Cagrilintide

Cagrilintide is a long-acting, lab-made version of amylin, a hormone the pancreas releases alongside insulin, and is best known for its role in weight loss, usually paired with semaglutide as CagriSema. It works by increasing fullness and slowing digestion, the same way natural amylin does. Given as a once-weekly injection under the skin, it is not FDA-approved for any use on its own — it remains investigational, most studied as part of the CagriSema combination.

Cagrilintide, an amylin analog, has been studied for weight loss — usually combined with semaglutide. In a large Phase 3 trial (REDEFINE 1) in adults with overweight or obesity without diabetes, cagrilintide plus semaglutide was associated with about 20.4% average weight reduction over 68 weeks versus about 3.0% on placebo; a cagrilintide-alone arm reached about 11.8% versus 2.3% on placebo. Gastrointestinal side effects such as nausea were common. Novo Nordisk has since begun a dedicated Phase 3 program testing cagrilintide on its own, called RENEW.

Not FDA-approved for any indication as of the last review (2026-07-17). Cagrilintide monotherapy and the cagrilintide-semaglutide fixed-dose combination (CagriSema) are investigational — Novo Nordisk advanced CagriSema through the Phase 3a REDEFINE 1 trial (adults without diabetes) and REDEFINE 2 trial (adults with type 2 diabetes), with results published in NEJM in 2025.[⁴][⁵] Novo Nordisk submitted a New Drug Application (NDA) to the FDA for CagriSema in December 2025, based on REDEFINE 1 and 2; a first FDA decision is expected late 2026. Cagrilintide monotherapy is itself now in Phase 3 — the dedicated RENEW program (NCT07220642, NCT07220759) began November 2025.[⁷] Cagrilintide is not currently available through approved pharmaceutical supply chains; research-peptide and unregulated GLP-1-cluster supply chains have begun making cagrilintide and CagriSema-like formulations available outside the FDA-recognized supply chain. Not DEA-scheduled. WADA status: cagrilintide is not explicitly named on the 2026 Prohibited List as of last review; the broader GLP-1 ra / amylin-axis class is not currently a WADA-targeted category, though this may change as obesity pharmacotherapy expands.

Cagrilintide is not FDA-approved for any indication and is investigational; it is not available through approved pharmaceutical supply chains. VialWise is a research and educational reference, not medical advice — consult a licensed professional.

⚠️ For research and educational purposes only. Cagrilintide (alone or in the CagriSema fixed-dose combination with semaglutide) is not currently FDA-approved for any indication. Novo Nordisk has completed Phase 3a clinical trials with results published in NEJM in 2025;[⁴][⁵] regulatory submission and approval timelines depend on Novo Nordisk strategy. Cagrilintide is not currently available through approved pharmaceutical supply chains. Research-peptide and unregulated GLP-1-cluster supply chains have begun making it available outside the FDA-recognized supply chain. Information in this entry is informational, not medical advice. Always confirm dose calculations with the in-app calculator and consult appropriate professional guidance before any protocol decisions.

⚠️ The CagriSema (cagrilintide + semaglutide) Phase 3a results are among the largest weight-loss results in published obesity-pharmacotherapy literature — but Phase 3 results in REDEFINE 1 (20.4%) were modestly below the early-trial expectations (~25%) that drove Novo Nordisk stock volatility in late 2024. Two key data points anchor cagrilintide's clinical relevance: - REDEFINE 1 (Garvey 2025 NEJM): Phase 3a 68-week trial in 3,417 adults with overweight or obesity without diabetes. Mean body-weight reduction with cagrilintide-semaglutide + = −20.4% vs placebo −3.0% (treatment difference −17.3 percentage points, p<0.001).[⁴] - REDEFINE 2 (Davies 2025 NEJM): Phase 3a 68-week trial in 1,206 adults with overweight or obesity and type 2 diabetes. Mean body-weight reduction with cagrilintide-semaglutide = −13.7% vs placebo −3.4% (treatment difference −10.4 percentage points, p<0.001). 73.5% of cagrilintide-semaglutide patients achieved HbA1c ≤6.5% vs 15.9% placebo.[⁵] Context: Novo Nordisk's published Phase 1b expectations (Enebo 2021, Lancet) reported 17.1% weight loss at 20 weeks with the cagrilintide + semaglutide combination — a result that anchored market expectations of ~25%+ weight loss at the 68-week Phase 3 timepoint.[³] The actual REDEFINE 1 Phase 3 result of 20.4% met the regulatory primary-endpoint significance threshold but was below the most optimistic projections.

