Evidence-Based Summary
No trial has compared cagrilintide alone with tirzepatide. Cagrilintide on its own has one placebo-controlled trial: over 26 weeks in adults with overweight or obesity, cagrilintide groups lost 6.0% to 10.8% of body weight versus 3.0% with placebo. Tirzepatide is an approved medicine with large phase 3 programs: in SURMOUNT-1 (2,539 adults without diabetes, 72 weeks), tirzepatide groups lost 15.0% to 20.9% versus 3.1% with placebo, and in SURMOUNT-5 it produced more weight loss than semaglutide in a direct trial. These are separate trials of different length and design, so the numbers do not rank the drugs. The only registered head-to-head involving cagrilintide is REDEFINE 4, which compares tirzepatide with CagriSema (cagrilintide plus semaglutide), not with cagrilintide alone; the trial is listed as completed, and its results have not been published in a peer-reviewed journal.
Quick Comparison: Cagrilintide vs Tirzepatide
A high-level comparison of molecule class, molecular receptor targets, FDA regulatory approvals, and verified clinical programs.
| Feature | Cagrilintide | Tirzepatide |
|---|---|---|
| Drug class | Investigational long-acting (lipidated) amylin analogue | Approved dual incretin receptor agonist (acylated peptide) |
| Target receptors | Amylin receptors and the calcitonin receptor (nonselective, in cell studies) | GIP and GLP-1 receptors |
| How it is given | Once-weekly injection under the skin, alone or with semaglutide (CagriSema), in clinical trials only | Once-weekly injection under the skin (Mounjaro, Zepbound) |
| U.S. regulatory status | Not FDA-approved, alone or as CagriSema; FDA states it cannot be used in compounding | FDA-approved for type 2 diabetes (Mounjaro) and for defined weight-management and sleep-apnea uses (Zepbound) |
| Direct comparison | None for cagrilintide alone. REDEFINE 4 compares CagriSema (with semaglutide) against tirzepatide; no peer-reviewed results | Same trial; tirzepatide is the comparator arm |
| Strongest outcomes evidence | Phase 2 placebo- and liraglutide-controlled trial alone; phase 3 trials mainly as part of CagriSema; no outcome trial reported | Multiple phase 3 trials, direct comparisons with semaglutide, and a cardiovascular outcomes trial against dulaglutide |
| Main safety concerns | Gastrointestinal effects, mainly nausea; injection-site reactions; no FDA label and no long-term data | Gastrointestinal effects; label warnings including pancreatitis and gallbladder disease; boxed warning based on rodent thyroid C-cell tumors |
| WADA status (2026) | Not named on the Prohibited List | Not named on the Prohibited List |
Amylin Receptors vs Incretin Receptors
Amylin is a pancreatic hormone released with insulin; it slows stomach emptying, limits the after-meal rise in glucagon and promotes fullness. GIP and GLP-1 are gut hormones (incretins) that increase insulin release when glucose is high and reduce appetite. The two drugs act on different receptor families, which is why cagrilintide is being developed alongside an incretin drug (semaglutide) rather than as a replacement for one.
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. It has no incretin-receptor activity.
Tirzepatide
Primary Targets: GIP and GLP-1 receptors
Affinity Profile: Dual agonist
Activates both incretin receptors, increasing glucose-dependent insulin release and reducing food intake. Human trials measure the whole medicine; they do not isolate how much of the effect comes from each receptor.
FDA Status: Tirzepatide Approved, Cagrilintide Not
Checked 18 October 2026 against Drugs@FDA and DailyMed. An approval belongs to a named product, formulation and population.
Cagrilintide Status & Formulations
Not FDA-approved, alone or combined with semaglutide as CagriSema. No cagrilintide product appears in Drugs@FDA or DailyMed. FDA states that 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.
Tirzepatide Status & Formulations
Mounjaro is approved for glycemic control in adults and children aged 10 years and older with type 2 diabetes. Zepbound is approved for defined adult weight-management indications and for moderate-to-severe obstructive sleep apnea in adults with obesity. Each label has its own eligibility criteria and limitations.
Critical Regulatory Distinction
Investigational status means cagrilintide is still in regulated clinical development. Products sold online as cagrilintide are unapproved and unverified. Compounded tirzepatide is not an FDA-approved equivalent of Mounjaro or Zepbound.
