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Weight loss

CagriSema, explained simply

Cagrilintide and semaglutide together in one weekly injection. In the phase 3 REDEFINE 1 trial, people lost 20.4% of body weight over 68 weeks against 3.0% on placebo — 22.7% among those who stayed on treatment. Submitted to the US FDA in December 2025; not approved anywhere yet.

Well studied in peopleInjection under the skin (like insulin shots)9 cited sourcesResearch compound — not FDA approved

Start here

What is CagriSema?

CagriSema is Novo Nordisk's fixed-dose combination of two weekly injectables: cagrilintide, a long-acting copy of the fullness hormone amylin, and semaglutide, a GLP-1 (a gut hormone that tells your brain you're full) drug — 2.4 mg of each delivered together 1. It is the combination behind the '20%+ weight loss' headlines: in its main phase 3 trial, people lost 20.4% of body weight over 68 weeks against 3.0% on placebo 1. It is not approved anywhere yet; it was submitted to the US FDA in December 2025 9.

How it works in your body

CagriSema is two appetite signals in one weekly shot. Semaglutide copies GLP-1, a gut hormone that tells your brain you are full, slows your stomach, raises insulin and lowers glucagon 6. Cagrilintide copies amylin, a hormone released with insulin, which creates fullness through both the energy-balance and the reward regions of the brain 6. Together the two signals cut appetite more than either does alone — in the first combination trial, adding cagrilintide 2.4 mg to semaglutide meant 17.1% weight loss at 20 weeks against 9.8% on semaglutide alone 4.

Why researchers care

In REDEFINE 1, a phase 3 trial of 3,417 adults, CagriSema produced 20.4% weight loss at 68 weeks, against 14.9% for semaglutide alone, 11.5% for cagrilintide alone, and 3.0% for placebo — and 22.7% among people who took it as intended 1. In a 2,713-person head-to-head trial in type 2 diabetes, it lowered HbA1c (a blood test reflecting average blood sugar over about three months) more than semaglutide 2.4 mg 5. It is not approved anywhere yet; the US FDA filing for weight management was submitted in December 2025 9.

The deeper mechanism, for the curious

Semaglutide copies GLP-1 (a gut hormone that signals fullness). It acts on the appetite centers in the brain, tells the pancreas to release insulin only when blood sugar is high, lowers glucagon (a hormone that raises blood sugar), and slows how fast the stomach empties 6. Cagrilintide is a long-acting version of amylin (a hormone released with insulin that makes you feel full). It sends fullness signals through both the brain areas that control basic hunger and the areas that drive craving and reward 6. The REDEFINE 1 researchers credit the combination's effect to the two drugs acting in complementary ways in the hypothalamus (the brain's appetite control center), the hindbrain and the septum (other brain regions) 1. The two drugs do not get in each other's way in the body: cagrilintide levels rise in proportion to the dose and leave semaglutide levels and clearance unchanged. Half-lives (the time for half the drug to leave the body) are 159-195 hours for cagrilintide and 145-165 hours for semaglutide, which supports a once-weekly dose of both together 4.

Evidence check

Well studied in people

This has been through large human trials — the strongest kind of evidence. Scientists have tested it on many people and measured what actually happened.

Every numbered marker on this page links to one of the 9 sources at the bottom.

96/100

Weight Management

The largest weight reduction documented in this library: 20.4% at week 68 vs 3.0% on placebo in 3,417 adults (22.7% among those treated as intended); more than half (53.6%) lost at least 20% of body weight vs 1.9% on placebo.

90/100

Blood Sugar Control

HbA1c (3-month blood sugar average) fell 1.91 percentage points vs 1.75 on semaglutide 2.4 mg in 2,713 people with type 2 diabetes; about 3 in 4 (73.5%) reached an HbA1c of 6.5% or less vs 15.9% on placebo in 1,206 adults.

88/100

Appetite Control

Two complementary satiety hormones — amylin through homeostatic and hedonic brain regions, GLP-1 through the hypothalamus — with an apparently additive effect on appetite reduction.

What the research points to

The most-asked question

How much CagriSema do I take?

CagriSema is dose-escalated: the studies start everyone low and step the dose up on a schedule, so the right amount depends on the week you're on. The research-reported maintenance range is 0.25–2.4 mg, once weekly.

  1. Weeks 1-4 — escalation step 1

    0.25 mg each

    • How often
      Once weekly
    • Used for
      Starting the escalation
    • How
      Injection under the skin

    Both phase 3 REDEFINE trials initiated the fixed-dose pen at 0.25 mg of each drug 1. Escalation step 1 in the trial protocol, held 4 weeks 7. Human trials; 2,108 participants took the combination in REDEFINE 1 alone 1.