⚠️ Cagrilintide is dosed in milligrams (mg), not micrograms — same as the GLP-1 ra family. Unlike the GHS-axis peptide entries in the library that dose in mcg, cagrilintide doses are typically per weekly injection (the dose used in the REDEFINE 1/2 Phase 3a trials). Cagrilintide is supplied in research-peptide / unregulated GLP-1-cluster supply chains in formats ranging vials. Always verify the units field shows "mg" before entering the dose in the Vialwise calculator. Same mg-scale dosing convention as Semaglutide, Tirzepatide, Liraglutide, Retatrutide, and Exenatide.

⚠️ Cagrilintide is mechanistically distinct from the GLP-1 ra family — but the two mechanisms are additive on weight loss. The GLP-1 ra family (Semaglutide, Tirzepatide, Liraglutide, Retatrutide, Exenatide) act primarily at the GLP-1 receptor (Tirzepatide also at the GIP receptor; Retatrutide also at the glucagon receptor) — producing satiety, delayed gastric emptying, and improved glycemic control. Cagrilintide acts at the amylin and calcitonin receptor family — producing complementary satiety signaling and gastric emptying delay through a distinct receptor pathway. The Phase 1b Enebo 2021 and Phase 3 Garvey 2025 / Davies 2025 trials established that the cagrilintide + semaglutide combination produces additive (super-additive in some metrics) weight loss compared to either compound alone.[³][⁴][⁵] CagriSema is the clinical-development manifestation of this additive-mechanism hypothesis.

⚠️ The gastrointestinal-adverse-event burden of CagriSema is substantial. Per the REDEFINE 1 Phase 3a results, gastrointestinal adverse events affected 79.6% of patients in the cagrilintide-semaglutide group vs 39.9% in the placebo group — including nausea, vomiting, diarrhea, constipation, abdominal pain.[⁴] REDEFINE 2 reported 72.5% GI adverse events vs 34.4% placebo.[⁵] Most events were transient and mild-to-moderate in severity. The GI burden of CagriSema is higher than for semaglutide monotherapy — the additive-mechanism benefit on weight loss comes with an additive GI adverse-event signal that is the dominant tolerability concern in clinical practice.

According to PubMed-indexed research, cagrilintide is a long-acting amylin analogue developed by Novo Nordisk under development code NNC0174-0833 (also AM 833 in some publications) for chronic weight management.[¹][²] Cagrilintide is structurally derived from human amylin — the 37-amino-acid pancreatic-β-cell co-secreted hormone with insulin — with modifications conferring once-weekly subcutaneous half-life via fatty-acid acylation (similar engineering approach to once-weekly semaglutide and other long-acting peptide therapeutics). Cagrilintide is a non-selective agonist at the amylin and calcitonin receptor family — primarily mediating central satiety signaling and gastric emptying delay, with mechanism distinct from the GLP-1 ra family (Semaglutide, Tirzepatide, Liraglutide, Retatrutide, Exenatide).

Mechanism. Amylin (also called islet amyloid polypeptide / IAPP) is co-secreted with insulin from pancreatic β-cells in response to nutrient intake. Endogenous amylin signaling is acutely satiety-inducing and slows gastric emptying — complementing insulin's direct glucose-lowering effect with a parallel pathway of post-prandial energy-balance regulation. Cagrilintide is a long-acting synthetic agonist of this pathway — the once-weekly subcutaneous formulation produces sustained amylin-receptor activation, in contrast to the rapid clearance of endogenous amylin (very short half-life in human circulation). The mechanism complements GLP-1 ra-class weight loss effects at the satiety and gastric-emptying axes through a distinct receptor pathway — establishing the rationale for the CagriSema combination.