Cagrilintide and CagriSema Trials vs SURMOUNT and SURPASS
Cagrilintide's standalone evidence is a 26-week phase 2 trial; its 68-week phase 3 trials test it combined with semaglutide. Tirzepatide has placebo-controlled and active-comparator phase 3 trials and an outcomes trial. Results from different trials cannot be ranked against each other.
Cagrilintide: Clinical Evidence Overview
Alone: a 26-week phase 2 trial randomized 706 adults with overweight or obesity (no diabetes) to five cagrilintide dose levels, 99 to liraglutide and 101 to placebo; weight fell 6.0% to 10.8% across cagrilintide groups versus 3.0% with placebo, and the highest-dose group lost more than the liraglutide group (10.8% vs 9.0%). In a 32-week phase 2 trial in 92 adults with type 2 diabetes, cagrilintide alone lowered weight 8.1% and HbA1c 0.9 percentage points. As CagriSema: REDEFINE 1 (3,417 adults without diabetes, 68 weeks) reported −20.4% versus −3.0% with placebo; the cagrilintide-alone arm is not reported in the abstract. REIMAGINE 2 (2,713 adults with type 2 diabetes) found HbA1c fell 1.91 points with CagriSema versus 1.75 with semaglutide alone. A phase 3 program for cagrilintide alone (RENEW 1) is under way. All funded by Novo Nordisk.
Tirzepatide: Clinical Evidence Overview
SURMOUNT-1 randomized 2,539 adults with obesity or overweight without diabetes for 72 weeks: weight change was −15.0%, −19.5% and −20.9% across tirzepatide groups versus −3.1% with placebo. SURPASS-2 (1,879 adults with type 2 diabetes on metformin, 40 weeks) found HbA1c fell 2.01 to 2.30 percentage points across tirzepatide groups versus 1.86 with injectable semaglutide. SURMOUNT-5 (751 adults without diabetes, 72 weeks) found −20.2% with tirzepatide versus −13.7% with semaglutide. SURPASS-CVOT (13,299 adults with type 2 diabetes and cardiovascular disease) showed tirzepatide was noninferior, but not superior, to dulaglutide for major cardiovascular events (12.2% vs 13.1%; HR 0.92). All funded by Eli Lilly.
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 |
|---|---|---|---|---|---|---|
| Cagrilintide phase 2 (Lau et al., Lancet 2021) | Adults with overweight or obesity, without diabetes; 706 on cagrilintide, 99 on liraglutide, 101 on placebo | 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; highest dose group 10.8% vs liraglutide 9.0%. | Short; the only placebo-controlled trial of cagrilintide alone; not compared with tirzepatide. |
| Cagrilintide, semaglutide and CagriSema phase 2 (Frias et al., Lancet 2023) | 92 adults with type 2 diabetes on metformin, with or without an SGLT2 inhibitor | Cagrilintide alone vs semaglutide alone vs CagriSema, double-blind | 32 weeks | HbA1c change; body-weight change (secondary) | Cagrilintide alone: weight −8.1%, HbA1c −0.9 points. CagriSema: −15.6% and −2.2 points. | Small and short; no tirzepatide arm. |
| 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 | 68 weeks | Percent change in body weight, CagriSema vs placebo | −20.4% with CagriSema vs −3.0% with placebo (difference −17.3 points). | A combination result, not a cagrilintide-alone result; abstract does not report the single-drug arms. |
| SURMOUNT-1 (Jastreboff et al., NEJM 2022) | 2,539 adults with obesity or overweight, without diabetes | Tirzepatide (three dose groups) vs placebo | 72 weeks | Percent change in body weight | −15.0% to −20.9% with tirzepatide vs −3.1% with placebo. | Different trial, duration and population from the cagrilintide phase 2 trial; not directly comparable. |
| SURPASS-2 (Frías et al., NEJM 2021) | 1,879 adults with type 2 diabetes on metformin | Tirzepatide (three dose groups) vs injectable semaglutide | 40 weeks | HbA1c change | −2.01, −2.24 and −2.30 points vs −1.86 with semaglutide. | Open-label; a specific semaglutide regimen; no cagrilintide arm. |
| SURMOUNT-5 (Aronne et al., NEJM 2025) | 751 adults with obesity, without diabetes | Tirzepatide vs semaglutide, maximum tolerated regimens | 72 weeks | Percent change in body weight | −20.2% vs −13.7% (P<0.001). | Open-label; compares tirzepatide with semaglutide alone, not with CagriSema or cagrilintide. |
| SURPASS-CVOT (Nicholls et al., NEJM 2025) | 13,299 adults with type 2 diabetes and atherosclerotic cardiovascular disease | Tirzepatide vs dulaglutide | Event-driven | Cardiovascular death, heart attack or stroke | 12.2% vs 13.1%; HR 0.92 (95.3% CI 0.83–1.01); noninferior, not superior. | Active comparator, not placebo; no equivalent cagrilintide result exists. |
| REDEFINE 4 (NCT06131437, registry record) | 809 adults with obesity (actual enrollment) | CagriSema (cagrilintide plus semaglutide) vs tirzepatide, open-label | Not yet reported | Non-inferiority of CagriSema vs tirzepatide: relative change in body weight (registry) | Phase 3; listed as completed; no results posted on the registry and no peer-reviewed publication as of 18 October 2026. | Tests the combination with semaglutide, not cagrilintide alone; open-label; sponsor Novo Nordisk. |
Adverse Effects: Trial-Only Data vs an FDA Label
Tirzepatide's safety profile is described in FDA labels built on large trials and post-marketing experience. Cagrilintide's comes only from clinical trials, and its largest trials measured the CagriSema combination rather than cagrilintide alone.
