Cagrilintide Side Effects: 20 to 47% Nausea, 18% on Placebo

The phase 2 publication describes cagrilintide as "a long-acting amylin analogue under investigation for weight management" (PMID 34798060). Across its five dose groups, nausea was reported in 20 to 47 % versus 18 % on placebo during the 26-week treatment period plus 6-week follow-up (PMID 34798060). As of 2026-09-09 a DailyMed search for 'cagrilintide' returned 0 product labels and a search for 'cagrisema' returned 0 product labels; the control search 'tirzepatide' returned 4 labels (the Zepbound and Mounjaro records), so the query path works. No product label was read for this article.

The evidence base is the two posted registry tables, the abstracts of the phase 2 trials (Lau 2021, Frias 2023), REDEFINE 1, 2 and 5 and REIMAGINE 1, 2 and 3, the REDEFINE 1 blood-pressure analysis, the phase 1b, thorough-QT and organ-impairment studies, and three meta-analyses. Only registry tables and scientific publications supply results; personal accounts, vendor pages and press releases are outside this report. For the compound itself see our cagrilintide overview article.

Cagrilintide is listed at PeptidesDirect as a research-grade peptide. The study record is summarized on our cagrilintide study reference page. PeptidesDirect does not sell semaglutide and does not sell CagriSema. The dose arms named in this article are study arms of the cited trials, not an application protocol for research vials.

Cagrilintidemetabolic

Cagrilintide (AM833) is a long-acting synthetic analogue of the hormone amylin, acting at amylin receptors built from the calcitonin receptor and RAMP proteins. Supplied as a lyophilized powder for in-vitro research, with a batch-specific CoA.

Cagrilintide and the trial record

CagriSema is the name of the cagrilintide-semaglutide trial product in NCT04982575, REDEFINE and REIMAGINE. The primary endpoint of the phase 2 trial NCT03856047 was body weight change (PMID 34798060); efficacy results are not part of this report. The table lists what each record read for this article contributes.

REDEFINE 1 randomized 302 participants to cagrilintide alone versus 705 to placebo (PMID 40544433).

Gastrointestinal events: cagrilintide alone

Participants affected, week 0 to week 32 (NCT03856047 posted results). Terms below the registry frequency threshold for other events do not appear; absence of a row is not evidence of absence.

Across five dose groups, gastrointestinal events were 41 to 63 % versus 32 % on placebo, and nausea in 20 to 47 % versus 18 %, during the 26-week treatment period plus 6-week follow-up (PMID 34798060).

For baseline (week 0) to week 37, NCT04982575 posted results report:

The Frias 2023 abstract separately reports any adverse event in 24 of 30 on cagrilintide alone versus 22 of 31 on semaglutide alone over the 32-week trial (PMID 37364590). Denominators: randomized and dosed participants.

Injection-site reactions

Quoted MedDRA terms below count participants from week 0 to week 32 (NCT03856047 posted results). The terms overlap and are never summed.

• "Injection site reaction": 12 of 102 in the 2.4 mg arm; 10 of 101 in the 4.5 mg arm; placebo 0 of 101 (NCT03856047 posted results).
• "Injection site erythema": 7 of 102 in the 2.4 mg arm; 17 of 101 in the 4.5 mg arm; placebo 0 of 101 (NCT03856047 posted results).
• "Injection site pruritus": 7 of 102 in the 2.4 mg arm; 7 of 101 in the 4.5 mg arm; placebo 0 of 101 (NCT03856047 posted results).
• "Injection site rash": 0 of 102 in the 2.4 mg arm; 6 of 101 in the 4.5 mg arm; placebo 0 of 101 (NCT03856047 posted results).

NCT04982575 reported "Injection site reaction" in 2 of 30 on cagrilintide alone versus 0 of 31 on semaglutide alone, baseline (week 0) to week 37 (NCT04982575 posted results).

Pooled over three randomized controlled trials (RCTs), n = 3545, CagriSema versus semaglutide: administration-site risk ratio (RR) 3.27, 95 % confidence interval (CI) 1.27 to 8.46 (PMID 41834765). A pooled estimate is never broken down per trial.