  2. Weeks 5-8 — escalation step 2

    0.5 mg each

    • How often
      Once weekly
    • Used for
      Escalation
    • How
      Injection under the skin

    Escalation step 2 in the trial protocol, held 4 weeks 7. The same participants stepped up from 0.25 mg — this is a true titration (stepping the dose up gradually) ladder, confirmed from the protocol and trial methods 17.

  3. Weeks 9-12 — escalation step 3

    1.0 mg each

    • How often
      Once weekly
    • Used for
      Escalation, Studied as its own maintenance dose
    • How
      Injection under the skin

    Escalation step 3 in the trial protocol, held 4 weeks 7. Also studied as a maintenance dose in its own right: REIMAGINE 2 carried a cagrilintide-semaglutide 1.0 mg each arm of 595 people with type 2 diabetes for 68 weeks 5.

  4. Weeks 13-16 — escalation step 4

    1.7 mg each

    • How often
      Once weekly
    • Used for
      Escalation
    • How
      Injection under the skin

    Escalation step 4 in the trial protocol, held 4 weeks before the maintenance dose 7.

  5. Week 17 on — maintenance (52 weeks in phase 3)

    2.4 mg each

    • How often
      Once weekly
    • Used for
      Maintenance, The dose in every phase 3 trial
    • How
      Injection under the skin

    The maintenance dose in every phase 3 trial: 2.4 mg of each drug from week 16, held through a 52-week maintenance period in REDEFINE 1 1. Investigators could delay escalation or reduce the dose, and participants could stay on a submaximum dose — at week 68, 57.4% of the combination group was on the maximum dose, against 70.9% on semaglutide alone, 82.5% on cagrilintide alone and 70.6% on placebo 1. Missed doses restarted one step lower per the protocol rules 7.

Adjusting your dose

You're at the right dose if…

Consider going up if…

Go down if…

The ceiling: 2.4 mg of each drug once weekly

Injection sites & technique

Where do I inject CagriSema?

The best spots

  • Abdomen
  • Thigh
  • Upper arm

How to do it, step by step

Injection under the skin

Timing

When do I take CagriSema?

Best time of day

Once weekly on a fixed dosing day — the trials scheduled a dosing day and defined catch-up rules around it 7.

With or without food?

The semaglutide component is injected without regard to meals 8.

Taking it with other peptides

This IS the stack — cagrilintide (a long-acting amylin-type appetite hormone) and semaglutide (a GLP-1 (a gut hormone that tells your brain you're full) drug) were raised together, step by step, in every trial 3. Trials did not allow combining with any other GLP-1 receptor agonist (a drug that mimics the gut's fullness hormone), DPP-4 inhibitor (another type of diabetes drug), or amylin analogue (a modified version of a natural molecule) 7.

The honest list

What side effects could CagriSema cause?

Common — usually mild

These show up most often. They usually fade as your body adjusts.

Less common

Worth knowing about, but most people never see these.

Serious — stop and get medical help

Rare, but if any of these happen, stop and contact a medical professional.

Week by week

What should I expect from CagriSema, and when?

  1. Weeks 1-16

    You might notice
    What's normal
    What's next

  2. Weeks 17-32

    You might notice
    What's normal
    What's next

  3. Weeks 33-68

    You might notice
    What's normal
    What's next

How to tell it's actually working

physical

clinical

subjective

Not seeing anything? The usual reasons

Is it right for you?

Who should avoid CagriSema?

Do not use it if…

Be extra careful if…

When to stop

CagriSema is an investigational combination with no approved label anywhere. These stop rules are the ones its own trials used, plus the semaglutide component label — they are not medical advice. Decisions about starting, changing, or stopping belong with a qualified clinician.

What it mixes badly (and well) with

Medications

  • Check first
    Insulin and sulfonylureas — increased hypoglycaemia risk; the semaglutide label advises considering dose reductions [8]
  • Check first
    Rescue diabetes medication in trials excluded GLP-1 receptor agonists, DPP-4 inhibitors and amylin analogues [7]

Other peptides

  • Check first
    Other GLP-1 receptor agonists, DPP-4 inhibitors, and amylin analogues (such as pramlintide) — trials prohibited these combinations [7]

Who it tends to suit

Weight management

About 1 in 5 pounds of body weight lost (20.4%) over 68 weeks against 3.0% on placebo, and 22.7% among people treated as intended — shown in 3,417 adults without diabetes 1.

