[2 ]}.

The American Diabetes Association summarized CagriSema findings presented in a late-breaking symposium and published in NEJM^{[12 ]}.

Mike Doustdar, president and CEO of Novo Nordisk, framed CagriSema as a combination of semaglutide with a novel mechanism^{[10 ]}.

Novo Nordisk reported that CagriSema did not meet the head-to-head noninferiority endpoint against tirzepatide in REDEFINE 4^{[13 ]}.

Public discourse reflects the views of the speakers cited and does not represent medical advice or the editorial position of ProPeptideGuide.

Side effects and safety

Cagrilintide has no FDA-approved prescribing information. There is no FDA-reviewed label establishing contraindications, common adverse reactions, drug interactions, pregnancy or lactation safety, long-term monitoring, or risk mitigation for standalone cagrilintide^{[2 ]}.

Trial-level safety signals

In the phase 2 cagrilintide monotherapy trial and combination trials, gastrointestinal adverse events were common, consistent with appetite-regulating peptide therapies^{[6 –9 ]}. Final safety interpretation should use the full trial publications because tolerability depends on dose, escalation schedule, comparator, discontinuation handling, and whether cagrilintide is used alone or with semaglutide.

Combination interpretation

Combination therapy raises additional safety interpretation issues. Semaglutide has an FDA-approved label in other products, but cagrilintide plus semaglutide as CagriSema remains investigational^{[2 ,11 ]}. Safety cannot be inferred by simply adding cagrilintide to an approved semaglutide regimen outside a studied product and protocol.

Compounding-related risks

FDA’s warning that cagrilintide cannot be used in compounding under federal law is also a safety concern^{[2 ]}. Products sold online as cagrilintide, CagriSema, or “cagri” may lack verified identity, sterility, potency, purity, stability, and dosing accuracy.

Long-term safety data are still developing. Completed and ongoing phase 3 programs will inform cardiovascular, metabolic, gallbladder, gastrointestinal, pancreatitis, pregnancy, and durability questions, but no FDA-approved label existed as of this draft.

Available through

Cagrilintide is not currently available through FDA-compliant prescription or compounding channels in the United States. FDA states that cagrilintide cannot be used in compounding under federal law^{[2 ]}.

CagriSema is under FDA review, but it is not approved as of 2026-05-06. ProPeptideGuide does not link to or endorse grey-market vendors, research-chemical sellers, online peptide shops, compounded cagrilintide, or clinics advertising nonapproved cagrilintide or CagriSema access.