Research

CagriSema vs Tirzepatide: Ahead at 5 mg, Not 15 mg

Creator: Julian Reyes, Health Writer
Published: 2026-09-22

Novo Nordisk's REIMAGINE 5 put its experimental combination ahead of tirzepatide 5 mg on weight loss in type 2 diabetes. Against full-dose tirzepatide, CagriSema has not come out ahead, and because it is not approved, for now it is available only in clinical trials.

Julian Reyes, Health Writer September 22, 2026 6 min read

The short version

On September 21, 2026, Novo Nordisk reported that CagriSema 1.0 mg/1.0 mg produced an estimated 12.4% weight loss at week 60 against 9.1% on tirzepatide 5 mg in REIMAGINE 5, a trial of 1,023 adults with type 2 diabetes; HbA1c fell 1.71 against 1.67 points.
Tirzepatide 5 mg is the second of six dose steps on the Mounjaro label, which runs up to 15 mg in adults, so REIMAGINE 5 compared two lower doses rather than the two drugs at full strength.
At full dose, CagriSema has not come out ahead: 15.2% weight loss against 15.8% for tirzepatide 15 mg in REIMAGINE 4, where it also fell short on blood sugar, and 23.0% against 25.5% in REDEFINE 4.
As of September 22, 2026, the day this article was written, the REIMAGINE 5 results were a company press release from an open-label trial, not a peer-reviewed paper.
CagriSema is investigational: there is no FDA-approved CagriSema product, and Novo expects an FDA decision on its weight-management application in the fourth quarter of 2026.
Tirzepatide and semaglutide are what a licensed provider can consider today. Through Promise both are compounded medications, which is different from an FDA-approved product: the formulations offered here are not FDA-approved.

The newest CagriSema vs tirzepatide result is a real one, with a large asterisk. On September 21, 2026, Novo Nordisk said its experimental weekly shot, CagriSema, led to an estimated 12.4% weight loss at week 60 in adults with type 2 diabetes, against 9.1% on tirzepatide, in a trial called REIMAGINE 5. The asterisk is the dose: tirzepatide was given at 5 mg, a third of its 15 mg maximum. In the two trials that put CagriSema against full-dose tirzepatide, CagriSema has not come out ahead. And it still is not something anyone can be prescribed.

As of September 22, 2026, the day this article was written, the REIMAGINE 5 numbers exist only as a company press release — a topline summary, not a peer-reviewed paper — and the trial's registry record lists no posted results.

REIMAGINE 5 results: what Novo announced

CagriSema is one weekly injection that combines two drugs. One is semaglutide, the medicine in Ozempic and Wegovy. The other is cagrilintide, a long-acting copy of amylin, a hormone released alongside insulin that helps tell the brain a meal is over. What is cagrilintide covers that half in full.

REIMAGINE 5 enrolled 1,023 adults with type 2 diabetes and a BMI of 30 or more whose blood sugar was not controlled on metformin, an SGLT2 inhibitor (a class of diabetes tablets), or both, according to its ClinicalTrials.gov record, NCT06534411. People were randomly assigned to CagriSema 1.0 mg/1.0 mg or tirzepatide 5 mg. The trial was open-label, meaning everyone knew which drug they were taking.

Novo's release reported two main results at week 60:

Week 60	CagriSema 1.0 mg/1.0 mg	Tirzepatide 5 mg	Novo's verdict
Average weight change	−12.4%	−9.1%	Superior
Average HbA1c drop	1.71 points	1.67 points	Non-inferior

HbA1c is a blood test that reflects roughly three months of blood sugar. Non-inferior means not meaningfully worse, by a margin set before the trial began. On blood sugar, the two landed close to even.

Both numbers use what Novo calls the efficacy estimand: an estimate of what would have happened if everyone had stayed on treatment as planned. Counting everyone, including people who stopped, usually gives smaller figures, and the release did not include them. On safety it said only that CagriSema was well tolerated overall, with no rates.

