CagriSema REIMAGINE 5 vs GLP-2T: Phase 3 Head-to-Head Results

Novo Nordisk's CagriSema 1.0 mg/1.0 mg was superior to GLP-2T 5 mg for weight loss in the Phase 3 REIMAGINE 5 trial, achieving an estimated average weight loss of 12.4% versus 9.1% at week 60 in adults with type 2 diabetes, with non-inferior HbA1c reduction (1.71% vs 1.67%). The company also reported that CagriSema 1.0 mg/1.0 mg produced 21.0% weight loss versus 2.0% for placebo in the Phase 3 REDEFINE 9 obesity trial. (Novo Nordisk A/S via GlobeNewswire; Novo Nordisk Canada via CNW)

These topline results were announced at Novo's Capital Markets Day on September 21, 2026. They represent a direct Phase 3 superiority readout of an amylin/GLP-1 combination against a GLP-1/GIP dual agonist — a comparison type the research community has been watching for. FDA and Health Canada decisions on the already-filed weight-management application are expected in Q4 2026, per the company. (Novo Nordisk Canada via CNW)

The headline is significant but bounded. GLP-2T was tested at its 5 mg dose, not the 15 mg maximum used in obesity trials. Novo framed the result as evidence for dose flexibility in individualized care, and that framing is consistent with the data. What the data do not establish is that CagriSema at any tested dose matches or beats GLP-2T at its highest dose.

REIMAGINE 5 primary endpoints and secondary endpoints

Novo defined two dual primary endpoints for REIMAGINE 5, both measured from baseline (week 0) to the end of treatment at week 60: change in HbA1c and relative change in body weight. Novo's topline release reports both. CagriSema 1.0 mg/1.0 mg was superior to GLP-2T 5 mg on weight (12.4% versus 9.1%) and non-inferior on HbA1c (reductions of 1.71% and 1.67%). The registry gives the units as percentage points for HbA1c and percent for body weight, and the weight figures are based on the efficacy estimand. (Novo Nordisk A/S via GlobeNewswire; ClinicalTrials.gov NCT06534411)

Novo's release names only the primary endpoints and reports no secondary results. The registry record, which Novo last updated on October 19, 2026 and which we checked on November 6, 2026, lists these secondary endpoints, each from baseline to week 60 unless noted:

• Glycaemic control: change in HbA1c (the registry repeats it as a secondary measure), change in fasting plasma glucose, and the number of participants reaching HbA1c below 7.0% (53 mmol/mol) and at or below 6.5% (48 mmol/mol) at week 60.
• Weight: the number of participants achieving at least 5%, 10%, 15% and 20% weight reduction.
• Cardiometabolic measures: change in systolic and diastolic blood pressure and waist circumference, plus ratio-to-baseline total, HDL, LDL, VLDL and non-HDL cholesterol and triglycerides.
• Patient-reported outcomes: SF-36v2 physical component, mental component and vitality scores, and the IWQOL-Lite-CT physical function and total scores.
• Safety, through week 66: the number of treatment-emergent adverse events and of level 2 and level 3 hypoglycaemic episodes.

Topline values for these secondary endpoints have not been released. Treat any number you see for them as unpublished until the full results appear.

REIMAGINE 5 population: who was enrolled, sample size, duration and doses

REIMAGINE 5 (NCT06534411, Novo study ID NN9388-7741) enrolled adults with type 2 diabetes who also had a body mass index of 30 or higher. The registry, which Novo maintains, records the design as follows:

The comparator was a single fixed dose, not GLP-2T's full dose range, which is the point of the dose-gap section below. Because the trial was open-label, participants and investigators knew which drug was given.

Did REIMAGINE 5 enroll adults with overweight or obesity?

Partly. Everyone enrolled had type 2 diabetes, and the registered eligibility criteria require a BMI of at least 30 kg/m² at screening, which is the obesity range. Adults with overweight but a BMI below 30 were not eligible under those criteria, and the trial did not enroll adults without diabetes. Novo's topline release describes the population only as adults with type 2 diabetes inadequately controlled on metformin, an SGLT2 inhibitor or both, so the BMI threshold comes from the registry, not the release. The overweight-or-obesity population in Novo's announcement belongs to REDEFINE 9, which compared CagriSema with placebo. The weight-management filing described below rests on the REDEFINE program, not on REIMAGINE 5.