Fatigue, dizziness and appetite

From week 0 to week 32, the cagrilintide 4.5 mg arm versus placebo pool recorded fatigue in 20 of 101 versus 3 of 101, dizziness in 9 of 101 versus 3 of 101, and decreased appetite in 17 of 101 versus 4 of 101 participants (NCT03856047 posted results).

Serious adverse events and deaths

From week 0 to week 32, serious events affected 3 of 102 in the cagrilintide 2.4 mg arm and 4 of 101 in the 4.5 mg arm, versus 3 of 101 on placebo (NCT03856047 posted results). Deaths: 0 of 101 (0.3 mg arm), 0 of 100 (0.6 mg arm), 0 of 102 (1.2 mg arm), 0 of 102 (2.4 mg arm) and 0 of 101 (4.5 mg arm), versus 0 of 101 on placebo, week 0 to week 32 (NCT03856047 posted results).

Serious cholelithiasis affected 1 of 101 in the 4.5 mg arm; serious biliary colic affected 1 of 102 in the 1.2 mg arm, each versus 0 of 101 on placebo, week 0 to week 32 (NCT03856047 posted results).

From baseline (week 0) to week 37, cagrilintide alone versus semaglutide alone had serious events in 4 of 30 versus 2 of 31; acute myocardial infarction and pulmonary embolism each affected 1 of 30 versus 0 of 31 (NCT04982575 posted results). Participants affected and serious terms are different counts, never added. The Frias 2023 abstract reports no fatal adverse events across arms over the 32-week trial (PMID 37364590).

REDEFINE 5 reported one death in the semaglutide 2.4 mg arm over the 68-week treatment period; no CagriSema death count is printed (PMID 42009015). REIMAGINE 3 reported one death in the CagriSema 1.0 mg-each arm over the 40-week treatment period; other groups have no printed death count (PMID 42251856).

Pooled cagrilintide monotherapy versus semaglutide: serious-event RR 1.83, 95 % CI 1.03 to 3.24, across 3 RCTs, n = 3545 (PMID 41834765). See the cagrilintide versus semaglutide meta-analysis article.

The network of 25 RCTs reported serious-event RRs versus placebo of 1.66 (95 % CI 0.43 to 6.35) for the cagrilintide 4.5 mg arm and 1.76 (95 % CI 1.06 to 2.91) for the cagrilintide 2.4 mg plus semaglutide 2.4 mg node; certainty was Moderate (PMID 42207966, PMC13239642). A pooled estimate is never broken down per trial.

CagriSema in the phase 3 abstracts

Over the 68-week treatment period, REDEFINE 1 reported gastrointestinal events in 79.6 % on CagriSema versus 39.9 % on placebo (PMID 40544433). REDEFINE 2, in adults with type 2 diabetes, reported 72.5 % versus 34.4 % over its 68-week treatment period (PMID 40544432).

REDEFINE 5 reported any adverse event in 143 of 164 on CagriSema versus 141 of 167 on semaglutide 2.4 mg, and gastrointestinal disorders in 87 of 164 versus 85 of 167, during the 68-week treatment period (PMID 42009015). Trial-product discontinuation was 17 (10 %) versus 10 (6 %), reason not specified in the abstract (same period, PMID 42009015).

REIMAGINE abstracts report any adverse event:

The abstracts are put in context in our REIMAGINE article.

In phase 1b NCT03600480, the cagrilintide 0.16 to 4.5 mg plus semaglutide 2.4 mg cohorts versus placebo plus semaglutide 2.4 mg had events in 69 of 71 versus 23 of 24 exposed participants, baseline to end of follow-up: 16 weeks of co-escalation, 4 weeks at target, then 5 weeks of follow-up (PMID 33894838). Gastrointestinal disorders accounted for 207 of 566 events (37 %) across groups in that window: events, not participants; no comparator share printed (PMID 33894838).

Pooled over three RCTs, n = 3545, CagriSema versus semaglutide: nausea RR 1.64 (95 % CI 1.01 to 2.66) (PMID 41834765). Another analysis pooled 4 RCTs, n = 4,419: trial product 3,055, control 1,364; gastrointestinal RR 1.32 versus semaglutide or placebo, no confidence interval printed in the abstract (PMID 41759565).

