Evidence-Based Summary
Three separate questions are often blurred together. (1) Cagrilintide alone: in a 26-week phase 2 trial in adults with obesity, weight fell 6.0% to 10.8% across dose groups versus 3.0% with placebo. (2) Semaglutide alone: approved, with 14.9% average weight loss versus 2.4% for placebo over 68 weeks in STEP 1, plus cardiovascular outcome benefit. (3) The combination, CagriSema: 20.4% versus 3.0% for placebo over 68 weeks in REDEFINE 1. The cleanest direct comparison of all three comes from a small 32-week phase 2 trial in 92 people with type 2 diabetes: weight change was −15.6% with CagriSema, −8.1% with cagrilintide and −5.1% with semaglutide, while HbA1c fell 2.2, 0.9 and 1.8 percentage points. CagriSema beat both single drugs for weight; the published abstract does not report a statistical test of cagrilintide against semaglutide. Neither cagrilintide nor CagriSema is FDA-approved.
Quick Comparison: Cagrilintide vs Semaglutide
A high-level comparison of molecule class, molecular receptor targets, FDA regulatory approvals, and verified clinical programs.
| Feature | Cagrilintide | Semaglutide |
|---|---|---|
| Class | Investigational long-acting amylin analogue | Approved GLP-1 receptor agonist |
| Target receptors | Amylin receptors and calcitonin receptor (nonselective, in cell studies) | GLP-1 receptor |
| How it is given | Once-weekly injection under the skin, alone or with semaglutide, in trials only | Once-weekly injection or daily tablet, depending on product |
| U.S. regulatory status (October 2026) | Not FDA-approved, alone or as CagriSema; FDA says cagrilintide cannot be used in compounding | FDA-approved in several products (Ozempic, Rybelsus, Wegovy) |
| Strongest human evidence | Phase 2 trial alone; phase 3 trials (REDEFINE, REIMAGINE) mainly as part of CagriSema | Phase 3 trials plus cardiovascular and kidney outcome trials |
| Main safety concerns | Gastrointestinal effects, mainly nausea; injection-site reactions | Gastrointestinal effects; label warnings including pancreatitis and gallbladder disease, and a boxed warning based on rodent thyroid C-cell tumors |
| Direct comparison | Phase 2 three-arm trial in type 2 diabetes; REDEFINE 1 and REIMAGINE 2 also had single-drug arms | Same trials |
| WADA status (2026 List) | Not named; as a drug with no regulatory approval it may fall under S0 (non-approved substances) | Not named on the 2026 Prohibited List |
Amylin and GLP-1: Two Different Fullness Signals
Amylin is a hormone released by the pancreas with insulin; it slows stomach emptying, lowers glucagon after meals and promotes fullness. GLP-1 is a gut hormone that boosts insulin release and reduces appetite. Because the pathways differ, combining them was expected to add to each other, which is the rationale for CagriSema.
Cagrilintide
Primary Target: Amylin receptors and the calcitonin receptor
Affinity Profile: Nonselective amylin and calcitonin receptor agonist in cell studies; lipidated for weekly action
Engineered from amylin to avoid clumping into fibrils and to last long enough for weekly injection. In cell assays it activated both amylin and calcitonin receptors, unlike the older amylin analogue pramlintide.
Semaglutide
Primary Targets: GLP-1 receptor
Affinity Profile: Selective GLP-1 receptor agonist
Supports glucose-dependent insulin release, lowers glucagon and reduces food intake.
FDA Status: Semaglutide Approved, Cagrilintide and CagriSema Not
United States status checked 10–11 October 2026.
Cagrilintide Status & Formulations
Neither cagrilintide nor CagriSema is FDA-approved; no record appears in Drugs@FDA or DailyMed. FDA states cagrilintide is not a component of any FDA-approved drug, has not been found safe and effective for any condition and cannot be used in compounding.
Semaglutide Status & Formulations
Ozempic injection covers type 2 diabetes and specified cardiovascular and kidney risk indications. Rybelsus and Ozempic tablets have their own diabetes and cardiovascular indications. Wegovy injection and tablets cover defined weight and cardiovascular indications; pediatric and MASH indications differ by formulation.
Critical Regulatory Distinction
An approved semaglutide product does not make CagriSema or cagrilintide approved. Mixing semaglutide with online cagrilintide is not the trial combination and has no approved use.