The headline numbers

In REIMAGINE 5, CagriSema 1.0 mg/1.0 mg met both dual primary endpoints measured from baseline to week 60: superiority on relative change in body weight and non-inferiority on HbA1c reduction. The trial enrolled adults with type 2 diabetes inadequately controlled on metformin, an SGLT2 inhibitor, or both. CagriSema was superior to GLP-2T 5 mg for weight loss at 12.4% versus 9.1%, and confirmed non-inferior HbA1c reduction at 1.71% versus 1.67%. (Novo Nordisk A/S via GlobeNewswire)

In REDEFINE 9, CagriSema 1.0 mg/1.0 mg delivered 21.0% weight loss versus 2.0% for placebo at week 68 in adults with overweight or obesity, meeting the primary superiority endpoint. The company also reported improvements across prespecified supportive endpoints, including systolic blood pressure, waist-to-height ratio, and fasting lipid profile, though numerical values for those endpoints were not disclosed in the topline release. (Novo Nordisk Canada via CNW)

Both trials showed CagriSema to be well tolerated overall, with a safety profile consistent with previous studies, according to Novo. The weight-loss figures are based on the efficacy estimand, meaning they reflect modeled treatment effect under assigned therapy rather than only observed completers — a caveat worth noting until full results are published and peer review is possible. (AllSci)

The dose gap: GLP-2T 5 mg is not GLP-2T 15 mg

This is the caveat that matters most for anyone interpreting the headline. GLP-2T's approved dosing for weight management escalates to 15 mg, and the pivotal REDEFINE 4 obesity head-to-head compared CagriSema 2.4 mg/2.4 mg directly against GLP-2T 15 mg. In that trial, per AllSci's reporting of prior data, CagriSema failed to demonstrate non-inferiority, achieving 23.0% weight loss versus 25.5% for GLP-2T 15 mg. AllSci also notes that in REIMAGINE 4 (disclosed on Novo's Q2 2026 earnings call), CagriSema 2.4 mg/2.4 mg was non-inferior to GLP-2T 15 mg on weight loss but failed the HbA1c non-inferiority co-primary endpoint. (AllSci)

The table below places the new result in that context. Note that the REIMAGINE 4 and REDEFINE 4 rows rely on secondary trade reporting and prior company disclosures, not the new release:

The REIMAGINE 5 result is therefore a distinct competitive scenario from the maximum-dose comparisons. It is most relevant to patients who do not escalate to or tolerate maximum doses of current therapies, which Novo itself emphasized in its release commentary. It is not evidence that CagriSema matches or exceeds GLP-2T at equivalent maximum exposure.

How cagrilintide works: amylin biology in brief

Per the company's release and AllSci's description, cagrilintide is a long-acting amylin analogue with activity at both amylin and calcitonin receptors. GLP-1S acts on GLP-1 receptors. The combination targets complementary pathways involved in appetite regulation and energy intake, which is the stated rationale for the fixed-dose pairing. (Novo Nordisk A/S via GlobeNewswire; AllSci)

Novo's chief scientific officer Martin Holst Lange described the combination as demonstrating "the strong potency" of pairing GLP-1S with cagrilintide and said the findings "add to the growing evidence for amylin biology." The company also stated that treatment decisions in obesity and type 2 diabetes are often individualized, and that not all patients receive or remain on the highest available dose of current therapies.

Note that the mechanistic framing above is Novo's own characterization of the compound; the topline release does not include peer-reviewed mechanistic data, and the topline figures have not yet been peer-reviewed.

Trial program map: REDEFINE versus REIMAGINE

Novo runs two parallel Phase 3 programs for CagriSema:

• REDEFINE evaluates CagriSema in adults with overweight or obesity, as an adjunct to a reduced-calorie diet and increased physical activity. The NDA filed with the FDA in December 2025 for weight management is supported by REDEFINE 1 and REDEFINE 2 data, per AllSci's reporting.
• REIMAGINE evaluates CagriSema in adults with type 2 diabetes inadequately controlled on metformin, an SGLT2 inhibitor, or both. No NDA has been submitted for the T2D indication. Novo said it would discuss the regulatory pathway for T2D with authorities following the broader REIMAGINE program results. (AllSci)

The REIMAGINE 5 result is scientifically informative but not attached to a current regulatory filing. The weight-management filing is the one relevant to the Q4 2026 decision timeline. The REIMAGINE 5 trial design and endpoints are documented in its public registry record (ClinicalTrials.gov NCT06534411).

Regulatory timeline

Novo filed a New Drug Application with the FDA and a New Drug Submission with Health Canada in December 2025 for CagriSema for weight management. Decisions from both agencies are expected in Q4 2026, according to the company. (Novo Nordisk Canada via CNW)

This means an approval decision is likely only weeks away, which is why readers searching "CagriSema approval" or "CagriSema vs Zepbound" will need a citable facts page now rather than after the fact.