Blood pressure and hypotension in REDEFINE 1

REDEFINE 1 secondary analysis, systolic estimated change from baseline to week 68, using the trial-product estimand: CagriSema -10.9 mm Hg versus placebo -2.8 mm Hg, estimated treatment difference -8.2 mm Hg (95 % CI -9.3 to -7.1); cagrilintide alone -5.2 mm Hg versus placebo -2.8 mm Hg, difference -2.4 mm Hg (95 % CI -4.1 to -0.8) (PMID 41328546, PMC12822771).

Hypotension-related adverse events in REDEFINE 1 affected 38 (1.8 %) on CagriSema versus 3 (0.4 %) on placebo over the 68-week treatment period (PMID 41328546, PMC12822771).

Heart rhythm: QT and pulse

The thorough-QT study NCT05804162 exposed 105 healthy participants (PMID 39279639). Upper limits of the two-sided 90 % CIs of placebo-adjusted QTcF change were below 10 ms at 12, 24, 48 and 72 h after the last 4.5 mg dose (PMID 39279639).

None of the 18 records read for this article prints a heart-rate change in beats per minute. REDEFINE 1 measured pulse at 13 timepoints but prints no result (PMID 41328546, PMC12822771, Methods).

Hypoglycemia in the diabetes trials

The Frias 2023 abstract reports no level 2 or 3 hypoglycemia episodes across arms over the 32-week trial (PMID 37364590). REIMAGINE 3 reported no severe hypoglycemia across arms over the 40-week treatment period on background basal insulin (PMID 42251856).

Renal and hepatic impairment studies

NCT04209049 (renal 0.6 mg arm) and NCT05564104 (hepatic 0.9 mg arm) were uncontrolled, open-label, non-randomized single-dose studies (PMID 42228334, PMC13356073). In the renal study, day 1 to day 36, any event affected 8 of 14 with normal function versus 0 of 5 with severe impairment. "Injection site reaction" affected 4 of 14 with normal function versus 0 of 7, 0 of 7 and 0 of 5 with mild, moderate and severe impairment, respectively. No serious events, event-related withdrawals or deaths were reported across renal groups in that window (PMID 42228334, PMC13356073). Across both studies, the most frequent terms were nausea, vomiting, decreased appetite and "Injection site erythema" (PMID 42228334, PMC13356073).

Discontinuation and retention

The Lau 2021 abstract reports permanent discontinuation in 73 (10 %), discontinuation attributed to adverse events in 30 (4 %), and trial withdrawal in 29 (4 %), during the 26-week treatment period plus 6-week follow-up. All are pooled over all groups, not broken down per arm in the abstract (PMID 34798060).

Non-completion of the overall study was 7 of 101 in the cagrilintide 4.5 mg arm versus 6 of 101 on placebo (NCT03856047 posted results). The registry lists only "Withdrawal by Subject" and "Lost to Follow-up" as reasons and has no "Adverse Event" reason row. NCT04982575 recorded 0 of 30 on cagrilintide alone versus 2 of 31 on semaglutide alone over the overall study, only "Withdrawal by Subject", no "Adverse Event" reason row (NCT04982575 posted results).

REIMAGINE 2 retained 2376 of 2713 (87.6 %) on treatment at week 68, pooled across arms (PMID 42251859). For REDEFINE 5, the trial-product discontinuation figures given above carry no reason in the abstract (PMID 42009015).

Across 25 RCTs, discontinuation due to adverse events versus placebo had RR 0.23 (95 % CI 0.03 to 1.94) for the cagrilintide 4.5 mg arm and RR 2.22 (95 % CI 1.39 to 3.54) for the cagrilintide 2.4 mg plus semaglutide 2.4 mg node; the certainty ratings printed for treatment discontinuation are "overwhelmingly" Very Low (PMID 42207966, PMC13239642).

None of the six phase 3 abstracts prints adverse-event discontinuation per arm: REDEFINE 1, 2 and 5 (PMID 40544433, PMID 40544432, PMID 42009015), REIMAGINE 1, 2 and 3 (PMID 42251860, PMID 42251859, PMID 42251856).

