CagriSema

Current status

On October 2, 2026 official records showed no exact US approval or label record for the combination. Novo Nordisk says US and Canadian applications were filed in December 2025; Health Canada lists the product under review.^{1531,1532,1533,1534}

How to read the results

REDEFINE trials focus on weight management and cardiovascular outcomes. REIMAGINE trials study type 2 diabetes in several treatment settings. Results depend on the population, comparison, dose, duration and analysis. All doses here describe study treatment.^{1533,1535,1536}

Weight loss in REDEFINE 1

CagriSema		20.4%
Semaglutide		14.9%
Cagrilintide		11.5%
Placebo		3%

% of starting body weight. 3,417 adults with overweight or obesity, without diabetes. Weekly subcutaneous CagriSema targeted 2.4 mg of each component; lifestyle intervention was provided.¹⁵²⁹

Why another headline says 22.7%

The treatment-policy analysis accounts for treatment discontinuation and gives 20.4% average loss with CagriSema. The trial-product analysis estimates outcomes with continued assigned treatment and gives 22.7%, versus 16.1% with semaglutide, 11.8% with cagrilintide and 2.3% with placebo.^1529,1537

With type 2 diabetes

REDEFINE 2 randomized 1,206 adults with type 2 diabetes. Treatment-policy weight change at week 68 was -13.7% with CagriSema and -3.4% with placebo.¹⁵³⁸

Comparisons with tirzepatide

20.2% vs 23.6%

The sponsor reports that CagriSema missed the noninferiority objective against tirzepatide in an open-label obesity trial of 809 adults.^1539,1540

The doses and analysis

CagriSema 2.4/2.4 mg was compared with tirzepatide 15 mg. Weight change was -20.2% versus -23.6% in the treatment-regimen analysis and -23.0% versus -25.5% in the efficacy analysis.¹⁵³⁹

REIMAGINE 5 comparator

In type 2 diabetes, the sponsor reported -12.4% versus -9.1% weight change at week 60 with CagriSema 1.0/1.0 mg versus tirzepatide 5 mg. HbA1c fell 1.71 versus 1.67 percentage points. Detailed uncertainty and safety tables remain pending.^1541,1542

Glucose control and remission

Early type 2 diabetes

REIMAGINE 1 randomized 189 adults managed with diet and exercise. At week 40, efficacy-analysis HbA1c changes were -1.8, -1.5 and -0.1 percentage points with CagriSema 2.4/2.4 mg, 1.0/1.0 mg and placebo. Weight changes were -13.8%, -11.8% and -1.4%.¹⁵³⁰

53.0% vs 20.1%

REIMAGINE 1 assessed HbA1c below 6.5% with no glucose-lowering medication at week 52. Estimated proportions were 53.0% with CagriSema 2.4/2.4 mg, 42.0% with 1.0/1.0 mg and 20.1% with placebo. This supportive endpoint was not adjusted for multiple comparisons.¹⁵³⁰

Other diabetes settings

REIMAGINE 2 studied 2,713 adults using metformin with or without an SGLT2 inhibitor. REIMAGINE 3 studied 274 adults using basal insulin. Both reported greater glucose lowering with CagriSema than their respective comparisons.^1543,1544

Appetite, muscle and bone

The year-long appetite study

A randomized study of 130 adults measured appetite, food intake, eating behavior and brain responses to food cues. At week 52, the estimated appetite-score change was -23.31 mm with CagriSema and -3.76 mm with placebo; weight change was -23.41% versus -1.04%.¹⁵⁴⁵

Muscle volume fell with weight loss

In the small REIMAGINE 1 MRI substudy, fat-free contractile thigh muscle volume changed -11.0%, -8.6% and -1.4% at week 40 with CagriSema 2.4/2.4 mg, 1.0/1.0 mg and placebo. There were 81 baseline scans and fewer follow-up measurements. Strength and muscle volume are different outcomes.¹⁵⁴⁶

Bone questions remain

A REIMAGINE 2 analysis measured CTX-1 and P1NP bone-turnover markers. It did not measure fractures, bone strength or bone mineral density. A separate bone-metabolism trial is recruiting.^1547,1548

Safety and open questions

Digestive adverse events

Gastrointestinal events affected 79.6% of CagriSema participants versus 39.9% with placebo in REDEFINE 1, and 72.5% versus 34.4% in REDEFINE 2. Most were described as transient and mild or moderate.^1529,1538

