Amylin race: CagriSema in women, Lilly's Phase 3 filings

The next contest in obesity drugs is over amylin, a pancreatic hormone that signals fullness, and both market leaders moved this week. On October 20, Novo Nordisk presented new analyses of its combination drug CagriSema in women. A day earlier, on October 19, ClinicalTrials.gov posted the first two Phase 3 trials of Eli Lilly’s competing combination, which Lilly calls EloraTZP.

Both products pair an amylin drug with an existing incretin. CagriSema combines cagrilintide, a long-acting amylin analog, with semaglutide, the active ingredient in Wegovy. EloraTZP combines Lilly’s experimental amylin agonist eloralintide with tirzepatide, the active ingredient in Zepbound. Neither combination is approved anywhere in the United States.

What Novo reported

Novo’s data come from REDEFINE 1, a finished 68-week Phase 3 trial in 3,417 adults with obesity or overweight and without type 2 diabetes, about two-thirds of them women. Across all participants, CNBC noted, CagriSema produced average weight loss of 22.7% versus 2.3% on placebo.

At The Menopause Society’s annual meeting in San Diego, researchers led by Maria D. Hurtado Andrade of the Mayo Clinic presented two posters that looked only at the women. Among all 2,309 women, average weight loss at week 68 was 25.0% on CagriSema, 19.0% on semaglutide alone, 13.4% on cagrilintide alone and 3.0% on placebo. In a second analysis of 1,902 women sorted by menopause stage, average loss on CagriSema was 26.7% for premenopausal, 24.8% for perimenopausal and 23.1% for postmenopausal women, against 2.1%, 1.7% and 2.6% on placebo.

All of those figures use what Novo calls the efficacy estimand, which estimates results as if every participant had stayed on treatment. Real-world adherence is lower, so treatment-policy results, which count people who stopped, are typically smaller.

On safety, the press release repeats the full-trial numbers: 5.9% of CagriSema participants stopped because of adverse events versus 3.5% on placebo, and gastrointestinal side effects were reported by 79.6% versus 39.9%.

What is not known

The release is unusually direct about the limits. Menopause stage “was derived post hoc using age, medical history, and recorded symptoms and was not based on prospectively collected reproductive staging or biochemical confirmation.” The p values were not adjusted for multiple comparisons, and no formal test checked whether the drug works differently by sex or by stage. Novo calls the analyses “hypothesis generating.”

In plain terms, the women-only figure is a slice of a trial that was mostly women to begin with, so it is close to the overall result. The menopause split is a regrouping of the same data after the fact. Neither establishes that CagriSema works better in women or at any particular life stage. It is also not known how the women’s results look under the treatment-policy estimand, which the release does not report.

Novo filed a New Drug Application with FDA in December 2025, and says a decision is expected in Q4 2026.

What Lilly registered

Lilly’s two registry entries, both first submitted on October 12 and posted on October 19, describe the drug as LY900043, a coformulation of eloralintide and tirzepatide:

Trial	Population	Arms	Estimated enrollment	Primary endpoint
NCT07881432	Obesity without type 2 diabetes	Five EloraTZP dose levels, tirzepatide alone, eloralintide alone, placebo	2,115	Percent change in body weight at week 100
NCT07881458	Obesity or overweight with type 2 diabetes	EloraTZP versus tirzepatide	1,000	Percent change in body weight at week 100

Both are double-blind, listed as not yet recruiting, and give estimated primary completion in October 2029. The design matters: by testing the combination against tirzepatide alone, Lilly is setting out to show that adding amylin improves on its own best-selling drug, not only on placebo. Lilly’s September 15 release scheduled Phase 2 results for the combination for an EASD symposium on September 30. We did not find a Lilly announcement of the Phase 3 program; the registry entries are the first public record of these trials that we found.

Why it matters

For the GLP-1 market, the CagriSema decision due this quarter is the nearer event. If approved, it would be the first amylin-incretin combination on the market, years ahead of EloraTZP. For readers following the unregulated market, both programs are a reminder of how fast the approved pipeline is moving: retatrutide, another Lilly molecule still in trials, is already sold illegally online as a “research” product, which shows how quickly an experimental drug can reach that market.

What to watch

FDA’s decision on CagriSema; full publication of the REDEFINE 1 subgroup data; when Lilly’s trials open to enrollment; and whether Lilly publishes more Phase 2 detail on EloraTZP.