Gaps in the identified records

As of 2026-09-09, no completed trial of cagrilintide or CagriSema has published or posted an alopecia or hair-loss adverse-event rate (PubMed search: '(cagrilintide[tiab] OR cagrisema[tiab]) AND (alopecia[tiab] OR hair loss[tiab])', 0 hits; ClinicalTrials.gov search: 'cagrilintide AND alopecia', 0 studies). Neither posted table contains that row; a term below the other-event threshold would not appear (NCT03856047 posted results; NCT04982575 posted results). For the class background see our hair-loss article.

Neither posted table contains pancreatitis; neither lists hypersensitivity or psychiatric/mood terms above the other-event threshold (NCT03856047 posted results; NCT04982575 posted results). The serious rows include the hepatobiliary events above and delirium (NCT03856047 posted results). None of the six phase 3 abstracts prints pancreatitis, gallbladder, hypersensitivity or psychiatric-term numbers (PMID 40544433, PMID 40544432, PMID 42009015, PMID 42251860, PMID 42251859, PMID 42251856).

As of 2026-09-09 REDEFINE 4 (CagriSema vs tirzepatide, NCT06131437, completed 2025-12-08) has neither a primary publication in PubMed nor posted registry results. PubMed search: '(cagrisema[tiab] OR cagrilintide[tiab]) AND tirzepatide[tiab]', 42 hits; ClinicalTrials.gov search: 'CagriSema tirzepatide', 3 hits.

Registry checks on 2026-09-09 found no posted results for NCT05567796, NCT05394519, NCT05813925, NCT06323174, NCT06065540, NCT06323161 and NCT03600480. Cagrilintide-alone event rates from REDEFINE 1 require the paywalled full text (PMID 40544433); per-term results from the REIMAGINE 2 cagrilintide arm likewise require the paywalled full text (PMID 42251859).

Who the trials enrolled

The monotherapy trial enrolled adults without diabetes, BMI at least 30 kg/m2 or at least 27 kg/m2 with hypertension or dyslipidemia (PMID 34798060).

NCT04982575 enrolled adults with type 2 diabetes, BMI at least 27 kg/m2, on metformin with or without an SGLT2 inhibitor (PMID 37364590).

REDEFINE 1 enrolled adults without diabetes, BMI at least 30 kg/m2 or at least 27 kg/m2 with an obesity-related complication (PMID 40544433). REDEFINE 2 enrolled adults with type 2 diabetes, BMI at least 27 kg/m2, HbA1c 7 to 10 percent (PMID 40544432). REDEFINE 5 enrolled adults in Japan and Taiwan, with or without type 2 diabetes, BMI at least 27 kg/m2 with at least two obesity-related complications or at least 35 kg/m2 with at least one (PMID 42009015).

REIMAGINE populations had type 2 diabetes: early-stage, inadequately controlled with diet and exercise in REIMAGINE 1; inadequately controlled on metformin with or without an SGLT2 inhibitor, BMI at least 25 kg/m2, HbA1c 7.0 to 10.5 percent in REIMAGINE 2; on basal insulin with or without metformin in REIMAGINE 3 (PMID 42251860, PMID 42251859, PMID 42251856).

Phase 1b NCT03600480 enrolled otherwise healthy adults aged 18 to 55 years, BMI 27.0 to 39.9 kg/m2, at a US center (PMID 33894838).

The QT study enrolled healthy participants (PMID 39279639).

The impairment studies grouped adults by renal or hepatic function, normal to severe (PMID 42228334, PMC13356073).

Why totals differ

Treatment-emergent counts record events during the source's observation window. They do not establish attribution. The Frias 2023 abstract's any-event count was 24 of 30 in the cagrilintide arm over the 32-week trial (PMID 37364590). The registry's other-events-above-threshold total was 18 of 30, baseline (week 0) to week 37 (NCT04982575 posted results). These are different quantities. Both registries specify "Frequency threshold (other events): 5" (NCT03856047 posted results; NCT04982575 posted results). A pooled estimate covers several trials and is never split into per-trial counts, as with the cagrilintide monotherapy serious-event risk ratio versus semaglutide over three RCTs, n = 3545 (PMID 41834765). Participants affected and event terms are different counts: from baseline (week 0) to week 37, the cagrilintide-alone arm had 4 of 30 participants with at least one serious event versus 2 of 31 on semaglutide alone; acute myocardial infarction and pulmonary embolism each affected 1 of 30 versus 0 of 31, and these term counts are not additive (NCT04982575 posted results). A share of events is not a participant rate: gastrointestinal disorders accounted for 207 of 566 events (37 %) across both groups from baseline to end of follow-up in phase 1b NCT03600480, with no comparator share printed (PMID 33894838).