Type 2 diabetes with excess weight

13.7% weight loss against 3.4% on placebo at 68 weeks, and about 3 in 4 people (73.5%) reached an HbA1c (3-month blood sugar average) of 6.5% or less against 15.9% on placebo — shown in 1,206 adults 2.

When semaglutide alone is not enough

Head-to-head at the same dose, the combination lost 5.5 percentage points more weight than semaglutide alone and 8.9 more than cagrilintide alone 1; in 2,713 people with type 2 diabetes it also beat semaglutide 2.4 mg on HbA1c (the 3-month blood sugar average) 5.

The safety picture overall

The safety picture comes from randomised trials with over 4,000 participants exposed to the combination 1235. In REDEFINE 1 (3,417 adults without diabetes), about 4 in 5 people on CagriSema (79.6%) had gastrointestinal events — nausea, vomiting, diarrhoea, constipation or abdominal pain — against about 2 in 5 on placebo (39.9%); most were transient and mild to moderate, peaked during dose escalation, and eased once escalation ended 1. Any adverse event: 92.3% vs 82.3% on placebo; serious adverse events: about 1 in 10 (9.8%) vs 6.1% on placebo, most commonly hepatobiliary and gastrointestinal disorders; discontinuation of an active drug for adverse events: 5.9% vs 3.5% 1. Two deaths occurred among the 2,108 people in the combination group; the adjudicated causes were suicide and cancer, and mental-health scores (C-SSRS, PHQ-9) were similar across all four groups throughout the trial 1. In type 2 diabetes the pattern held: gastrointestinal events 72.5% vs 34.4% on placebo (REDEFINE 2, 1,206 adults) 2; adverse events 86.9% on the full dose vs 81.2% on semaglutide 2.4 mg alone and 70.5% on placebo (REIMAGINE 2, 2,713 adults) 5. Heart rate rose slightly (+0.94 beats per minute at week 68, vs +1.17 on semaglutide, -3.31 on cagrilintide and -0.58 on placebo) 1. In the 32-week phase 2 diabetes trial no level 2 or 3 hypoglycaemia and no fatal events were reported 3.

Phase 3 evidence across REDEFINE 1 1, REDEFINE 2 2 and REIMAGINE 2 5, plus the phase 2 3 and phase 1b 4 trials. CagriSema is not approved anywhere; the US FDA weight-management filing was submitted in December 2025 9. Because no CagriSema label exists, the contraindication and interaction statements on this page rest on the semaglutide component's approved label 8 and the trial protocol rules 7.

Not our opinion — the published record

What the studies actually found about CagriSema

2025

Coadministered Cagrilintide and Semaglutide in Adults with Overweight or Obesity (REDEFINE 1)

The main phase 3a obesity trial: 3,417 adults without diabetes were randomly split 21:3:3:7 into four groups: cagrilintide-semaglutide 2.4 mg each, semaglutide 2.4 mg, cagrilintide 2.4 mg, or placebo (a dummy treatment), for 68 weeks. Weight changed by -20.4% on the combination, -14.9% on semaglutide, -11.5% on cagrilintide and -3.0% on placebo. Counting only people who took the drug as intended, the combination reached -22.7%. More than half (53.6%) lost at least 20% of their body weight, against 1.9% on placebo. The fixed-dose pen started at 0.25 mg of each drug and went up every 4 weeks to 2.4 mg by week 16, then stayed there for 52 weeks.

Garvey WT, Blüher M, Osorto Contreras CK, et al.

2025

Cagrilintide-Semaglutide in Adults with Overweight or Obesity and Type 2 Diabetes (REDEFINE 2)

Phase 3a trial in 12 countries: 1,206 adults with type 2 diabetes and a BMI (a weight-for-height measure) of 27 or more were randomly assigned, 3 to 1, to cagrilintide-semaglutide 2.4 mg each or placebo for 68 weeks. Weight changed by -13.7% vs -3.4% on placebo. 73.5% reached an HbA1c (a blood test that shows average blood sugar over about 3 months) of 6.5% or less vs 15.9% on placebo. Stomach and gut side effects: 72.5% vs 34.4%, mostly short-lived and mild or moderate.

Davies MJ, Bajaj HS, Broholm C, et al.