Tirzepatide only: Boxed Warning for thyroid C-cell tumors
Tirzepatide labels carry a boxed warning because thyroid C-cell tumors occurred in rodents; whether this happens in humans is unknown, and tirzepatide is contraindicated with a personal or family history of medullary thyroid carcinoma or MEN 2. Cagrilintide has no FDA label, so no labelled warnings exist for it; that is not evidence that it is safer.
| Safety Consideration | Cagrilintide | Tirzepatide |
|---|---|---|
| Most common adverse effects | Gastrointestinal, mainly nausea; constipation, diarrhoea and administration-site reactions also reported | Gastrointestinal: nausea, diarrhoea, vomiting, mostly during dose escalation |
| Gastrointestinal adverse events vs placebo | Phase 2 alone: 41%–63% vs 32% with placebo; nausea 20%–47% vs 18%. As CagriSema (REDEFINE 1): 79.6% vs 39.9% | Frequencies depend on trial and regimen; see product label |
| Stopping because of adverse events | Not reported in the abstracts reviewed here for cagrilintide alone | SURMOUNT-1: 4.3% to 7.1% across tirzepatide groups vs 2.6% with placebo |
| Label warnings | None (no FDA label) | Pancreatitis, gallbladder disease, dehydration-related kidney injury, hypoglycemia with insulin or an insulin secretagogue, serious hypersensitivity, diabetic retinopathy complications; see product label |
| Long-term outcomes | Unknown; REDEFINE 3 tests CagriSema, not cagrilintide alone | Cardiovascular outcomes trial completed versus an active comparator |
Specific Drug Interaction Note
Tirzepatide labels advise a non-oral contraceptive method or an added barrier method for four weeks after starting and after each dose increase, because slowed stomach emptying can reduce oral contraceptive absorption. Whether cagrilintide has a similar interaction has not been established in a label.
What Cagrilintide and Tirzepatide Have in Common
Where the two compounds overlap in biology, evidence or regulatory context.
Once-weekly injection
Both are long-acting peptides given as once-weekly injections under the skin.
Appetite and weight
Both reduce food intake, slow stomach emptying and lowered body weight more than placebo in randomized trials.
Gastrointestinal side effects
Nausea and other gastrointestinal effects are the most common adverse events for both.
Key Scientific & Clinical Differences
Meaningful distinctions in mechanism, strength of evidence, safety and regulatory status.
Different hormone systems
Cagrilintide mimics amylin and acts on amylin and calcitonin receptors; tirzepatide acts on the GIP and GLP-1 incretin receptors.
Approval and experience
Tirzepatide is FDA-approved with years of prescribing data; cagrilintide is investigational, alone and as CagriSema.
Depth of evidence
Tirzepatide has multiple phase 3 trials, direct comparisons with semaglutide and an outcomes trial; cagrilintide alone has one 26-week phase 2 trial, with phase 3 data mainly for the combination.
Scientific Comparison vs Clinical Recommendations
InsidePeptides 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.
CagriSema matches or beats tirzepatide for weight loss
Not establishedCagriSema and cagrilintide are not FDA-approved; tirzepatide is approved as Mounjaro and Zepbound.