The same release reported REDEFINE 9, in adults with overweight or obesity: 21.0% average weight loss at week 68 on CagriSema 1.0 mg/1.0 mg, against 2.0% on placebo, again on the efficacy estimand.

Why the 5 mg dose changes the reading

The Mounjaro label, revised in August 2026, starts tirzepatide at 2.5 mg a week and raises it in 2.5 mg steps if more blood-sugar control is needed, up to 15 mg in adults. So 5 mg is the second of six steps.

Dose matters for tirzepatide. In SURPASS-2, a 40-week trial of 1,879 adults with type 2 diabetes, HbA1c fell 2.01 points at 5 mg and 2.30 points at 15 mg, and tirzepatide's weight advantage over semaglutide 1 mg grew from 1.9 kg at the lowest dose to 5.5 kg at the highest (Frías et al., NEJM 2021). SURMOUNT-2 results shows what the 10 mg and 15 mg doses did for weight in adults with diabetes.

To be fair to Novo, CagriSema was at a lower dose too: 1.0 mg of each drug, against the 2.4 mg of each used in most of its trials. Its release points out that not every patient receives or stays on the highest available dose, which is true in everyday care. That makes REIMAGINE 5 a fair test of two lower doses. It is not a test of which medicine is stronger.

CagriSema vs tirzepatide at full dose

Two earlier head-to-heads used tirzepatide 15 mg. Here they are beside the new one, as Novo reported them:

Trial	Who	Doses	CagriSema	Tirzepatide	Result
REIMAGINE 5, 60 weeks	Type 2 diabetes	1.0/1.0 mg vs 5 mg	−12.4% weight	−9.1% weight	Superior on weight
REIMAGINE 4, 68 weeks	Type 2 diabetes	2.4/2.4 mg vs 15 mg	−15.2% weight, HbA1c −1.9	−15.8% weight, HbA1c −2.2	Non-inferior on weight, not on HbA1c
REDEFINE 4, 84 weeks	809 adults with obesity	2.4/2.4 mg vs 15 mg	−23.0% weight	−25.5% weight	Missed its non-inferiority goal

REIMAGINE 4 comes from Novo's half-year report of August 4, 2026. REDEFINE 4 comes from its February 23, 2026 announcement, where counting everyone regardless of whether they kept taking treatment gave 20.2% versus 23.6%. All three were open-label, and none has appeared in a journal yet.

Put together: at lower doses, CagriSema lost more weight. At full doses, tirzepatide's numbers were higher in both trials, and on blood sugar CagriSema missed the bar Novo set.

What it means if you take tirzepatide or semaglutide

Very little changes. REIMAGINE 5 does not suggest tirzepatide works less well than its own trials showed. It says a lower dose of it lost less weight than a new combination did. Dose decisions stay where they were, with a prescriber weighing response and side effects.

One of CagriSema's two ingredients is semaglutide, a molecule a provider can already prescribe.

What the CagriSema type 2 diabetes trials show

None of the tirzepatide head-to-heads is published yet. The peer-reviewed CagriSema trials compared it with semaglutide alone or with placebo, and they suggest the amylin half adds something.

In REIMAGINE 2, published online in June 2026, 2,713 adults with type 2 diabetes were randomized, and CagriSema 2.4 mg/2.4 mg lowered HbA1c by 1.91 points at 68 weeks against 1.75 on semaglutide 2.4 mg alone (Buse et al., Lancet Diabetes Endocrinol 2026). In REDEFINE 2, adults with type 2 diabetes and overweight or obesity lost an average of 13.7% over 68 weeks on CagriSema against 3.4% on placebo, and gut side effects were reported by 72.5% against 34.4%, most of them mild or moderate and short-lived (Davies et al., NEJM 2025).

What the result does not mean

It does not mean CagriSema is available. Novo's own release calls it investigational. The application the FDA is reviewing, filed in December 2025, is for weight management, and Novo expects a decision in the fourth quarter of 2026. REIMAGINE 5 is a diabetes trial.