Cagrilintide monotherapy Phase 2 dose-finding (Lau 2021 Lancet).[²] The Lau 2021 *Lancet* Phase 2 dose-finding trial enrolled 706 adults without diabetes, BMI ≥30 (or ≥27 with hypertension/dyslipidemia), randomized 6:1 to cagrilintide (0.3, 0.6, 1.2, 2.4, or once-weekly SC) or volume-matched placebo, with an active-control arm of liraglutide once-daily SC. Treatment period 26 weeks (including ≤6-week dose-escalation) + 6-week follow-up. Cagrilintide produced dose-dependent weight loss: 6.0–10.8% across doses (vs placebo 3.0%; treatment difference 3.0–7.8 percentage points, p<0.001). Cagrilintide produced significantly greater weight loss than liraglutide (10.8% vs 9.0%, treatment difference 1.8%, p=0.03). Gastrointestinal adverse events were the most common — 41–63% in cagrilintide groups vs 32% placebo, primarily nausea (20–47% vs 18%).[²] This is the foundational Phase 2 cagrilintide-alone clinical-pharmacology citation — it is no longer the most advanced monotherapy evidence; see the REDEFINE 1 cagrilintide-alone arm and the RENEW Phase 3 program below.

Cagrilintide-semaglutide Phase 1b combination (Enebo 2021 Lancet).[³] The Enebo 2021 *Lancet* Phase 1b trial enrolled 96 adults BMI 27.0–39.9 kg/m² without diabetes, randomized 3:1 to cagrilintide (0.16, 0.30, 0.60, 1.2, 2.4, or once-weekly SC) or matched placebo, in combination with once-weekly semaglutide in all groups. Multiple-ascending dose design over 16 weeks of co-escalation + 4 weeks at target dose + 5 weeks follow-up. Mean percentage body-weight reductions at week 20 were greater with cagrilintide + semaglutide (15.7%), cagrilintide + semaglutide (17.1%), and cagrilintide + semaglutide (15.4%) than with placebo + semaglutide (8.0–9.8%). Cagrilintide pharmacokinetics: half-life 159–195 hours, Tmax 24–72 hours, no effect on semaglutide exposure or elimination. The Enebo Phase 1b combination-dose-finding result anchored the selection of cagrilintide + semaglutide as the CagriSema Phase 3 fixed-dose combination.[³]

CagriSema Phase 3a REDEFINE 1 (Garvey 2025 NEJM).[⁴] The Garvey 2025 *New England Journal of Medicine* Phase 3a trial enrolled 3,417 adults with BMI ≥30 (or ≥27 with at least one obesity-related complication) without diabetes, randomized 21:3:3:7 to cagrilintide-semaglutide +, semaglutide alone, cagrilintide alone, or placebo, plus lifestyle interventions for all groups. 68-week treatment duration. Coprimary endpoints: percent change in body weight (treatment-policy estimand) and the proportion of patients achieving ≥5% body-weight reduction. Mean body-weight reduction: cagrilintide-semaglutide −20.4% vs placebo −3.0% (treatment difference −17.3 percentage points, 95% CI −18.1 to −16.6, p<0.001). Weight-loss targets of ≥5%, ≥20%, ≥25%, and ≥30% all favored cagrilintide-semaglutide (p<0.001 for all). Gastrointestinal adverse events affected 79.6% of cagrilintide-semaglutide patients vs 39.9% of placebo patients — mainly transient and mild-to-moderate.[⁴] REDEFINE 1 is the foundational Phase 3 efficacy citation for CagriSema in non-diabetic obesity.

Cagrilintide monotherapy Phase 3 data (REDEFINE 1 cagrilintide-alone arm). REDEFINE 1 also contained a cagrilintide monotherapy arm (n=302), whose 68-week results were presented as a sub-analysis at EASD 2025. In that arm, participants had a mean body-weight reduction of about −11.8% versus −2.3% on placebo (trial-product estimand), with ≥15% weight loss reached by 31.6% of the cagrilintide group versus 4.7% of placebo; on the treatment-policy estimand the figures were −11.5% versus −3.0%, with ≥15% reached by 31.0% versus 5.2%. Nausea-driven discontinuation was 1.0% versus 0.1%. Novo Nordisk described this as the first Phase 3 clinical-trial data for a long-acting amylin analogue monotherapy in obesity. [⁴]

Cagrilintide monotherapy Phase 3 program — RENEW. Following the REDEFINE 1 monotherapy arm, Novo Nordisk advanced cagrilintide alone into a dedicated Phase 3 program. Per ClinicalTrials.gov, two RENEW-tier Phase 3 monotherapy trials both started 2025-11-05 and are ACTIVE, not recruiting: NCT07220642 (cagrilintide for weight management in participants with overweight or obesity, without diabetes; n≈300, primary completion 2027-05-11) and NCT07220759 (the same in participants with overweight or obesity and type 2 diabetes; n≈330, primary completion 2027-05-12).[⁷] Cagrilintide monotherapy is therefore no longer a Phase-2-stage compound, though neither RENEW trial has reported results.