REDEFINE 4 was designed to test this question, with non-inferiority of CagriSema to tirzepatide on body weight as its primary endpoint. The registry lists the trial as completed, but no results have been posted or published in a peer-reviewed journal, so the claim cannot be assessed. Even when published, the result will describe the combination with semaglutide, not cagrilintide alone.
Adding online cagrilintide to tirzepatide gives a 'CagriSema-style' boost
Not supportedFDA states cagrilintide cannot be used in compounding and is not a component of any approved drug.
CagriSema pairs cagrilintide with semaglutide, not tirzepatide, and no published trial has tested cagrilintide with tirzepatide in people. Online cagrilintide is unapproved and unverified.
Evidence Strength Across Clinical Domains
InsidePeptides 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 in adults with obesity
Cagrilintide alone has one 26-week phase 2 trial; tirzepatide has multiple phase 3 trials and an approved weight-management label.
Glucose control in type 2 diabetes
Cagrilintide alone lowered HbA1c modestly in one small phase 2 trial; tirzepatide is approved for type 2 diabetes on a large phase 3 program.
Cardiovascular outcomes
No cagrilintide outcome data; tirzepatide was noninferior, not superior, to dulaglutide in SURPASS-CVOT.
Cagrilintide vs tirzepatide directly
No trial compares cagrilintide alone with tirzepatide; REDEFINE 4 compares the CagriSema combination and has no peer-reviewed results.
What Research Still Doesn’t Tell Us
Identifying open scientific questions, pending active-comparator trials, and areas where long-term clinical data remain incomplete.
REDEFINE 4 results
The CagriSema-versus-tirzepatide trial is listed as completed; until it is published in a peer-reviewed journal, no comparison can be drawn from it.
Cagrilintide on its own
Cagrilintide's standalone evidence is a 26-week phase 2 trial; the RENEW 1 phase 3 program will show whether its effect holds over longer periods.
Cagrilintide with tirzepatide
No published human trial has combined an amylin analogue with tirzepatide.
Industry funding
Cagrilintide trials were funded by Novo Nordisk and tirzepatide trials by Eli Lilly; no independent comparison exists.
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
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 trialThe only placebo-controlled trial of cagrilintide alone; funded by Novo Nordisk.
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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. 92 participants; funded by Novo Nordisk.
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Phase 3 randomized controlled trial · Combination
Coadministered Cagrilintide and Semaglutide in Adults with Overweight or ObesityREDEFINE 1; tests the CagriSema combination, not cagrilintide alone. Funded by Novo Nordisk.
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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 studyFunded by Novo Nordisk.
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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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Phase 3 randomized controlled trial
Tirzepatide Once Weekly for the Treatment of ObesitySURMOUNT-1; double-blind, 72 weeks, 2,539 adults without diabetes; funded by Eli Lilly.
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Phase 3 randomized controlled trial · Active comparator
Tirzepatide versus Semaglutide Once Weekly in Patients with Type 2 DiabetesSURPASS-2; open-label, 40 weeks, 1,879 adults on metformin; funded by Eli Lilly.
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Phase 3 randomized controlled trial · Head-to-head
Tirzepatide as Compared with Semaglutide for the Treatment of ObesitySURMOUNT-5; open-label, 72 weeks, 751 adults without diabetes; funded by Eli Lilly.
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Cardiovascular outcomes trial
Cardiovascular Outcomes with Tirzepatide versus Dulaglutide in Type 2 DiabetesActive-comparator noninferiority trial; funded by Eli Lilly.
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Registry record · Head-to-head (combination)
A Research Study to See How Well CagriSema Compared to Tirzepatide Helps People With Obesity Lose Weight (REDEFINE 4)REDEFINE 4 (NCT06131437). Official registry title reproduced as registered; it is not dosing guidance. Phase 3, open-label, 809 enrolled, listed as completed; no results posted; sponsor Novo Nordisk. Checked 18 October 2026.
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Registry record
Weight Loss in People Living With Overweight or Obesity Following Treatment With Cagrilintide (RENEW 1)Phase 3 program for cagrilintide alone; active, not recruiting; sponsor Novo Nordisk.
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FDA safety communication
FDA's concerns with unapproved GLP-1 drugs used for weight lossIncludes FDA's statement on cagrilintide.
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Official U.S. prescribing information
Zepbound, current labelChecked 18 October 2026.
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Official U.S. prescribing information
Mounjaro, current labelChecked 18 October 2026.