CagriSema: What to Know About the Next-Generation Wegovy

In the REDEFINE 1 trial, published in the New England Journal of Medicine in June 2025, participants taking CagriSema lost 22.7% of their body weight over 68 weeks. That is roughly 40% more weight loss than semaglutide alone achieved in the same trial. The difference comes from a second hormone, amylin, which works through an entirely separate satiety pathway in the brain. CagriSema combines cagrilintide (a long-acting amylin analogue) with semaglutide (the same GLP-1 medication in Wegovy) into a single once-weekly injection. It is not yet approved anywhere, but the results are the strongest we have seen from a dual-hormone approach. Below: what the data shows, how the combination works, and what it means for patients in Singapore.

What is CagriSema and how does it work?

CagriSema is a fixed-dose combination of two medications in one once-weekly injection:

• Semaglutide 2.4 mg, the same GLP-1 receptor agonist used in Wegovy. It acts on the hypothalamus to reduce appetite and slow gastric emptying.
• Cagrilintide 2.4 mg, a long-acting analogue of amylin, a hormone naturally produced by the pancreas alongside insulin after meals.

The two medications target different parts of the brain. Semaglutide activates GLP-1 receptors in the hypothalamus, the region that regulates hunger and energy balance. Cagrilintide activates amylin and calcitonin receptors in the area postrema, a hindbrain region that signals fullness through a separate neural circuit.

The two pathways work together, and the result is more than additive. Because CagriSema activates both satiety circuits at once, it reduces appetite more effectively than either component on its own. In the REDEFINE 1 trial, cagrilintide alone achieved 11.8% weight loss, semaglutide alone achieved 16.1%, and the combination achieved 22.7%, exceeding what you would expect from adding the two effects together.

The injection uses a dual-chamber pen that delivers both medications in a single shot. Dosing follows a 16-week escalation from 0.6/0.6 mg up to the maintenance dose of 2.4/2.4 mg, similar to how current GLP-1 medications are gradually titrated to minimise side effects.

Clinical trial results

REDEFINE 1: obesity without diabetes

The REDEFINE 1 trial enrolled 3,417 adults with obesity but without type 2 diabetes and followed them for 68 weeks. The results were published in the NEJM in June 2025.

The on-treatment weight loss figures:

• CagriSema: 22.7%
• Semaglutide alone: 16.1%
• Cagrilintide alone: 11.8%
• Placebo: 2.3%

Using the intention-to-treat analysis (which includes all participants regardless of whether they completed the study), CagriSema still delivered 20.4% weight loss versus 14.9% for semaglutide alone.

The threshold data is worth looking at closely. Among CagriSema participants, 97.6% lost at least 5% of their body weight, 60.2% lost at least 20%, 40.4% lost at least 25%, and 23.1% lost 30% or more. By comparison, Wegovy alone typically helps around 32% of patients lose 20% or more (STEP 1 data).

One standout number: 50.7% of participants moved from an obesity-range BMI to a non-obesity BMI by the end of the trial. Fat mass dropped by 35.7%, compared to 5.7% with placebo.

Fewer than two-thirds of participants reached the highest dose of 2.4/2.4 mg, which means the full effect of CagriSema may not have been captured in these results.

REDEFINE 2: obesity with type 2 diabetes

The REDEFINE 2 trial focused on 1,206 adults who had both obesity and type 2 diabetes, a population where weight loss is typically harder to achieve. Over 68 weeks, CagriSema delivered 15.7% weight loss on-treatment (13.7% ITT), compared to 3.1-3.4% with placebo. Among participants, 89.7% lost at least 5% of their body weight.

These numbers matter because diabetes medications often work against weight loss, and the metabolic environment of type 2 diabetes makes the body more resistant to shedding fat.

REIMAGINE 2: diabetes focus with active comparator

The REIMAGINE 2 trial, announced in February 2026, enrolled 2,728 adults with type 2 diabetes and compared CagriSema directly against semaglutide. CagriSema achieved 14.2% weight loss and a 1.91 percentage point reduction in HbA1c, versus 10.2% weight loss and 1.76 percentage point HbA1c reduction with semaglutide alone. Among CagriSema participants, 43% lost at least 15% and 24% lost at least 20%.

