Gathering the record
Relay is organizing the evidence and source boundaries.
Fixed-dose amylin analogue / GLP-1 receptor agonist combination
CagriSema is an investigational once-weekly combination of cagrilintide and semaglutide. Large Phase 3 trials found substantial average weight reduction, and several diabetes trials found improved blood-sugar control. A U.S. application is under review, but CagriSema is not FDA approved.
60-Second Overview
Start with what it is, why it matters, what research has shown, and what remains unknown. The science follows after the orientation.
Start here. These four answers explain why the compound matters before the page introduces the deeper science.
CagriSema is an investigational fixed combination of cagrilintide, which acts like the fullness hormone amylin, and semaglutide, which acts through a gut-hormone pathway called GLP-1.
Researchers are testing whether combining two distinct appetite-related signals changes weight and blood-sugar outcomes compared with either component alone. Separate programs study people with and without type 2 diabetes.
Large peer-reviewed Phase 3 trials have reported substantial average weight reduction, and several diabetes trials have reported improved blood-sugar measures. Gastrointestinal effects were common, and each result belongs to the exact combination, population, and study design used.
CagriSema is not FDA approved. The regulatory decision, final product instructions, long-term cardiovascular and kidney outcomes, rare harms, durability after treatment ends, and broader comparisons remain unresolved.
The research depth, routes, studies, and primary sources below explain how Relay knows—and where the evidence stops.
Research context
Published research has investigated this compound using the following study designs.
These records explain what researchers did. They are not instructions, recommendations, or a transferable protocol.
A published Phase 3 trial evaluated the fixed combination in adults without diabetes who had obesity or overweight plus a related complication.
Reported study administration—not a recommendation.
Research at a glance
Evidence depth, confidence, and route context explain how Relay knows—not what anyone should do.
Multiple peer-reviewed Phase 3 trials cover weight and glycaemic outcomes across several defined populations.
Research depth describes how large and mature the overall record is. It does not tell you whether the results were positive.
Large randomized trials are consistent, while regulatory review, long-term outcomes, rare events, and durability remain unresolved.
Confidence describes how reliable and consistent the conclusions are. It can be high for one outcome and low for another.
The strongest evidence type shows what the best-supported conclusions are actually based on.
Human findings are more directly relevant than animal or laboratory results, but they still apply only to the populations and outcomes studied.
Route-specific record
These are exposures used in cited research for a specific route and population—not an instruction for an individual.
Half-life describes how long it takes the measured amount in the body to fall by half. It is not a dosing recommendation.
Evidence can change by administration method. Findings from one route should not automatically be applied to another.
Evidence boundary: The study compared several arms and used lifestyle intervention; its averages do not predict an individual result. The trial does not establish an approved product, long-term outcomes, or reconstitution and stability rules for independent material. Amounts shown describe cited research exposure—not a dosage recommendation.
Detailed evidence
Start with the strongest supported conclusion and its main uncertainty. Claim-level records below show how the evidence changes by question, population, route, formulation, and study design.
Two pivotal peer-reviewed weight-management trials randomized 3,417 adults without diabetes and 1,206 adults with type 2 diabetes, supported by three additional peer-reviewed Phase 3 diabetes trials.
This is the strongest supported conclusion in the current human evidence—not a summary of every claim made about the compound.
The FDA decision and final label, long-term cardiovascular and renal outcomes, rare adverse events, durability after discontinuation, and how outcomes compare across broader populations.
Keeping the main uncertainty visible prevents an early or promising finding from looking more settled than it is.
Questions people bring to the evidence
Research questions—not promises of benefit.
It combines amylin-related signaling from cagrilintide with GLP-1 receptor agonism from semaglutide. The combination has its own evidence record and is not interchangeable with either component alone.
REDEFINE 1 reported -20.4% versus -3.0% placebo without diabetes, while REDEFINE 2 reported -13.7% versus -3.4% placebo with type 2 diabetes under treatment-policy estimands.
REDEFINE 2, REIMAGINE 1, REIMAGINE 2, and REIMAGINE 3 studied different diabetes populations, including diet-only, oral-medication, obesity, and basal-insulin settings.
At the 2.4 mg/2.4 mg trial level, CagriSema produced a larger HbA1c reduction than semaglutide 2.4 mg and larger average weight reduction than the active comparator arms.
Nausea, vomiting, diarrhea, constipation, abdominal pain, and other gastrointestinal disorders were commonly reported and were usually described as transient and mild to moderate.
At week 68, systolic and diastolic blood pressure fell more in the CagriSema group than in the placebo group.
The sponsor reported submitting a U.S. new drug application for weight management. No FDA approval or approved CagriSema label was identified through July 25, 2026.
Those trial details explain how the studies were conducted. They are not an approved consumer dose, schedule, or individualized recommendation.
The studies used sponsor-controlled investigational injections. That does not create a public standard for handling unapproved products or separately sourced components.
CagriSema already contains both compounds. Adding another GLP-1 receptor agonist would also add direct pathway overlap.
Mechanisms
CagriSema combines the long-acting amylin analogue cagrilintide with the GLP-1 receptor agonist semaglutide. REDEFINE 1 and 2 studied weight management in adults without and with type 2 diabetes; REIMAGINE 1, 2, and 3 studied glycemic control across diet-only, oral-medication, and basal-insulin populations. REIMAGINE 2 directly compared the combination with semaglutide and cagrilintide. These combination outcomes must remain separate from monotherapy evidence.