Retatrutide, tirzepatide and semaglutide

Cagrilintide is an amylin analogue (PMID 34798060), semaglutide a glucagon-like peptide-1 analogue (PMID 33894838). The compound-specific data for the three comparators are in our retatrutide side-effects article, our tirzepatide side-effects article and our semaglutide science article.

The only direct monotherapy comparison in this article is NCT04982575 (cagrilintide 2.4 mg alone versus semaglutide 2.4 mg alone); the pooled estimates are a separate line of evidence. The phase 2 trial carried a liraglutide 3.0 mg arm whose adverse-event counts are not part of this report (NCT03856047 posted results). PeptidesDirect does not sell tirzepatide. See the tirzepatide study page.

Open questions and reporting gaps

Paywalled papers and registry thresholds leave term-level gaps. Per-arm pulse results and a product label remain missing from the identified records. None of the six phase 3 abstracts read prints discontinuation due to adverse events per arm (PMID 40544433, PMID 40544432, PMID 42009015, PMID 42251860, PMID 42251859, PMID 42251856). Cagrilintide-alone event rates for the REDEFINE 1 arm require the paywalled full text (PMID 40544433), as do per-term numbers for the REIMAGINE 2 cagrilintide arm (PMID 42251859). Of the registry records read, only NCT03856047 and NCT04982575 carry posted results.

Conclusions for Research

In the posted phase 2 table, gastrointestinal terms and injection-site terms are the two groups that separate the cagrilintide arms from the placebo pool, and every injection-site term stands at 0 of 101 in that pool (NCT03856047 posted results). Serious-event counts per arm are small in both posted registries, while the pooled estimates against semaglutide come from meta-analyses and are not per-trial counts (PMID 41834765, PMID 42207966, PMC13239642). Discontinuation attributed to adverse events is available only pooled over all groups in the phase 2 abstract and not per arm in any phase 3 abstract read (PMID 34798060). Reliable interpretation keeps the source, the denominator and the observation window of every result.

Cagrilintide is listed at PeptidesDirect as a research-grade peptide. PeptidesDirect does not sell semaglutide and does not sell CagriSema.

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Sources and further reading:

- Lau DCW et al. 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. Lancet, 2021. PubMed: https://pubmed.ncbi.nlm.nih.gov/34798060/

- Frias JP et al. 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 trial. Lancet, 2023. PubMed: https://pubmed.ncbi.nlm.nih.gov/37364590/

- Garvey WT et al. Coadministered Cagrilintide and Semaglutide in Adults with Overweight or Obesity. N Engl J Med, 2025. PubMed: https://pubmed.ncbi.nlm.nih.gov/40544433/

- Davies MJ et al. Cagrilintide-Semaglutide in Adults with Overweight or Obesity and Type 2 Diabetes. N Engl J Med, 2025. PubMed: https://pubmed.ncbi.nlm.nih.gov/40544432/

- Yamauchi T et al. 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. Lancet Diabetes Endocrinol, 2026. PubMed: https://pubmed.ncbi.nlm.nih.gov/42009015/

- Buse JB et al. Cagrilintide-semaglutide (CagriSema) versus semaglutide or cagrilintide in people with type 2 diabetes (REIMAGINE 2): a double-blind, randomised, controlled, phase 3 study. Lancet Diabetes Endocrinol, 2026. PubMed: https://pubmed.ncbi.nlm.nih.gov/42251859/

- Aroda VR et al. Efficacy and safety of once-weekly cagrilintide-semaglutide (CagriSema) in adults with type 2 diabetes inadequately controlled on diet and exercise (REIMAGINE 1): a randomised, double-blind, placebo-controlled, phase 3a study. Lancet Diabetes Endocrinol, 2026. PubMed: https://pubmed.ncbi.nlm.nih.gov/42251860/