Cagrilintide monotherapy arm in REIMAGINE 2 (Phase 3, type 2 diabetes). REIMAGINE 2 (Buse et al., Lancet Diabetes & Endocrinology 2026; NCT06065540, n=2713) compared CagriSema against semaglutide or cagrilintide in people with type 2 diabetes, and includes a cagrilintide monotherapy arm (n=152) — a second Phase 3 source carrying monotherapy data.[⁶] On the trial's primary endpoint, CagriSema reduced HbA1c by 1.91 percentage points versus 1.75 with semaglutide at week 68 (estimated difference −0.16 pp; 95% CI −0.27 to −0.05; p=0.0035).[⁶]

CagriSema Phase 3a REDEFINE 2 (Davies 2025 NEJM).[⁵] The Davies 2025 *New England Journal of Medicine* Phase 3a parallel trial enrolled 1,206 adults with BMI ≥27, HbA1c 7–10%, and type 2 diabetes, randomized 3:1 to cagrilintide-semaglutide + or placebo, plus lifestyle intervention, for 68 weeks. Mean body-weight reduction: −13.7% with cagrilintide-semaglutide vs −3.4% placebo (treatment difference −10.4 percentage points, p<0.001). Glycemic outcomes: 73.5% of cagrilintide-semaglutide patients achieved HbA1c ≤6.5% vs 15.9% placebo. Gastrointestinal adverse events affected 72.5% of cagrilintide-semaglutide patients vs 34.4% placebo.[⁵] REDEFINE 2 establishes CagriSema's efficacy in the type-2-diabetes-with-overweight-or-obesity population.

Regulatory status (US — current). Cagrilintide is not FDA-approved for any indication. The Phase 3a REDEFINE 1 and REDEFINE 2 results were published in June 2025, and on the strength of those trials Novo Nordisk submitted a New Drug Application (NDA) to the FDA for the cagrilintide-semaglutide combination in December 2025 — an NDA under the 505 pathway, not a Biologics License Application. A first FDA decision is expected late 2026; as of mid-2026 neither cagrilintide nor CagriSema is approved in the US or EU.[⁸] Cagrilintide is not currently available through approved pharmaceutical supply chains. Research-peptide and unregulated GLP-1-cluster supply chains have begun making cagrilintide and CagriSema-like formulations available outside the FDA-recognized supply chain — a regulatory context that parallels the broader unregulated GLP-1 ra supply chain that emerged around semaglutide and tirzepatide compounding-pharmacy and gray-market activity in 2023–2026. Not DEA-scheduled.

Regulatory status (sport — WADA). Cagrilintide is not explicitly named on the 2026 WADA Prohibited List as of last review. The broader GLP-1 ra / amylin-axis class is not currently a WADA-targeted category. Users in regulated sport should verify the current WADA status directly via the WADA Prohibited List and their National Anti-Doping Organization before any use.

Common research interests. Cagrilintide is used in research-community contexts for: - Weight management as part of CagriSema combination (cagrilintide + semaglutide once weekly SC) — the dominant research-community use case, tracking the published REDEFINE 1/2 Phase 3a regimen.[⁴][⁵] - Cagrilintide monotherapy once weekly SC for weight management — secondary research-community use case extrapolating from Lau 2021 Phase 2 data, less commonly reported than the combination.[²] - Adjunct to existing GLP-1 ra therapy — some research-community use reports adding cagrilintide to existing semaglutide or tirzepatide regimens at varying doses to capture the additive amylin-axis effect. The cagrilintide + tirzepatide combination is not directly characterized in published trials but is mechanistically plausible.

