CagriSema and the Power of a Pairing: The REDEFINE Results

Combine a GLP-1 drug with an amylin analog, and most patients achieve a 20% weight loss—strong data — arriving in a suddenly crowded field.

Novo Nordisk’s answer to the triple agonist is a duet. CagriSema combines semaglutide with cagrilintide, a long-acting amylin analog, in a single weekly injection: two appetite pathways, one syringe. The phase 3 REDEFINE program, published in The New England Journal of Medicine and presented at the American Diabetes Association’s Scientific Sessions in June 2025, put the combination to the test.

What REDEFINE 1 showed.

REDEFINE 1 randomized 3,417 adults with obesity or overweight and a weight-related condition, but without diabetes, to CagriSema, to each component alone, or to placebo, across 68 weeks.

Among patients who adhered to treatment — the trial-product estimand — CagriSema produced 22.7% weight loss. That compared with 16.1% for semaglutide alone, 11.8% for cagrilintide alone, and 2.3% for placebo. Under the more conservative treatment-policy analysis, which counts everyone regardless of adherence, the figure was 20.4%. More than half of the participants lost at least a fifth of their body weight, and better than one in five lost 30% or more.

The secondary picture reinforced the headline. Waist circumference, blood pressure, and lipids improved, and lead investigator W. Timothy Garvey noted that by the end of the trial, most CagriSema-treated participants were no longer classified as obese.

The diabetes arm

REDEFINE 2, run in adults with type 2 diabetes, showed 13.7% weight loss against 3.4% on placebo at 68 weeks — a smaller effect, consistent with the pattern that people with diabetes tend to lose somewhat less on these drugs. A later study, REIMAGINE, presented at ADA in 2026, extended the combination’s edge over semaglutide in diabetes.

The number that shaped the narrative

Here is where trials meet expectations. CagriSema’s 22.7% is excellent by any historical standard — roughly on par with tirzepatide’s 15 mg dose in SURMOUNT-1. Yet Novo had once signaled 25%, and the miss dominated coverage. It landed harder still because retatrutide had just raised the ceiling to 28%.

The investigators offered useful nuance. Dosing in REDEFINE 1 allowed flexibility, so many participants did not stay at the maximum dose — a design closer to real-world practice, where clinicians titrate to tolerance. Read that way, 22.7% may understate what a patient held at full dose could achieve, while better reflecting what average use looks like.

The mechanism is worth understanding.

Why does adding amylin help? The authors argue the two molecules act on complementary appetite circuits in the brain — the hypothalamus, hindbrain, and septum among them — combining homeostatic and hedonic control of eating. Amylin and GLP-1 overlap but are not redundant, which is why the pairing beats either alone by a wide margin.

What it means

Novo submitted CagriSema to the FDA for weight management in December 2025. The evidence base is deep and peer-reviewed; the commercial challenge is that the neighbors grew taller between the trial’s design and its readout.

For patients, that competition is the good news. CagriSema, retatrutide, tirzepatide, and amycretin are pushing achievable weight loss into ranges that once required surgery — and giving clinicians more than one tool to match to the person in front of them.

Frequently asked questions

What is CagriSema? It is a once-weekly injection that combines two molecules: semaglutide, a GLP-1 receptor agonist, and cagrilintide, a long-acting amylin analog. The pairing targets two appetite pathways at once, which is why it outperforms either component alone.

Is CagriSema better than Wegovy? In REDEFINE 1, CagriSema produced about 22.7% weight loss among adherent patients versus 16.1% for semaglutide (the active ingredient in Wegovy) alone. So the combination beat semaglutide by a clear margin, though it fell short of the 25% figure Novo had once signaled.

When will CagriSema be approved? Novo Nordisk submitted CagriSema to the FDA for weight management in December 2025. A decision timeline depends on the agency’s review; approval had not been finalized as of mid-2026.

Sources

1. Garvey, W.T., Blüher, M., et al. “Coadministered Cagrilintide and Semaglutide in Adults with Overweight or Obesity” (REDEFINE 1). New England Journal of Medicine, 2025. DOI: 10.1056/NEJMoa2502081. ClinicalTrials.gov NCT05567796.
2. Davies, M.J., et al. “Cagrilintide–Semaglutide in Adults with Overweight or Obesity and Type 2 Diabetes” (REDEFINE 2). New England Journal of Medicine, 2025;393:648–659. DOI: 10.1056/NEJMoa2502082.
3. American Diabetes Association — 85th Scientific Sessions, ADA Meeting News, June 22, 2025 (Garvey presentation).
4. Novo Nordisk A/S — REDEFINE 1 press release, PR Newswire, June 22, 2025.
5. Pharmaceutical Executive — “Novo Nordisk’s CagriSema Falls Short of 25% Weight Loss Target,” 2025.