Cagrilintide Alone, Semaglutide Alone and CagriSema
Figures from different trials are not directly comparable. The direct comparisons below come from trials that randomized participants to more than one of these treatments.
Cagrilintide: Alone and within CagriSema
Alone: a 26-week phase 2 trial (706 on cagrilintide, 99 on liraglutide, 101 on placebo; no diabetes) found weight loss of 6.0% to 10.8% vs 3.0% with placebo; the top dose group lost more than liraglutide (10.8% vs 9.0%). In a 32-week phase 2 trial in type 2 diabetes, cagrilintide alone lowered weight 8.1% and HbA1c 0.9 percentage points. Within CagriSema: REDEFINE 1 (3,417 adults without diabetes, 68 weeks) found −20.4% with CagriSema vs −3.0% with placebo; the trial also had cagrilintide-alone and semaglutide-alone arms, but the published abstract reports only the combination-versus-placebo result. REDEFINE 2 (1,206 adults with type 2 diabetes): −13.7% vs −3.4%.
Semaglutide: Alone and within CagriSema
Alone: STEP 1 found −14.9% vs −2.4% with placebo over 68 weeks; SELECT showed fewer major cardiovascular events than placebo (6.5% vs 8.0%). Against CagriSema: in REDEFINE 5 (331 adults in Japan and Taiwan, 68 weeks), CagriSema lowered weight 18.4% vs 11.9% with semaglutide alone. In REIMAGINE 2 (2,713 adults with type 2 diabetes), HbA1c fell 1.91 points with CagriSema vs 1.75 with semaglutide alone, a small but statistically significant difference. In the 32-week phase 2 trial, semaglutide alone lowered weight 5.1% and HbA1c 1.8 points.
Curated Clinical Evidence Table
A curated selection of the primary studies behind each compound’s evidence profile. Results from different studies are not directly comparable.
| Study & Citation | Population | Comparison & Dosing | Duration | Main Endpoint | Key Finding | Methodological Limitations |
|---|---|---|---|---|---|---|
| Phase 2 three-arm trial (Frias et al., Lancet 2023) | 92 adults with type 2 diabetes on metformin, with or without an SGLT2 inhibitor | CagriSema vs semaglutide alone vs cagrilintide alone, double-blind | 32 weeks | HbA1c change; body-weight change (secondary) | Weight: −15.6% CagriSema, −5.1% semaglutide, −8.1% cagrilintide. HbA1c: −2.2, −1.8 and −0.9 points. CagriSema beat both for weight; for HbA1c it beat cagrilintide but not semaglutide (p=0.075). | Small and short; no reported statistical test of cagrilintide vs semaglutide. Funded by Novo Nordisk. |
| Cagrilintide phase 2 (Lau et al., Lancet 2021) | Adults with overweight or obesity, without diabetes; 706 on cagrilintide | Cagrilintide (five dose levels) vs liraglutide vs placebo | 26 weeks | Percent change in body weight | −6.0% to −10.8% vs −3.0% with placebo; top dose vs liraglutide 10.8% vs 9.0%. | Short; not compared with semaglutide. Industry funded. |
| REDEFINE 1 (Garvey et al., NEJM 2025) | 3,417 adults with overweight or obesity, without diabetes | CagriSema vs semaglutide alone vs cagrilintide alone vs placebo (21:3:3:7) | 68 weeks | Percent change in body weight, CagriSema vs placebo | −20.4% vs −3.0% with placebo (difference −17.3 points). | Abstract does not report the single-drug arm results; primary comparison is against placebo. |
| REDEFINE 5 (Yamauchi et al., Lancet Diabetes Endocrinol 2026) | 331 adults in Japan and Taiwan with overweight or obesity, with or without type 2 diabetes | CagriSema vs semaglutide alone | 68 weeks | Percent change in body weight (trial product estimand) | −18.4% vs −11.9% (difference −6.5 points). | East Asian population; no cagrilintide-alone arm. |
| REIMAGINE 2 (Buse et al., Lancet Diabetes Endocrinol 2026) | 2,713 adults with type 2 diabetes on metformin, with or without an SGLT2 inhibitor | CagriSema vs semaglutide alone vs cagrilintide alone vs placebo | 68 weeks | HbA1c change, CagriSema vs semaglutide | −1.91 vs −1.75 points (difference −0.16). | Small added glucose benefit; abstract gives cagrilintide-alone safety but not efficacy figures. |
| STEP 1 (Wilding et al., NEJM 2021) | 1,961 adults with overweight or obesity, without diabetes | Weekly injectable semaglutide vs placebo | 68 weeks | Percent change in body weight | −14.9% vs −2.4% with placebo. | Separate trial; not directly comparable with REDEFINE 1 or the cagrilintide phase 2 trial. |
Adverse Effects Alone and in Combination
Gastrointestinal effects dominate for both drugs and are more frequent with the combination than with placebo. Cagrilintide has no FDA label.