Stopping because of side effects

A REDEFINE 1 poster reports 5.9% discontinued CagriSema because of gastrointestinal adverse events. In the smaller appetite study, adverse events led to treatment withdrawal in 12 of 66 CagriSema participants versus 2 of 64 with placebo.^1549,1545

Longer-term outcomes

Cardiovascular-event results and completed chronic-kidney-disease trial results remain pending in the registry. Longer-term weight after stopping, pregnancy outcomes and combination-specific interaction results are also unresolved.^{1550,1551,1530,1552}

Product identity

The trials used controlled study product. FDA states that cagrilintide is not a component of an approved drug and cannot be used in compounding under federal law. Trial results do not authenticate other products carrying the same name.¹⁵⁵³

Identity, access and trial treatment

01 What is CagriSema, and how is it different from either component alone?

CagriSema is the investigational fixed-dose combination of cagrilintide, a long-acting amylin receptor agonist, and semaglutide, a GLP-1 receptor agonist. Its clinical program studies the two components together in once-weekly subcutaneous injections.^{1554,1555,1535}

02 Is CagriSema approved in the United States or Canada?

CagriSema remained investigational on October 2, 2026; official FDA approval and label searches returned no exact combination record. Novo Nordisk says it filed US and Canadian applications in December 2025. Health Canada lists the combination under review, with the submission accepted in March 2026.^{1531,1532,1533,1534}

03 Is there an official price or established insurance coverage for CagriSema?

An official US CagriSema price and established product-specific insurance terms were not found in the cited sources. The combination remains investigational. Price and coverage will depend on a marketed product, its approved uses and individual plans.^1531,1532

04 How does the trial product differ from products sold online as CagriSema?

The trials used protocol-controlled study product. They do not authenticate products sold under the same name. FDA states that cagrilintide cannot be used in compounding under federal law and is not a component of an FDA-approved drug.^1553,1529

05 What product handling or stability information is actually public?

The published device study tested a dual-chamber pen in simulated use after training, without administering the drug. Public storage and stability instructions for an approved US CagriSema product were not available in the cited records.^1556,1532

06 What doses were used in the trials?

The main trials used once-weekly subcutaneous injections. REDEFINE 1 and 2 targeted 2.4 mg cagrilintide plus 2.4 mg semaglutide. REIMAGINE 1 to 3 also studied 1.0 mg plus 1.0 mg. REDEFINE 4 compared the 2.4/2.4 mg combination with tirzepatide 15 mg; REIMAGINE 5 compared 1.0/1.0 mg with tirzepatide 5 mg. Trial protocols included dose escalation and allowed adjustments.^{1529,1538,1530,1543,1544,1539,1541}

07 Has switching directly from semaglutide to CagriSema been studied?

A recruiting phase 3 study plans to compare three switch regimens in 210 participants previously treated with semaglutide. It has no posted results, so the current evidence does not establish a switch schedule or its tolerability.¹⁵⁵⁷

08 What is the difference between the REDEFINE and REIMAGINE programs?

REDEFINE studies weight management and cardiovascular outcomes in people with obesity or overweight. REIMAGINE studies type 2 diabetes, including people using diet and exercise, oral medicines or basal insulin. Each trial has its own population, doses, comparison and outcome.^{1533,1535,1558,1550,1559,1536,1560}

09 How do the two components work?

Semaglutide activates GLP-1 receptors. Cagrilintide acts at amylin receptors and also activates the calcitonin receptor in laboratory studies. The combination aims to influence appetite and glucose control through both components. Human outcome trials measure the combined clinical effect.^{1561,1529,1530}

10 How long do the components stay in the body?

In the phase 1b combination study, cagrilintide had a terminal half-life of 159 to 195 hours and semaglutide 145 to 165 hours across the studied cohorts. These are separate component measurements. The trial used weekly injections. Those half-lives provide no tested washout or switching schedule.¹⁵⁶²

Weight, appetite and body composition

01 What did REDEFINE 1 report for weight loss?

REDEFINE 1 randomized 3,417 adults without diabetes. At week 68, average weight change was -20.4% with CagriSema, -14.9% with semaglutide, -11.5% with cagrilintide and -3.0% with placebo in the treatment-policy analysis, which accounts for stopping treatment. The analysis estimating outcomes if participants continued assigned treatment gave -22.7%, -16.1%, -11.8% and -2.3%, respectively.^1529,1537