2023

Efficacy and safety of co-administered once-weekly cagrilintide 2.4 mg with once-weekly semaglutide 2.4 mg in type 2 diabetes

The 32-week phase 2 trial: 92 adults with type 2 diabetes on metformin (a common diabetes pill), with or without an SGLT2 inhibitor (another diabetes pill), were randomly split evenly into three groups: CagriSema, semaglutide, or cagrilintide (all raised to 2.4 mg), given as separate same-day injections. HbA1c (average blood sugar over about 3 months) fell 2.2 percentage points on CagriSema vs 1.8 on semaglutide and 0.9 on cagrilintide; weight fell 15.6% vs 5.1% and 8.1%. Time spent in the target blood sugar range rose from 45.9% to 88.9% on CagriSema. Side effects: 68% vs 71% and 80% by group; no deaths.

Frias JP, Deenadayalan S, Erichsen L, et al.

2021

Safety, tolerability, pharmacokinetics, and pharmacodynamics of concomitant administration of multiple doses of cagrilintide with semaglutide 2.4 mg

The first human trial of the combination, with 95 adults exposed: six groups were randomly split 3 to 1 into cagrilintide 0.16-4.5 mg or placebo, all with semaglutide 2.4 mg, with doses stepped up together every 4 weeks over 16 weeks. At week 20, weight fell 17.1% with cagrilintide 2.4 mg plus semaglutide vs 9.8% on semaglutide plus placebo. Cagrilintide levels in the blood rose in proportion to the dose and did not change semaglutide levels. Half-lives (the time for half the drug to leave the body) were 159-195 hours for cagrilintide and 145-165 hours for semaglutide.

Enebo LB, Berthelsen KK, Kankam M, et al.

2026

Cagrilintide-semaglutide (CagriSema) versus semaglutide or cagrilintide in people with type 2 diabetes (REIMAGINE 2)

Phase 3 head-to-head trial in 2,713 people with type 2 diabetes on metformin with or without an SGLT2 inhibitor, across 30 countries for 68 weeks. HbA1c (average blood sugar over about 3 months) fell 1.91 percentage points on cagrilintide-semaglutide 2.4 mg each vs 1.75 on semaglutide 2.4 mg (difference -0.16, p=0.0035; a p-value this small means the gap is unlikely to be chance). A 1.0 mg each group (595 people) was also studied. Side effects: 86.9% on the full-dose combination vs 81.2% on semaglutide 2.4 mg and 70.5% on placebo, mostly stomach and gut problems.

Buse JB, Bajaj HS, Dalskov SM, et al.

2024

Cagrilintide: A Long-Acting Amylin Analog for the Treatment of Obesity

Expert-reviewed paper on why the two drugs are combined: amylin, a hormone released with insulin from the pancreas, makes you feel full by acting on both the brain areas that control basic hunger and those that drive craving and reward. Semaglutide cuts appetite through GLP-1 receptors (docking sites for a gut hormone) in the brain's appetite center, raises insulin, lowers glucagon, and slows how fast the stomach empties. The two separate but related routes appear to add up for cutting appetite.

D'Ascanio AM, Mullally JA, Frishman WH

2021

Novo Nordisk trial protocol NN9838-4862: co-administration of cagrilintide s.c. 2.4 mg and semaglutide s.c. 2.4 mg (posted on ClinicalTrials.gov, NCT04982575)

The official trial plan with the dose-increase table: step 1 0.25 mg, step 2 0.5 mg, step 3 1.0 mg, step 4 1.7 mg, 4 weeks each, then the 2.4 mg maintenance dose from week 16, for both drugs together. It also sets rules for missed doses (restart one step lower after 3-4 weeks missed, two steps lower after 4-5, from the lowest dose after 5+), rules for changing doses, and a ban on combining with other GLP-1 receptor agonists (drugs like semaglutide), DPP-4 inhibitors (another class of diabetes pills), or amylin analogues (drugs that copy amylin).

Novo Nordisk A/S

2024

WEGOVY (semaglutide) injection — Prescribing Information

The approved US label for the semaglutide part. Boxed warning (the strongest FDA warning): semaglutide causes thyroid C-cell tumors in rodents at doses relevant to people. Do not use it with a personal or family history of medullary thyroid carcinoma (a rare thyroid cancer) or MEN 2 (an inherited condition that causes tumors in hormone glands), or after a serious allergic reaction to semaglutide. Injection sites: belly, thigh, or upper arm. It warns of a higher risk of hypoglycaemia (dangerously low blood sugar) when combined with insulin or a sulfonylurea (a diabetes pill), and of a temporary worsening of diabetic retinopathy (eye damage from diabetes) when blood sugar improves quickly.

Novo Nordisk / U.S. FDA (DailyMed)

2025

Novo Nordisk company announcement: CagriSema regulatory submission

CagriSema for weight management was submitted to the US FDA in December 2025, based on the REDEFINE 1 and REDEFINE 2 main trials. For type 2 diabetes, Novo Nordisk says it will approach regulators to discuss the approval route after the REIMAGINE 1 and REDEFINE 3 results. This is the company's own statement, the main public source for filing status.