Commonly reported

• Nausea — the most common adverse event in cagrilintide and CagriSema trials; affected the majority of cagrilintide-semaglutide patients in REDEFINE 1/2; typically transient and mild-to-moderate; tends to attenuate over the first 4–8 weeks of dose escalation
• Vomiting — secondary GI adverse event; less common than nausea but a substantial driver of treatment discontinuation in some trial subgroups
• Diarrhea — common in REDEFINE 1/2
• Constipation — common; amylin agonist gastric-emptying-delay mechanism contributes
• Abdominal pain — common; usually mild-to-moderate
• Injection-site reactions — typical of subcutaneous peptide injection; less common than the GI adverse events
• Decreased appetite — the intended pharmacological effect; reported as an "adverse event" in some trial classifications when severe
• Hypoglycemia — uncommon as monotherapy; more common when combined with insulin or sulfonylureas in type 2 diabetes (REDEFINE 2 context)
• Fatigue / asthenia — uncommon
• Headache — uncommon
• Long-term safety beyond 68 weeks is not yet established in published Phase 3 evidence. The REDEFINE 1/2 trials are 68-week studies; longer-duration follow-up has not been published.
• Real-world adherence and discontinuation rates for CagriSema in clinical practice are not yet established; the Phase 3 trial setting provides structured dose-escalation support that may not translate to real-world clinical practice.
• The GI burden of CagriSema is higher than for semaglutide monotherapy per the cross-trial comparison of REDEFINE 1/2 vs published semaglutide STEP trial results — the additive-mechanism weight-loss benefit comes with an additive GI adverse-event signal that is the dominant tolerability concern.

Serious

• Severe abdominal pain (concern for acute pancreatitis) — GLP-1 ra-class warning; amylin-agonist combination may carry similar mechanistic concern; immediate medical evaluation warranted
• Severe vomiting causing dehydration or kidney injury — uncommon but reported in GLP-1 ra-class clinical trials; warrants immediate medical evaluation
• Right-upper-quadrant pain (concern for gallbladder disease) — GLP-1 ra-class carries elevated cholelithiasis signal; CagriSema may carry similar mechanistic concern
• Severe hypoglycemia (in patients on concurrent insulin or sulfonylureas) — immediate carbohydrate administration warranted
• Neck lump or persistent neck symptoms (concern for medullary thyroid carcinoma) — GLP-1 ra-class boxed warning; immediate medical evaluation warranted
• Allergic reaction (hives, swelling, difficulty breathing) — extremely rare but warrants immediate medical evaluation
• Severe disordered-eating presentation triggered by the strong appetite-suppression effect — warrants immediate discontinuation and mental-health evaluation

Personal or family history of medullary thyroid carcinoma — GLP-1 ra-class boxed warning; CagriSema likely inherits the same warning given the semaglutide component

Multiple Endocrine Neoplasia syndrome type 2 (MEN-2) — same boxed warning

Pregnancy — contraindicated; embryofetal toxicity data limited for cagrilintide specifically but the broader GLP-1 ra / amylin-axis class is contraindicated in pregnancy

Lactation — no human data; default to contraindicated

Pediatric use — no published pediatric clinical-trial evidence for cagrilintide; not currently being developed for pediatric indications

Active acute pancreatitis or history of pancreatitis — caution per GLP-1 ra-class convention

Severe gastrointestinal disease (severe gastroparesis, gastric outlet obstruction, history of bariatric surgery with altered GI anatomy) — caution given amylin-agonist gastric-emptying-delay mechanism

Active diabetic retinopathy — caution per the GLP-1 ra-class observation of transient diabetic retinopathy worsening early in semaglutide treatment (semaglutide labeling caution)

Regulatory note (US): Cagrilintide is not FDA-approved for any indication as of the entry-publication date. Regulatory submission and approval timeline depend on Novo Nordisk strategy after the published REDEFINE 1/2 results.

Regulatory note (sport): Not explicitly named on the 2026 WADA Prohibited List as of last review. Users in regulated sport should verify directly.

Not DEA-scheduled.

Amylin analogue

A lab-made copy of amylin, a natural hormone released with insulin that slows digestion and increases fullness.

Peptide

A short chain of amino acids, the building blocks of proteins. Many compounds in this library are peptides.

Subcutaneous

An injection into the fatty layer just under the skin, rather than into a muscle or vein.

Investigational

Still being studied and not yet approved by regulators for general use.

