Six selected reports include cagrilintide alone and the cagrilintide-semaglutide combination known as CagriSema. The later combination trials address different populations and questions from the earlier cagrilintide-alone study.123456
Bottom line from this bounded source set
The selected cagrilintide-alone study reported weight reduction. Later combination trials reported weight or glycemic improvements, but their results cannot be attributed to cagrilintide alone. Gastrointestinal adverse events were common, and a correction to REIMAGINE 2 remains to be reconciled.123456
Reviewed study record
Phase 2 weight-management trial
Design
A multicenter, randomized, double-blind, placebo-controlled and active-controlled dose-finding trial assessed body-weight change over 26 weeks.1
Population
The trial randomized 906 adults without diabetes across 57 sites in ten countries: 706 to cagrilintide groups, 99 to liraglutide, and 101 to placebo. Participants had obesity, or overweight with hypertension or dyslipidemia.1
Outcomes reported
Reported mean body-weight reduction ranged from 6.0% to 10.8% across cagrilintide groups and was 3.0% with placebo. Gastrointestinal events occurred more often across cagrilintide groups than with placebo.1
Limitations
This was a sponsor-funded, 26-week Phase 2 dose-finding study in adults without diabetes, with a short off-treatment follow-up and no long-term clinical-outcomes assessment.1
Reviewed study record
REDEFINE 1: combination treatment without diabetes
Design
A blinded randomized phase 3a trial compared combination treatment, either component alone and placebo over 68 weeks under NCT05567796.2
Population
The trial randomized 3,417 adults with overweight or obesity without diabetes across four groups.2
Outcomes reported
The treatment-policy analysis reported mean weight changes of −20.4% with cagrilintide-semaglutide versus −3.0% with placebo. Gastrointestinal adverse events occurred in 79.6% and 39.9%, respectively.2
Limitations
These estimates concern the combination and cannot be attributed to cagrilintide alone. The abstract does not give the component-alone outcome estimates needed to assess each component’s contribution.2
Reviewed study record
REDEFINE 2: combination treatment with diabetes
Design
A blinded randomized placebo-controlled phase 3a trial assessed weight endpoints at 68 weeks under NCT05394519.3
Population
The study randomized 1,206 adults with type 2 diabetes and overweight or obesity.3
Outcomes reported
The treatment-policy analysis reported mean weight changes of −13.7% with cagrilintide-semaglutide versus −3.4% with placebo. Gastrointestinal adverse events occurred in 72.5% and 34.4%, respectively.3
Limitations
This comparison evaluates the combination against placebo, not either component alone. Weight and glycemic outcomes do not establish prevention of long-term complications.3
Reviewed study record
REIMAGINE 1: early type 2 diabetes
Design
A blinded randomized placebo-controlled phase 3a trial assessed 40-week HbA1c change under NCT06323174.4
Population
The trial randomized 189 adults whose type 2 diabetes was inadequately controlled with diet and exercise.4
Outcomes reported
Under the efficacy analysis, HbA1c fell by 1.8 and 1.5 percentage points in the combination groups versus 0.1 with placebo. Adverse events occurred in 79%, 75% and 66%, respectively, and were predominantly mild or moderate gastrointestinal events.4
Limitations
The efficacy estimand differs from the treatment-policy analyses in the REDEFINE reports. These populations, endpoints and analyses should not be combined into a simple treatment ranking.4
Reviewed study record
REIMAGINE 2: comparison with component treatments
Design
A blinded randomized trial compared cagrilintide-semaglutide with component treatments and placebo over 68 weeks under NCT06065540.5
Population
The report concerns adults with type 2 diabetes receiving metformin with or without an SGLT2 inhibitor.5
Outcomes reported
The primary comparison concerns HbA1c change with the combination versus semaglutide. A publisher erratum is linked to this report; its impact on the numerical comparison has not been reconciled here.5
Limitations
The exact treatment difference is withheld pending review of the linked correction. This source should not be used here to infer the size of an additional benefit or to rank treatments.5
A blinded randomized placebo-controlled phase 3a trial assessed 40-week HbA1c change under NCT06323161.6
Population
The study randomized 274 adults with type 2 diabetes receiving basal insulin, with or without metformin.6
Outcomes reported
Under the efficacy analysis, HbA1c fell by 2.33 and 2.10 percentage points in the combination groups versus 0.66 with placebo. Gastrointestinal events were common; no severe hypoglycemia was reported.6
Limitations
The report recorded one death due to malignancy in an active group, considered unrelated to treatment. Absence of severe hypoglycemia in this study does not establish absence of risk, and the findings are not an individualized treatment recommendation.6
No registered Crossref update in the reviewed snapshotChecked August 19, 2026 for DOI 10.1016/s0140-6736(21)01751-7. This bounded result is not proof that the publication has never been corrected or retracted. Open the pinned Crossref work endpoint ↗
No registered Crossref update in the reviewed snapshotChecked September 15, 2026 for DOI 10.1056/nejmoa2502081. This bounded result is not proof that the publication has never been corrected or retracted. Open the pinned Crossref work endpoint ↗
No registered Crossref update in the reviewed snapshotChecked September 15, 2026 for DOI 10.1056/nejmoa2502082. This bounded result is not proof that the publication has never been corrected or retracted. Open the pinned Crossref work endpoint ↗
No registered Crossref update in the reviewed snapshotChecked September 15, 2026 for DOI 10.1016/s2213-8587(26)00126-9. This bounded result is not proof that the publication has never been corrected or retracted. Open the pinned Crossref work endpoint ↗
Publication update registered by CrossrefErratum ↗ · publisher metadata · June 19, 2026 and August 1, 2026. Crossref metadata identifies the notice but does not by itself explain what wording changed.
No registered Crossref update in the reviewed snapshotChecked September 15, 2026 for DOI 10.1016/s0140-6736(26)01022-6. This bounded result is not proof that the publication has never been corrected or retracted. Open the pinned Crossref work endpoint ↗