It does not mean CagriSema beats tirzepatide in general. So far, the full-dose trials say otherwise.

And it does not mean anyone can get it early. Vials sold online under the cagrilintide name are not the trial medicine. They come with no prescriber, no pharmacy of record and nobody to call if a batch is wrong.

What a provider can weigh today

Mounjaro and Zepbound are the branded tirzepatide products; Ozempic and Wegovy are the branded semaglutide ones. Through Promise, tirzepatide and semaglutide are dispensed as compounded medications, which is different from an FDA-approved product: the formulations offered here are not FDA-approved.

A licensed provider may still prescribe a compounded formulation — that decision is between you and your doctor. At Promise, a licensed provider reviews every request, and not everyone qualifies. If you are weighing the two that can be prescribed today, tirzepatide vs semaglutide sets out their own head-to-head trials.

What to watch next

The FDA's decision on CagriSema for weight management is the big one, expected in the fourth quarter of 2026.

Then the full REIMAGINE 4 and 5 data. Until they are presented or published, the side-effect rates, the dropouts and the count-everyone numbers are not public.

Further out, Novo said in February that REDEFINE 11, an 80-week trial of CagriSema 2.4 mg/2.4 mg, would report in the first half of 2027, and its August report put a higher-dose CagriSema trial's readout in the first half of 2028.

And Novo is not the only company pairing an amylin drug with a GLP-1-type medicine. Eli Lilly's own amylin candidate, eloralintide, has been tested alongside tirzepatide.

Common questions

Is CagriSema better than tirzepatide?

Not across the board. In REIMAGINE 5, CagriSema 1.0 mg/1.0 mg led to more weight loss than tirzepatide 5 mg, 12.4% against 9.1% at week 60, with blood-sugar results close to even. Against tirzepatide 15 mg, CagriSema has not come out ahead: 15.2% against 15.8% in REIMAGINE 4 and 23.0% against 25.5% in REDEFINE 4. All three were open-label trials reported by Novo Nordisk.

What were the REIMAGINE 5 results?

Novo Nordisk announced on September 21, 2026 that CagriSema 1.0 mg/1.0 mg produced an estimated 12.4% average weight loss at week 60, against 9.1% with tirzepatide 5 mg, in 1,023 adults with type 2 diabetes not controlled on metformin, an SGLT2 inhibitor or both. HbA1c fell 1.71 points against 1.67, which Novo called non-inferior. The release gave no side-effect rates.

Why did REIMAGINE 5 use tirzepatide 5 mg?

The trial compared lower doses of both drugs: 1.0 mg of each CagriSema component against tirzepatide 5 mg. Novo's release notes that not all patients receive or stay on the highest available dose of current treatments. That is a fair question to study, but it is a different question from which medicine is stronger, because the Mounjaro label runs up to 15 mg in adults.

Is CagriSema FDA-approved?

No. There is no FDA-approved CagriSema product in the United States, and Novo Nordisk's own September 21, 2026 release describes it as investigational. Outside clinical trials it is not available by prescription. Vials sold online under the cagrilintide or CagriSema name are not the trial medicine and come with no prescriber and no pharmacy of record.

When will CagriSema be approved?

No date has been set. Novo Nordisk filed CagriSema with the FDA for weight management in December 2025, based on the obesity trials REDEFINE 1 and REDEFINE 2, and its September 21, 2026 release says a decision is expected in the fourth quarter of 2026. The agency could agree, decline, or ask for more data, so nothing is certain until it acts.

Can I get CagriSema through Promise?

No. Promise does not offer CagriSema or cagrilintide, because there is no approved product to prescribe. What a licensed provider can consider today is tirzepatide or semaglutide. Through Promise both are dispensed as compounded medications, which is different from an FDA-approved product: the formulations offered here are not FDA-approved. The provider reviews your history and decides.