A plausible mechanism can explain why a study was attempted. It does not prove that the compound improves a human outcome.
Studies
Study arms are reported for transparency. They describe what researchers did in a defined record and do not transfer across identities, routes, formulations, or populations.
A later trial phase can ask a more mature question, but it does not guarantee a positive result, regulatory approval, or relevance outside the studied population.
Randomized, double-blind, placebo-controlled parallel trial
Adults with early-stage type 2 diabetes inadequately controlled with diet and exercise
Under the efficacy estimand, HbA1c changed by -1.8 and -1.5 percentage points across the two CagriSema groups versus -0.1 with placebo. Body weight changed by -13.8% and -11.8% versus -1.4%.
Study administration: Once-weekly subcutaneous CagriSema at two trial dose levels or dose-matched placebo
Limitations: This was a comparatively small 40-week study in early-stage type 2 diabetes. The two trial arms are research methods, not consumer dosing options.
Randomized, double-blind, placebo- and active-controlled comparative trial
Adults with type 2 diabetes inadequately controlled on metformin with or without an SGLT2 inhibitor and BMI of at least 25
For the primary efficacy estimand, HbA1c changed by -1.91 percentage points with CagriSema 2.4 mg/2.4 mg versus -1.75 with semaglutide 2.4 mg. The study also reported greater average weight reduction with the combination in the active comparison.
Study administration: Once-weekly subcutaneous CagriSema at two trial dose levels, semaglutide at two dose levels, cagrilintide, or placebo
Limitations: The absolute HbA1c difference versus semaglutide was modest, the trial was sponsor funded, and a published correction is linked to the article. Results apply to the studied diabetes population and protocols.
Randomized, double-blind, placebo-controlled multicenter trial
Adults with type 2 diabetes receiving stable daily basal insulin with or without metformin
HbA1c changed by -2.33 and -2.10 percentage points across the two CagriSema groups versus -0.66 with placebo. Body-weight reductions were approximately 10% to 12%, and no severe hypoglycemia was reported.
Study administration: Once-weekly subcutaneous CagriSema at two trial dose levels or dose-matched placebo added to basal insulin
Limitations: The study was 40 weeks and involved a defined basal-insulin population. It was not designed to establish long-term cardiovascular safety or broad use outside the trial setting.
Multicenter, randomized, double-blind, placebo-controlled and active-controlled parallel trial
Adults without diabetes with obesity, or overweight plus at least one obesity-related complication
Under the treatment-policy estimand, mean body-weight change was -20.4% with CagriSema versus -3.0% with placebo at week 68. Gastrointestinal adverse events were reported by 79.6% versus 39.9% and were mainly transient and mild to moderate.
Study administration: Once-weekly subcutaneous CagriSema, semaglutide, cagrilintide, or placebo, all with lifestyle intervention
Limitations: The primary published comparison was CagriSema versus placebo in adults without diabetes. Group averages do not predict individual results, and 68 weeks does not resolve long-term cardiovascular outcomes, rare events, or durability after discontinuation.
Multicenter, randomized, double-blind, placebo-controlled trial
Adults with overweight or obesity and type 2 diabetes, HbA1c 7% to 10%
Mean body-weight change under the treatment-policy estimand was -13.7% with CagriSema versus -3.4% with placebo. HbA1c of 6.5% or less was reached by 73.5% versus 15.9%.
Study administration: Once-weekly subcutaneous CagriSema or placebo, with lifestyle intervention
Limitations: This trial studied a defined type 2 diabetes population for 68 weeks. It does not establish an approved indication, individual outcome, or long-term cardiovascular and renal benefit.
Prespecified secondary and post hoc analysis of REDEFINE 1
REDEFINE 1 adults without diabetes with obesity or overweight plus a complication
Blood pressure changed by -10.9/-5.4 mm Hg with CagriSema versus -2.8/-1.7 mm Hg with placebo at week 68.
Study administration: CagriSema, semaglutide, cagrilintide, or placebo
Limitations: This was a secondary and post hoc analysis, not a dedicated cardiovascular-outcomes trial or evidence of an approved hypertension indication. Weight loss may mediate part of the observed change.
Safety snapshot
Gastrointestinal effects were the most common adverse-event category across the pivotal CagriSema trials.
Controlled human evidenceCompleted trials do not eliminate uncertainty about rare events, longer exposure, broader populations, or risks after widespread use.
Open sourceGastrointestinal effects were the most common adverse-event category across the pivotal CagriSema trials.
Controlled human evidenceThe stated frequency is source-, product-, population-, route-, dose-, comparator-, and duration-specific; it is not a universal incidence estimate.
Open sourceNo source-qualified compound-specific warning or contraindication is encoded in the current record.
Evidence boundaryInvestigational; U.S. new drug application submitted in December 2025, with no FDA approval identified through July 25, 2026 The FDA decision and final label, long-term cardiovascular and renal outcomes, rare adverse events, durability after discontinuation, and how outcomes compare across broader populations.
Under the treatment-policy estimand, mean body-weight change was -20.4% with CagriSema versus -3.0% with placebo at week 68. Gastrointestinal adverse events were reported by 79.6% versus 39.9% and were mainly transient and mild to moderate.
Controlled human evidenceStudy discontinuation describes what happened under a study protocol; it is not an emergency-action threshold.
Open sourceNo compound-specific patient-facing urgent-action threshold is established in the current Relay record.
Evidence boundaryRelay does not infer emergency guidance from study discontinuations, mechanism, or incomplete adverse-event reporting.
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