02 Did REDEFINE 1 prove that the two drugs are synergistic?

CagriSema produced greater average weight loss than either component in REDEFINE 1. The randomized comparison supports an added benefit from using the components together. Molecular synergy was not an endpoint of that trial.^1529,1537

03 What did REDEFINE 2 show in adults with type 2 diabetes?

REDEFINE 2 randomized 1,206 adults with type 2 diabetes. At week 68, treatment-policy mean weight change was -13.7% with CagriSema and -3.4% with placebo. HbA1c at or below 6.5% was estimated for 73.5% versus 15.9%. The trial had no separate component arms.^1538,1558

04 Do the trials show when weight loss plateaus or who will not respond?

The trials report group weight trajectories and final responder thresholds. They have not established a reliable personal plateau, a stopping rule for a short stall, or a way to predict an individual final result.¹⁵²⁹

05 What did studies measure about appetite, cravings, or food noise?

In a randomized year-long study, CagriSema reduced post-meal appetite ratings and food intake. At week 52, the estimated appetite-score change was -23.31 mm with CagriSema and -3.76 mm with placebo. Energy-intake change was -3,262 kJ versus +130 kJ. Researchers also measured eating behavior and brain responses to food cues.^1545,1563

06 How much weight was lost in the year-long appetite study?

The presentation reports estimated weight change of -23.41% with CagriSema and -1.04% with placebo at week 52. It randomized 130 adults selected for overweight or obesity and higher eating disinhibition, without diabetes. This was a smaller, selected population than REDEFINE 1.¹⁵⁴⁵

07 What did the clinical study find about gastric emptying?

In a 62-person randomized study assessed at week 20, CagriSema reduced ad libitum energy intake and improved appetite measures versus placebo. A paracetamol absorption test found no delay in gastric emptying under those study conditions. That result is specific to this test and time point.^1564,1565

08 What do the MRI data show about muscle and body composition?

The REIMAGINE 1 MRI substudy found loss of both fat and muscle volume. At week 40, total thigh muscle volume changed -11.9%, -9.4% and -1.9% with CagriSema 2.4/2.4 mg, CagriSema 1.0/1.0 mg and placebo. Fat-free contractile muscle volume changed -11.0%, -8.6% and -1.4%. Only 81 people had baseline MRI scans, with fewer measured at week 40. A dedicated muscle-health trial is recruiting.^{1546,1530,1559,1566}

09 Do the current data show that CagriSema protects bone?

The REIMAGINE 2 poster reports changes in CTX-1 and P1NP, which are bone-turnover biomarkers. It reports no bone mineral density, fracture, or bone-strength outcome. A separate bone-metabolism trial is recruiting, so clinical bone protection is unresolved.^1547,1548

10 What did the lower-dose REDEFINE 9 trial report?

Novo Nordisk reported average weight change of -21.0% with CagriSema 1.0/1.0 mg and -2.0% with placebo at week 68 in adults with obesity. REDEFINE 9 also studied 1.7/1.7 mg, but this release reports the 1.0/1.0 mg comparison. Detailed uncertainty estimates and safety rates remain pending.^1541,1567

11 Does the dose analysis prove that lower doses work just as well?

No. A REDEFINE 1 analysis grouped participants by the dose they actually received after randomization. Average weight loss was similar across those groups, but dose changes could depend on response and side effects. In the full CagriSema arm, 57.4% were taking 2.4/2.4 mg at week 68 and 74.7% had reached that dose at some point.¹⁵⁴⁹

12 Was CagriSema tested in East Asian adults?

Yes. REDEFINE 5 randomized 331 adults in Japan and Taiwan, including 80 with type 2 diabetes. At week 68, estimated weight change was -18.4% with CagriSema 2.4/2.4 mg and -11.9% with semaglutide 2.4 mg in the trial-product analysis. The difference was -6.5 percentage points (95% CI -8.4 to -4.6). Both groups received lifestyle intervention.¹⁵⁷⁵

Diabetes trials and comparisons

01 What did REDEFINE 4 report against tirzepatide?

CagriSema did not meet the noninferiority objective against tirzepatide in the sponsor-reported REDEFINE 4 results, an open-label trial of 809 adults with obesity over 84 weeks. For CagriSema 2.4/2.4 mg versus tirzepatide 15 mg, average weight change was -20.2% versus -23.6% in the treatment-regimen analysis and -23.0% versus -25.5% in the efficacy analysis. Detailed results remain unpublished in the cited materials.^1539,1540