How CagriSema compares to current medications

The table below puts CagriSema next to the medications currently available or in late-stage development:

A direct comparison between CagriSema and tirzepatide (Zepbound) is not yet possible from these numbers because the trials used different populations and protocols. Novo Nordisk is running REDEFINE 4, a head-to-head trial of CagriSema versus tirzepatide 15 mg in approximately 800 adults over 72-84 weeks, which will provide a definitive answer.

The 22.7% vs 25% context

When Novo Nordisk released the REDEFINE 1 results, the company's stock dropped roughly 20% in a single day. The reason: Novo had guided investors to expect around 25% weight loss, and 22.7% fell short of that internal target.

Clinically, the reaction was overblown. CagriSema delivered 6.6 percentage points more weight loss than semaglutide alone in the same trial, a 40% relative improvement. For a patient who would have lost 16 kg on Wegovy, that translates to roughly 23 kg on CagriSema instead. Novo has since launched REDEFINE 11, an extended-duration study designed to determine whether longer treatment pushes results beyond 25%.

Side effects and tolerability

CagriSema's side effect profile follows the pattern of GLP-1 medications but at higher rates because of the added amylin pathway.

In REDEFINE 1, gastrointestinal side effects occurred in 79.6% of CagriSema participants versus 39.9% on placebo. The most common:

• Nausea: 55%
• Constipation: 30.7%
• Vomiting: 26.1%

For comparison, nausea rates with Wegovy alone are typically in the 30-44% range (STEP trials). The higher rates with CagriSema are likely the result of two appetite-regulating hormones acting on the gut at the same time.

Most side effects were rated as mild to moderate and tended to occur during the dose escalation phase. Discontinuation rates due to adverse events were 5.9-6.0% for CagriSema versus 3.5-3.7% for placebo, so most participants tolerated the medication well enough to continue.

The dose escalation numbers are also relevant here. Fewer than two-thirds of participants reached the maximum 2.4/2.4 mg dose during the trial period, which suggests a sizeable proportion needed a slower titration. Doctors see the same pattern with existing GLP-1 medications: some patients do best at a lower maintenance dose rather than pushing to the maximum.

If you are currently managing side effects on semaglutide or other GLP-1 treatments, CagriSema would likely involve a similar adjustment period.

When will CagriSema be available?

Novo Nordisk filed its New Drug Application (NDA) with the US Food and Drug Administration on 18 December 2025. The FDA typically takes 10-12 months to review, which places a potential approval in late 2026 or early 2027.

For Singapore, the Health Sciences Authority (HSA) conducts its own regulatory review, which generally follows FDA approval by 12-18 months. A realistic timeline for CagriSema availability in Singapore is 2027-2028 at the earliest.

Several ongoing trials will add to the evidence:

• REDEFINE 3: cardiovascular outcomes trial with approximately 7,000 participants
• REDEFINE 4: head-to-head comparison against tirzepatide 15 mg (approximately 800 participants, 72-84 weeks)
• REDEFINE 11: extended-duration study, initiated June 2025, aiming to determine whether longer treatment delivers more than 25% weight loss

What is available now in Singapore

CagriSema is still in the regulatory pipeline. In the meantime, several GLP-1 options are already available and prescribed through telehealth clinics like Trimly:

• Semaglutide (the same GLP-1 backbone used in CagriSema), available as Wegovy (injectable) and Ozempic (injectable, prescribed off-label for weight management)
• Oral semaglutide (Rybelsus), for patients who prefer a daily tablet over injections
• Tirzepatide (Mounjaro/Zepbound), a dual GLP-1/GIP receptor agonist

These medications deliver 14.9-22.5% weight loss depending on the specific treatment and dosage. Your doctor can help determine which option fits your health profile.

What this means for patients currently on Wegovy or semaglutide

If you are already taking semaglutide for weight loss, CagriSema would be a logical next step when it becomes available. The combination uses the same semaglutide backbone you are already on, with cagrilintide added to work through the amylin pathway.