This article is for general informational purposes only and is not medical advice. Talk to a licensed clinician about personal medical decisions.

What this does and doesn't prove

The REIMAGINE 5 result is, per available reporting, the first Phase 3 head-to-head superiority readout of an amylin/GLP-1 combination against a GLP-1/GIP agonist, and that is genuinely notable. It also adds a lower-dose data point for CagriSema that supports the case for dose flexibility.

What it does not prove: that CagriSema matches or beats GLP-2T at equivalent maximum doses, that the T2D indication will be approved, or that the 21.0% placebo-controlled result at the 1.0/1.0 mg dose will translate into a different market position than what REDEFINE 1 already established at 22.7% with the 2.4/2.4 mg dose. The competitive picture against Eli Lilly's Zepbound remains shaped by the earlier maximum-dose non-inferiority failure, as reported by AllSci. (AllSci)

In short: a real, well-bounded win for Novo in a lower-dose scenario — and a reminder to read every head-to-head table for the dose column before drawing class-level conclusions.

Frequently asked questions

What were the primary endpoints in REIMAGINE 5?

Novo registered two dual primary endpoints, both measured from baseline to week 60: change in HbA1c and relative change in body weight. Novo's topline release says CagriSema 1.0 mg/1.0 mg was superior to GLP-2T 5 mg on weight loss (12.4% versus 9.1%, efficacy estimand) and non-inferior on HbA1c (1.71% versus 1.67%). Secondary endpoints are registered but no secondary results have been released.

Was REIMAGINE 5 conducted in people with overweight or obesity?

Partly. REIMAGINE 5 enrolled adults with type 2 diabetes, and its ClinicalTrials.gov record requires a BMI of at least 30 kg/m² at screening, so participants had obesity-range BMI alongside diabetes. Adults with overweight but a BMI below 30 were not eligible, and people without diabetes were not enrolled. Novo's release describes only the diabetes criterion; the overweight-or-obesity population in its announcement belongs to REDEFINE 9.

How many people were in REIMAGINE 5, and how long did it last?

The registry lists 1,023 enrolled participants in a randomized, open-label Phase 3 trial. CagriSema 1.0 mg/1.0 mg was escalated over 8 weeks and maintained for 52 weeks, and GLP-2T 5 mg was escalated over 4 weeks and maintained for up to 56 weeks. The primary timepoint was week 60 and the study period ran to week 66.

Did CagriSema beat the maximum dose of GLP-2T?

No. REIMAGINE 5 tested GLP-2T at 5 mg, not the 15 mg maximum dose used in obesity trials. In the earlier REDEFINE 4 head-to-head, CagriSema 2.4/2.4 mg did not demonstrate non-inferiority to GLP-2T 15 mg (23.0% vs 25.5% weight loss), per AllSci's reporting.

What is CagriSema?

CagriSema is a fixed-dose combination of cagrilintide (a long-acting amylin analogue with activity at amylin and calcitonin receptors) and GLP-1S (a GLP-1 receptor agonist), taken as a once-weekly subcutaneous injection. It is investigational and not yet approved for any indication.

When will CagriSema be approved?

Novo filed an NDA with the FDA and a New Drug Submission with Health Canada in December 2025 for weight management. Decisions from both agencies are expected in Q4 2026, according to the company.

Is CagriSema approved for type 2 diabetes?

No. The REIMAGINE 5 data support a potential T2D indication, but no NDA has been submitted for that use. Novo said it would discuss the regulatory pathway for T2D with authorities after reviewing the broader REIMAGINE program.

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

REDEFINE trials evaluate CagriSema in adults with overweight or obesity (adjunct to diet and exercise). REIMAGINE trials evaluate CagriSema in adults with type 2 diabetes inadequately controlled on background therapy.

Continue your research

• Survodutide Phase 3 SYNCHRONIZE: 16.6% Weight Loss, Visceral and Liver Fat Cuts, Not FDA Approved
• Mazdutide Phase 2 Results: 18.1% Weight Loss at 32 Weeks

Sources

• Novo Nordisk A/S via GlobeNewswire (Sept 21, 2026)
• Novo Nordisk Canada via CNW / newswire.ca (Sept 23, 2026)
• AllSci: Novo's CagriSema beats lower-dose GLP-2T in REIMAGINE 5 (Sept 22, 2026)
• ClinicalTrials.gov: REIMAGINE 5 record (NCT06534411), last updated October 19, 2026, checked November 6, 2026
• Life Sciences BC: Novo Nordisk Canada release (Sept 23, 2026)