Semaglutide only: Boxed Warning for thyroid C-cell tumors
Semaglutide labels carry a boxed warning because thyroid C-cell tumors occurred in rodents; whether this happens in humans is unknown. Cagrilintide and CagriSema have no FDA label, so no labelled warnings exist; that is not evidence they are safer.
| Safety Consideration | Cagrilintide | Semaglutide |
|---|---|---|
| Gastrointestinal adverse events vs placebo | Cagrilintide alone (phase 2): 41%–63% vs 32%, mainly nausea (20%–47% vs 18%) | Semaglutide alone (STEP 1): nausea and diarrhoea most common; 4.5% stopped for gastrointestinal events vs 0.8% |
| In combination (CagriSema) | REDEFINE 1: gastrointestinal events 79.6% vs 39.9% with placebo | REDEFINE 5: gastrointestinal events 53% with CagriSema vs 51% with semaglutide alone |
| Any adverse event (REIMAGINE 2) | Cagrilintide alone: 82.2%; CagriSema: 86.9% | Semaglutide alone: 81.2%; placebo: 70.5% |
| Label warnings | None (no FDA label) | Pancreatitis, gallbladder disease, dehydration-related kidney injury, hypoglycemia with insulin or an insulin secretagogue; see product label |
What Cagrilintide and Semaglutide Have in Common
Where the two compounds overlap in biology, evidence or regulatory context.
Weekly injections from the same developer
Both are long-acting peptides from Novo Nordisk, designed for weekly injection.
Appetite reduction
Both reduce food intake and slow stomach emptying, through different hormone pathways.
Gastrointestinal side effects
Nausea is the most common side effect for both.
Key Scientific & Clinical Differences
Meaningful distinctions in mechanism, strength of evidence, safety and regulatory status.
Different hormone systems
Cagrilintide mimics amylin; semaglutide mimics GLP-1.
Glucose effect
In the phase 2 diabetes trial, semaglutide lowered HbA1c more than cagrilintide alone (1.8 vs 0.9 points), while cagrilintide lowered weight more (8.1% vs 5.1%); no direct statistical test was reported.
Approval and outcomes
Semaglutide is approved with cardiovascular outcome data; cagrilintide has neither, and its CagriSema outcomes trial (REDEFINE 3) is ongoing.
Scientific Comparison vs Clinical Recommendations
Inside Peptides compares scientific evidence, receptor pharmacology, and official regulatory documents to advance public and professional understanding. We do not determine which compound is appropriate for an individual patient, rank medications with arbitrary scores, or recommend initiating or switching treatments.
Decisions about any medicine require a licensed healthcare professional who can weigh personal medical history, contraindications, interactions and monitoring needs. Unapproved peptides have no established safe use, and products sold as “research chemicals” are not the preparations studied in clinical research.
Approved Uses vs Online Claims
A critical scientific distinction between verified, FDA-approved clinical uses and unverified claims circulating on social media and vendor platforms.
Adding cagrilintide to semaglutide roughly doubles weight loss
Partly supportedCagriSema is not FDA-approved.
In trials that randomized both, CagriSema produced more weight loss than semaglutide alone (for example 18.4% vs 11.9% in REDEFINE 5). The size of the gain varies by trial and population, and the combination also brings more gastrointestinal effects than placebo.
Combining prescription semaglutide with online cagrilintide recreates CagriSema
Not supportedFDA states cagrilintide cannot be used in compounding.
Trial CagriSema is a manufactured product with controlled quality. Online cagrilintide is unapproved and unverified, and self-made combinations have not been studied.