- Rosenstock J et al. Cagrilintide-semaglutide (CagriSema) as an add-on to basal insulin in adults with type 2 diabetes (REIMAGINE 3): a randomised, double-blind, placebo-controlled, multicentre, phase 3 study. Lancet, 2026. PubMed: https://pubmed.ncbi.nlm.nih.gov/42251856/

- Enebo LB et al. Safety, tolerability, pharmacokinetics, and pharmacodynamics of concomitant administration of multiple doses of cagrilintide with semaglutide 2.4 mg for weight management: a randomised, controlled, phase 1b trial. Lancet, 2021. PubMed: https://pubmed.ncbi.nlm.nih.gov/33894838/

- Verma S et al. CagriSema Reduces Blood Pressure in Adults With Overweight or Obesity: REDEFINE 1. Hypertension, 2026. Open access: https://pmc.ncbi.nlm.nih.gov/articles/PMC12822771/. PubMed: https://pubmed.ncbi.nlm.nih.gov/41328546/

- Gabe MBN et al. Cagrilintide is not associated with clinically relevant QTc prolongation: A thorough QT study in healthy participants. Diabetes Obes Metab, 2024. PubMed: https://pubmed.ncbi.nlm.nih.gov/39279639/

- Nielsen MJF et al. Renal or Hepatic Impairment Does Not Affect Pharmacokinetics, Safety, or Tolerability of Subcutaneous Cagrilintide. Clin Pharmacokinet, 2026. Open access: https://pmc.ncbi.nlm.nih.gov/articles/PMC13356073/. PubMed: https://pubmed.ncbi.nlm.nih.gov/42228334/

- Ahmed M et al. Efficacy and Safety of Cagrilintide and Cagrisema Versus Semaglutide as Anti-Obesity Medications: A Systematic Review, Meta-Analysis and Meta-Regression. Diabetes Obes Metab, 2026. PubMed: https://pubmed.ncbi.nlm.nih.gov/41834765/

- Gadelmawla AF et al. CagriSema Versus Semaglutide Monotherapy or Placebo for Obesity: A Systematic Review and Meta-Analysis of Randomized Controlled Trials with GRADE Assessment. Am J Cardiol, 2026. PubMed: https://pubmed.ncbi.nlm.nih.gov/41759565/

- Hamarsheh S et al. Comparative Effectiveness of CagriSegma, Semaglutide, Cagrilintide and Tirzepatide in the Management of Overweight and Obesity: A Network Meta-Analysis of Randomized Clinical Trials. Endocrinol Diabetes Metab, 2026. Open access: https://pmc.ncbi.nlm.nih.gov/articles/PMC13239642/. PubMed: https://pubmed.ncbi.nlm.nih.gov/42207966/

- ClinicalTrials.gov posted results: https://clinicaltrials.gov/study/NCT03856047, https://clinicaltrials.gov/study/NCT04982575

- ClinicalTrials.gov, no posted results: REDEFINE 1 https://clinicaltrials.gov/study/NCT05567796, REDEFINE 2 https://clinicaltrials.gov/study/NCT05394519, REDEFINE 4 https://clinicaltrials.gov/study/NCT06131437, REDEFINE 5 https://clinicaltrials.gov/study/NCT05813925, REIMAGINE 1 https://clinicaltrials.gov/study/NCT06323174, REIMAGINE 2 https://clinicaltrials.gov/study/NCT06065540, REIMAGINE 3 https://clinicaltrials.gov/study/NCT06323161

- ClinicalTrials.gov: phase 1b https://clinicaltrials.gov/study/NCT03600480, thorough-QT study https://clinicaltrials.gov/study/NCT05804162, renal impairment study https://clinicaltrials.gov/study/NCT04209049, hepatic impairment study https://clinicaltrials.gov/study/NCT05564104

This article is for informational purposes only for scientific research.

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Cagrilintidemetabolic

Cagrilintide (AM833) is a long-acting synthetic analogue of the hormone amylin, acting at amylin receptors built from the calcitonin receptor and RAMP proteins. Supplied as a lyophilized powder for in-vitro research, with a batch-specific CoA.