Novo Nordisk wins Korean approval for three phase 3 zenagamtide trials

Novo Nordisk has won South Korean approval to run three late-stage trials of zenagamtide, an experimental drug it previously called amycretin, including one that tests it directly against semaglutide, the molecule in Ozempic and Wegovy ^[1].

The Ministry of Food and Drug Safety cleared the three phase 3 studies in August, according to filings on the regulator's clinical trials database ^[1]. The trials belong to AMBITION, Novo's phase 3 program for zenagamtide in diabetes and heart disease ^[1]. On an Aug. 5 earnings call, the company said it would begin the AMBITION program before the end of the year, and the Korean trials are due to start in October ^[1].

Zenagamtide is a single molecule that acts on both the GLP-1 and amylin receptors, the article reports ^[1]. That design differs from CagriSema, another Novo Nordisk candidate aimed at the same two receptors but made by combining two separate peptides, cagrilintide and semaglutide, at a fixed ratio, according to a research page published by a peptide supplier ^[2]. Novo has described zenagamtide as the next major product in its obesity and diabetes business after semaglutide ^[1].

The three trials and their sizes

The largest study, AMBIENCE, is a cardiovascular outcomes trial in 8,500 patients who have established heart disease and are overweight or obese. It will track deaths, heart attacks, strokes and hospitalizations for heart failure, and it runs to December 2030. Korea will contribute 250 patients ^[1].

AMBITION 4, in 1,060 patients, pits a low dose of zenagamtide against semaglutide in people with type 2 diabetes that is not controlled on standard pills. Korea will enroll 60 of those patients ^[1].

AMBITION 2, in 450 patients, tests the drug in people with diabetes and chronic kidney disease. Korea will enroll 45 patients ^[1].

The Korean filings do not say how the two drugs will be dosed beyond describing the zenagamtide arm as a low dose, and no results from AMBITION 4 or AMBITION 2 have been reported ^[1].

What is not yet known

Nothing has been disclosed about how zenagamtide compares with semaglutide in people, how the two differ on side effects or tolerability, when the diabetes trials will read out, or whether Novo Nordisk plans to file zenagamtide for approval in the United States ^[1]. No US filing, price, or launch timing has been reported. The same research page also states that zenagamtide is being studied in a separate phase 3 program called AMAZE, that an oral version has been tested in phase 2, and that Novo Nordisk filed CagriSema for US approval in December 2025; those details come from that page and are not in the Korean regulatory report ^[2].

Why it matters for patients

Semaglutide is already on the market as Ozempic and Wegovy, and tirzepatide is sold as Mounjaro and Zepbound. A company testing its own experimental drug against its own marketed product, rather than against a placebo, is a way of asking whether the new drug is at least as good as the one many patients take now ^[1]. Until that comparison is run and reported, there is no evidence that zenagamtide works better, works the same, or causes fewer side effects than semaglutide.

The AMBITION 4 design focuses on people with type 2 diabetes who have not gotten their blood sugar under control with standard pills, a group that often considers adding an injectable medicine ^[1]. AMBIENCE is aimed at a different question: whether the drug reduces deaths, heart attacks, strokes and heart-failure hospitalizations in people who already have heart disease and are overweight or obese ^[1]. Those outcomes take years to measure, which is why that trial runs to December 2030.

Because these are trials in other countries, they do not change what is currently available or covered in the US. Any effect on US availability or insurance coverage would come later, and has not been announced ^[1][2].

What happens next

• October 2026: the three Korean trials are due to begin enrolling ^[1].
• Before the end of 2026: Novo Nordisk has said it will start the AMBITION program ^[1].
• December 2030: AMBIENCE, the 8,500-patient cardiovascular outcomes trial, is scheduled to finish ^[1].
• Readout dates for AMBITION 4 and AMBITION 2 have not been reported ^[1].