Evidence Strength Across Clinical Domains
Inside Peptides evaluates scientific certainty at the claim level. Because clinical evidence varies significantly depending on the therapeutic endpoint evaluated, each domain is assessed independently.
Weight reduction, single drug
Cagrilintide alone has phase 2 efficacy data and phase 3 arms not yet fully reported in abstracts; semaglutide alone has multiple phase 3 trials and approval.
Weight reduction, as CagriSema
Phase 3 trials show the combination beats placebo and semaglutide alone; it is not approved and long-term outcomes are pending.
Cardiovascular outcomes
SELECT showed benefit for semaglutide; REDEFINE 3 (CagriSema) has not reported.
Cagrilintide vs semaglutide directly
One small 32-week phase 2 trial in type 2 diabetes gives both single-drug results, without a reported head-to-head test.
What Research Still Doesn’t Tell Us
Identifying open scientific questions, pending active-comparator trials, and areas where long-term clinical data remain incomplete.
Single-drug arms of large trials
REDEFINE 1 and REIMAGINE 2 randomized participants to cagrilintide alone and semaglutide alone; full comparison of those arms should be read in the full papers, not inferred from abstracts.
Cardiovascular outcomes
REDEFINE 3 is testing CagriSema in people with cardiovascular disease; it is active, not recruiting.
Cagrilintide on its own
A phase 3 program for cagrilintide alone (RENEW 1) is under way, so its standalone evidence is still early.
Industry funding
All trials summarized here were funded by Novo Nordisk.
Related Compound Profiles
Individual profiles provide full molecular datasheets, CAS numbers, preclinical histories, and compound monographs.
Related Educational Resources
Scientific & Regulatory References
Every pharmacological mechanism, clinical trial result, and regulatory approval cited on this page is traceable to official FDA prescribing documentation, ClinicalTrials.gov registries, or peer-reviewed medical publications.
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Phase 2 randomized controlled trial · Three-arm
Efficacy and safety of co-administered once-weekly cagrilintide 2·4 mg with once-weekly semaglutide 2·4 mg in type 2 diabetes: a multicentre, randomised, double-blind, active-controlled, phase 2 trialArticle title reproduced as published; it is not dosing guidance. Registry: phase 2, completed, 92 enrolled.
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Phase 2 randomized controlled trial
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
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Phase 3 randomized controlled trial
Coadministered Cagrilintide and Semaglutide in Adults with Overweight or Obesity
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Phase 3 randomized controlled trial
Cagrilintide-Semaglutide in Adults with Overweight or Obesity and Type 2 Diabetes
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Phase 3 randomized controlled trial · Active comparator
Efficacy and safety of co-administered cagrilintide and semaglutide versus semaglutide alone in adults with overweight or obesity with or without type 2 diabetes in Japan and Taiwan (REDEFINE 5): a multicentre, randomised, active-controlled, phase 3a trial
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Phase 3 randomized controlled trial · Active comparator
Cagrilintide-semaglutide (CagriSema) versus semaglutide or cagrilintide in people with type 2 diabetes (REIMAGINE 2): a double-blind, randomised, controlled, phase 3 study
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In vitro receptor pharmacology
AM833 Is a Novel Agonist of Calcitonin Family G Protein-Coupled Receptors: Pharmacological Comparison with Six Selective and Nonselective AgonistsAM833 is cagrilintide. Cell-based study; funded by Novo Nordisk.
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Medicinal chemistry
Development of Cagrilintide, a Long-Acting Amylin Analogue
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Phase 3 randomized controlled trial
Once-Weekly Semaglutide in Adults with Overweight or Obesity
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Cardiovascular outcomes trial
Semaglutide and Cardiovascular Outcomes in Obesity without Diabetes
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Registry record
REDEFINE 3: A Research Study to See the Effects of CagriSema in People Living With Diseases in the Heart and Blood Vessels
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Registry record
Weight Loss in People Living With Overweight or Obesity Following Treatment With Cagrilintide (RENEW 1)
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FDA safety communication
FDA's concerns with unapproved GLP-1 drugs used for weight loss
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Official U.S. prescribing information
Wegovy injection and tablets, current U.S. label
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Official U.S. prescribing information
Ozempic injection, current U.S. label