02 Why do REDEFINE 4 and REIMAGINE 5 give different tirzepatide comparisons?

The trials tested different doses in different populations. REDEFINE 4 compared CagriSema 2.4/2.4 mg with tirzepatide 15 mg in obesity over 84 weeks. REIMAGINE 5 compared CagriSema 1.0/1.0 mg with tirzepatide 5 mg in type 2 diabetes over 60 weeks. Its participants used metformin with or without an SGLT2 inhibitor. Read each result with its own dose and population.^{1539,1540,1541,1542}

03 What did REIMAGINE 1 report?

REIMAGINE 1 randomized 189 adults with early type 2 diabetes managed with diet and exercise. At week 40, efficacy-estimand HbA1c changes were -1.8, -1.5, and -0.1 percentage points with CagriSema 2.4/2.4 mg, CagriSema 1.0/1.0 mg, and placebo. Weight changes were -13.8%, -11.8%, and -1.4%.^1530,1559

04 What did REIMAGINE 2 report?

REIMAGINE 2 randomized 2,713 adults with type 2 diabetes on metformin with or without an SGLT2 inhibitor. The primary efficacy-estimand HbA1c change was -1.91 percentage points with CagriSema 2.4/2.4 mg and -1.75 with semaglutide 2.4 mg, a difference of -0.16 points. The trial also included CagriSema 1.0/1.0 mg, semaglutide 1.0 mg, cagrilintide 2.4 mg, and placebo arms.^1543,1536

05 What did REIMAGINE 3 report for people using basal insulin?

REIMAGINE 3 randomized 274 adults with type 2 diabetes using basal insulin with or without metformin. At week 40, HbA1c changes were -2.33 and -2.10 points with the two CagriSema doses versus -0.66 with placebo. The abstract reports 10% to 12% weight reduction and no severe hypoglycaemia.^1544,1560

06 What is known about REIMAGINE 4?

REIMAGINE 4 compared CagriSema 2.4/2.4 mg with tirzepatide 15 mg in adults with type 2 diabetes treated with metformin with or without an SGLT2 inhibitor. The registry lists 1,024 actual participants and completed status, with no posted results. A numerical result remains pending primary release or publication.^1568,1533

07 What did the REIMAGINE 5 topline say?

Novo Nordisk reported average weight change of -12.4% with CagriSema 1.0/1.0 mg and -9.1% with tirzepatide 5 mg at week 60 in REIMAGINE 5. HbA1c changed -1.71 and -1.67 percentage points. The sponsor reports superiority for weight loss and noninferiority for HbA1c. The release gives no confidence intervals, P values or arm-specific safety tables.^1541,1542

08 Are there results for CagriSema in chronic kidney disease?

A 626-person phase 2 trial compared CagriSema with semaglutide, cagrilintide, and placebo in people with chronic kidney disease, type 2 diabetes, and excess weight. The registry lists completed status but no posted results, so kidney efficacy and safety remain pending.¹⁵⁵¹

09 Has CagriSema been shown to reduce cardiovascular events?

The REDEFINE 3 cardiovascular-outcomes trial lists 7,101 actual participants and active, not recruiting status. It has no posted results in the captured registry record, so fewer cardiovascular events have not been established.¹⁵⁵⁰

10 What did the earlier 92-person diabetes trial find?

After 32 weeks, average weight change was -15.6% with CagriSema, -5.1% with semaglutide and -8.1% with cagrilintide, each component targeted at 2.4 mg weekly. HbA1c fell 2.2, 1.8 and 0.9 percentage points. The HbA1c difference between CagriSema and semaglutide did not reach statistical significance (P=0.075).^1569,1570

11 What did continuous glucose monitoring show?

In a REIMAGINE 2 subgroup of 1,298 participants, observed time in the glucose range 3.9 to 10 mmol/L at week 68 was 87.9% with CagriSema 2.4/2.4 mg, 86.2% with semaglutide 2.4 mg, 69.0% with cagrilintide and 64.0% with placebo. This was a subgroup analysis within the main trial.^1571,1543