This matters most for patients who have plateaued on semaglutide. Weight loss plateaus often occur because the body adapts to a single hormonal signal over time. Adding a second mechanism through amylin receptors in the hindbrain may help push past that plateau by targeting appetite from a different angle.

The REDEFINE 1 data supports this: the 6.6 percentage point improvement over semaglutide alone came specifically from the amylin component. For someone who has already lost 12-15% on Wegovy and stalled, that additional pathway could help move the needle again.

In the meantime, there is plenty you can do to maximise results on your current treatment. Our doctors at Trimly work with patients on dose optimisation, nutrition strategies, and lifestyle adjustments that support long-term weight management, whatever medication you are on.

Frequently asked questions about CagriSema

Is CagriSema available in Singapore?

No. CagriSema is not yet approved anywhere in the world. Novo Nordisk filed for FDA approval in December 2025, with a decision expected in late 2026 or early 2027. HSA approval for Singapore would likely follow in 2027-2028 at the earliest.

Is CagriSema better than Wegovy?

In the REDEFINE 1 trial, CagriSema achieved 22.7% weight loss compared to 16.1% for semaglutide (the active ingredient in Wegovy) over the same 68-week period. That is a 40% relative improvement. So yes, the clinical data indicates CagriSema is more effective for weight loss.

How does CagriSema compare to Zepbound (tirzepatide)?

Cross-trial comparisons are imperfect, but CagriSema's 22.7% and tirzepatide's 20.9-22.5% are in a similar range. The REDEFINE 4 trial is a direct head-to-head comparison that will provide a definitive answer. Results are expected in 2027.

Is CagriSema two injections?

No. It is a single once-weekly injection delivered through a dual-chamber pen that combines both medications. You do not need to inject twice.

Will CagriSema replace Wegovy?

Probably not as a direct replacement. CagriSema is more likely to be positioned as a next step up for patients who need more weight loss than semaglutide alone provides. Wegovy will likely remain a first-line option, with CagriSema available for those who plateau or need greater results.

What is amylin?

Amylin is a hormone produced by the same pancreatic beta cells that make insulin. It is released after meals and signals fullness through the area postrema in the hindbrain. This is a different satiety pathway from GLP-1, which works through the hypothalamus. Cagrilintide is a long-acting synthetic version of amylin that lasts long enough for once-weekly dosing.

Takeaways on CagriSema

CagriSema is the first dual-hormone weight loss injection to produce strong phase 3 data. The combination of semaglutide and cagrilintide produced roughly 40% more weight loss than semaglutide alone by targeting two separate appetite pathways in the brain.

The headline results from REDEFINE 1:

• 22.7% average weight loss at 68 weeks
• 60.2% of participants lost 20% or more
• 50.7% moved from obesity to non-obesity BMI
• Fat mass reduced by 35.7%

Side effects are higher than with Wegovy alone, particularly nausea (55% vs roughly 30-44%), and not everyone will tolerate the maximum dose. These are trade-offs your doctor will weigh against the benefits.

CagriSema is not available yet. FDA approval may come in late 2026, with Singapore availability likely in 2027-2028. In the meantime, the GLP-1 medications already available in Singapore, including semaglutide and tirzepatide, produce 15-22% weight loss and are accessible through telehealth clinics like Trimly.

If you are considering medical weight loss treatment or have plateaued on your current medication, a doctor can help you understand your options based on your individual health profile.

CagriSema is not yet approved by the Health Sciences Authority (HSA) in Singapore and is not available for prescription. The clinical trial results discussed in this article are preliminary and may not reflect the final safety and efficacy profile of the medication. This article is for educational purposes only.

Clinical trial results are based on controlled study conditions and may not reflect real-world outcomes. Weight loss results vary depending on individual factors including starting weight, adherence, diet, and exercise. The figures cited in this article come from specific trial populations and dosing regimens.

This article is for informational purposes only and does not constitute medical advice. Always consult your doctor before starting, stopping, or changing any medication. Individual results may vary. Trimly is a MOH-licensed telehealth clinic in Singapore (HCSA License R/25M0505/MDS/001/252).