Half-life

Roughly how long the body takes to clear half of a dose. A long half-life is why some compounds can be taken only once a week.

1. Novo Nordisk A/S. Cagrilintide (NNC0174-0833 / AM 833) clinical development program, 2016–present. Long-acting amylin analogue developed by Novo Nordisk for chronic weight management. Source for: cagrilintide structural origin (long-acting amylin analogue with fatty-acid acylation conferring once-weekly half-life); the broader amylin-pharmacology context (endogenous amylin co-secreted with insulin; pramlintide as the historical first amylin analogue, FDA-approved as Symlin for adjunct to insulin in type 1 diabetes); the cagrilintide-semaglutide combination development (CagriSema) and REDEFINE 1/2 Phase 3a program rationale.
2. Lau DCW, Erichsen L, Francisco AM, Satylganova A, le Roux CW, McGowan B, Pedersen SD, Pietiläinen KH, Rubino D, Batterham RL. (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 (November 16, 2021).(PMID 34798060 · NCT03856047)
3. Enebo LB, Berthelsen KK, Kankam M, Lund MT, Rubino DM, Satylganova A, Lau DCW. (2021). Safety, tolerability, pharmacokinetics, and pharmacodynamics of concomitant administration of multiple doses of cagrilintide with semaglutide 2· for weight management: a randomised, controlled, phase 1b trial. The Lancet, 397(10286):1736–1748 (April 22, 2021).(PMID 33894838 · NCT03600480)
4. Garvey WT, Blüher M, Osorto Contreras CK, Davies MJ, Winning Lehmann E, Pietiläinen KH, Rubino D, Sbraccia P, Wadden T, Zeuthen N, Wilding JPH, et al. (2025). Coadministered Cagrilintide and Semaglutide in Adults with Overweight or Obesity. The New England Journal of Medicine, 393(7):635–647 (June 22, 2025).(PMID 40544433 · NCT05567796)
5. Davies MJ, Bajaj HS, Broholm C, Eliasen A, Garvey WT, le Roux CW, Lingvay I, Lyndgaard CB, Rosenstock J, Pedersen SD, et al. (2025). Cagrilintide-Semaglutide in Adults with Overweight or Obesity and Type 2 Diabetes. The New England Journal of Medicine, 393(7):648–659 (June 22, 2025).(PMID 40544432 · NCT05394519)
6. Buse JB, et al. (2026). Cagrilintide-semaglutide (CagriSema) versus semaglutide or cagrilintide in people with type 2 diabetes (REIMAGINE 2): a phase 3 study. Lancet Diabetes & Endocrinology, 14(8):662–677.(PMID 42251859 · NCT06065540)
7. ClinicalTrials.gov registry records for the cagrilintide monotherapy Phase 3 (RENEW) programme, sponsor Novo Nordisk A/S: NCT07220642 — Efficacy and Safety of Cagrilintide for Weight Management in Participants With Overweight or Obesity (Phase 3, n≈300, started 2025-11-05, ACTIVE_NOT_RECRUITING, primary completion 2027-05-11); and NCT07220759 — the corresponding trial in Participants With Overweight or Obesity and Type 2 Diabetes (Phase 3, n≈330, started 2025-11-05, ACTIVE_NOT_RECRUITING, primary completion 2027-05-12). Also the source for the newer Phase 1 cagrilintide pharmacokinetics study in hepatic impairment plus absolute bioavailability, NCT05564104 (COMPLETED, primary completion 2024-09-06), whose results are not yet published.(NCT07220642)
8. Drugs.com CagriSema regulatory history — drugs.com/history/cagrisema.html. Source for the current US regulatory status: Novo Nordisk submitted a New Drug Application (NDA) to the FDA for once-weekly CagriSema (cagrilintide + semaglutide) in December 2025, based on REDEFINE 1 and REDEFINE 2, with a first FDA decision expected late 2026; CagriSema is not FDA-approved as of the 2026-07-17 check.

• Semaglutide — discussed together in this entry's stacks section
• Tirzepatide — discussed together in this entry's stacks section
• Liraglutide — discussed together in this entry's stacks section
• Retatrutide — discussed together in this entry's stacks section
• Exenatide — discussed together in this entry's stacks section
• Pramlintide — same mechanism class