12 How many people reached both glucose and weight targets?

A REIMAGINE 1 post hoc analysis estimated that 62% with CagriSema 2.4/2.4 mg reached HbA1c below 7% and lost at least 10% of body weight at week 40, versus 3% with placebo. These were modeled proportions across several combined targets. They were not raw responder counts or a separate trial.^1572,1530

13 Has CagriSema been tested for MASH or liver fibrosis?

A 52-week MASH trial included an exploratory CagriSema 2.4/2.4 mg arm with 99 participants within a seven-arm study of 698 people. The abstract reports no substantial difference from placebo in improvement of liver fibrosis without worsening MASH. This exploratory comparison supplies limited evidence for liver disease; reductions in liver fat are a separate outcome.^1576,1577

Side effects and special situations

01 How common were gastrointestinal adverse events in the main trials?

In REDEFINE 1, gastrointestinal events occurred in 79.6% of CagriSema participants and 39.9% of placebo participants. In REDEFINE 2, the rates were 72.5% and 34.4%. Both reports describe most events as transient and mild or moderate.^1529,1538

02 What do the trials show about serious events and treatment withdrawal?

A REDEFINE 1 poster reports that 5.9% stopped CagriSema because of gastrointestinal adverse events. In the separate 130-person appetite study, serious adverse events affected 3 of 66 CagriSema participants and 4 of 64 placebo participants. Adverse events led to treatment withdrawal in 12 of 66 and 2 of 64. These figures describe different cohorts and outcomes.^{1529,1549,1545}

03 Did controlled studies establish fatigue, sleep, or mood effects?

Fatigue and depressed mood appear among individual reasons for stopping treatment in the year-long appetite study. The presentation leaves causation uncertain and gives no controlled rate for mood or fatigue. Sleep was not a reported outcome.¹⁵⁴⁵

04 What is known about injection-site or allergic reactions?

In the 92-person phase 2 diabetes trial, two participants in the cagrilintide-only arm had 21 injection-site reaction events. That finding does not supply a CagriSema rate. A reliable combination-specific severe allergic-reaction estimate was not available in the cited primary tables.¹⁵⁶⁹

05 Was hair loss measured in controlled CagriSema trials?

A controlled CagriSema hair-loss rate was not found in the cited primary materials. The question remains open.^{1529,1538,1530,1543,1544}

06 What is known about pregnancy or breastfeeding?

REIMAGINE 1 excluded participants who were pregnant, breastfeeding or intended to become pregnant. It required pregnancy testing and stopped study treatment if pregnancy occurred or was suspected. That trial supplies no direct pregnancy or breastfeeding outcome evidence. A combination-specific clinical washout recommendation is not established by this packet.¹⁵³⁰

07 Has CagriSema been studied with warfarin or atorvastatin?

A completed 34-person study examined how CagriSema affects atorvastatin and warfarin levels in the blood. Its registry record has no posted results. Interaction findings for the combination remain pending.¹⁵⁵²

Onset and treatment follow-up

01 How quickly did CagriSema start working in trials?

Appetite and food intake were measured at week 20 in one study; the year-long appetite study assessed outcomes at weeks 22 and 52. Main diabetes trials reported outcomes at week 40, and the main obesity trials at weeks 68 or 84. These scheduled assessments do not give a reliable personal onset time.^{1564,1545,1530,1544,1529,1538,1539}

02 What happens to weight after CagriSema is stopped?

Post-treatment weight maintenance is still a major open question. REDEFINE 1 reports its 68-week treatment results, while its longer off-treatment extension has not reported results in the cited materials. REIMAGINE 1 followed participants for 12 weeks after treatment stopped, but the accessible supplement text does not give a numerical week-52 weight result.^{1529,1535,1549,1530}

03 Are longer-term weight-maintenance studies underway?

Yes. NCT07011667 lists 609 actual participants and an active, not recruiting main and extension study. NCT06780449 lists a 104-week main phase plus a one-year extension and remains active, not recruiting, with estimated enrollment of 400. Neither captured registry record has results.^1573,1574

04 Did diabetes remission last after treatment stopped?

REIMAGINE 1 assessed remission 12 weeks after study treatment stopped: HbA1c below 6.5% with no glucose-lowering medication at the assessment. Estimated proportions meeting that target were 53.0% after CagriSema 2.4/2.4 mg, 42.0% after 1.0/1.0 mg and 20.1% after placebo. This supportive endpoint was not adjusted for multiple comparisons. Longer-term remission is unknown.¹⁵³⁰