Novo Nordisk A/S (company announcement — not peer-reviewed)

If this isn't the right fit

What people use instead of CagriSema

Weight loss with an approved product

  • Semaglutide
  • Tirzepatide

Targeting amylin (a fullness hormone) alone

  • Cagrilintide

Your questions

CagriSema FAQ

Is CagriSema approved?

No — not anywhere. Novo Nordisk submitted it to the US FDA for weight management in December 2025, based on the REDEFINE 1 and 2 trials 9. For type 2 diabetes, the company says it will approach authorities to discuss the pathway 9.

Why do I see both 20.4% and 22.7% quoted for the weight loss?

Two ways of counting the same trial. 20.4% counts everyone randomised, whether or not they stayed on the drug (the treatment-policy estimand); 22.7% counts people while treated as intended (the trial-product estimand) 1. Both are real REDEFINE 1 numbers — one answers "what happens if it is prescribed", the other "what happens if you take it".

Is this the same as taking cagrilintide and semaglutide separately?

The phase 2 trial gave the two drugs as separate injections on the same day, co-escalated in matching steps 37. Phase 3 used a fixed-dose dual-chamber pen delivering both in one injection 1. No trial tested improvised combinations of separately sourced products — stacking the two components yourself is community practice, not the studied product (community-reported, not peer-reviewed).

How much better is it than semaglutide alone?

In REDEFINE 1, weight fell 20.4% on the combination against 14.9% on semaglutide 2.4 mg — 5.5 percentage points more 1. In type 2 diabetes, HbA1c (the 3-month blood sugar average) fell 1.91 percentage points against 1.75 on semaglutide 2.4 mg — a 0.16-point edge that was statistically significant (p=0.0035) 5. The stomach and gut cost was real but modest: 86.9% vs 81.2% had adverse events in that head-to-head 5.

What are the doses of the two drugs in CagriSema?

Equal doses of both, escalated together: 0.25, 0.5, 1.0, 1.7, then 2.4 mg of each drug, stepping up every 4 weeks to maintenance at week 16 17. REIMAGINE 2 also studied 1.0 mg each as its own maintenance dose in 595 people 5.

9 sources

References

Every numbered marker on this page points to one of these. Same sources, same numbering as the CagriSema research profile on Peptide Initiative.

  1. Coadministered Cagrilintide and Semaglutide in Adults with Overweight or Obesity (REDEFINE 1)Garvey WT, Blüher M, Osorto Contreras CK, et al. · 2025
  2. Cagrilintide-Semaglutide in Adults with Overweight or Obesity and Type 2 Diabetes (REDEFINE 2)Davies MJ, Bajaj HS, Broholm C, et al. · 2025
  3. Efficacy and safety of co-administered once-weekly cagrilintide 2.4 mg with once-weekly semaglutide 2.4 mg in type 2 diabetesFrias JP, Deenadayalan S, Erichsen L, et al. · 2023
  4. Safety, tolerability, pharmacokinetics, and pharmacodynamics of concomitant administration of multiple doses of cagrilintide with semaglutide 2.4 mgEnebo LB, Berthelsen KK, Kankam M, et al. · 2021
  5. Cagrilintide-semaglutide (CagriSema) versus semaglutide or cagrilintide in people with type 2 diabetes (REIMAGINE 2)Buse JB, Bajaj HS, Dalskov SM, et al. · 2026
  6. Cagrilintide: A Long-Acting Amylin Analog for the Treatment of ObesityD'Ascanio AM, Mullally JA, Frishman WH · 2024
  7. Novo Nordisk trial protocol NN9838-4862: co-administration of cagrilintide s.c. 2.4 mg and semaglutide s.c. 2.4 mg (posted on ClinicalTrials.gov, NCT04982575)Novo Nordisk A/S · 2021
  8. WEGOVY (semaglutide) injection — Prescribing InformationNovo Nordisk / U.S. FDA (DailyMed) · 2024
  9. Novo Nordisk company announcement: CagriSema regulatory submissionNovo Nordisk A/S (company announcement — not peer-reviewed) · 2025

Want the deep science?

Read the full CagriSema research profile

Every claim on this page traces back to the research database behind Peptide Initiative — studies, citations, clinical trial data, and the technical detail we deliberately left out here.

Open the research profile

More weight loss guides

This guide is education, not medical advice. CagriSema is a research compound that is not FDA-approved for human use. Talk to a clinician before taking anything.