Novo Nordisk will test zenagamtide head-to-head against its own semaglutide in Korea

Novo Nordisk has won approval from South Korea's Ministry of Food and Drug Safety to run three late-stage trials of zenagamtide, a drug formerly known as amycretin that acts on both the GLP-1 and amylin receptors in a single molecule ^[1]. The clearances, granted on Aug. 12 and the following Friday, let the company begin enrolling Korean patients as part of a larger global program called AMBITION ^[1].

One of the three studies, called AMBITION 4, will directly compare a low dose of zenagamtide against semaglutide, the active ingredient in Ozempic and Wegovy, in 1,060 people with type 2 diabetes who are not controlled on standard pills ^[1]. Korea will contribute 60 patients to that trial ^[1]. Testing a new drug against a company's own marketed product, rather than a placebo, is a stronger signal than usual that Novo Nordisk expects zenagamtide to eventually replace, not just supplement, semaglutide.

The largest of the three studies, AMBIENCE, is a cardiovascular outcomes trial enrolling 8,500 people with established heart disease who are overweight or obese ^[1]. It will track deaths, heart attacks, strokes, and hospitalizations for heart failure, and is scheduled to run until December 2030, with Korea enrolling 250 patients ^[1]. A third trial, AMBITION 2, will test zenagamtide in 450 people with diabetes and chronic kidney disease, with 45 enrolled in Korea ^[1].

Novo Nordisk told investors on an Aug. 5 earnings call that it planned to begin the AMBITION program before the end of the year, and the Korean sites are expected to start enrolling in October ^[1]. Zenagamtide is built as a single engineered molecule that activates both the GLP-1 and amylin receptors, which sets it apart from Novo's other amylin-targeting drug, CagriSema, a fixed-dose combination of two separate peptides, cagrilintide and semaglutide ^[2]. Some industry materials describe zenagamtide as the company's planned follow-on to CagriSema, positioned for launch after 2027, though that timing has not been confirmed in regulatory filings ^[2].

Earlier weight-loss results for the molecule vary depending on the source and study stage. One industry summary cites weight loss of roughly 22% in a phase 1b/2 study lasting about 36 weeks, without specifying the patient population ^[2]. The specific figure of up to 14.6% weight loss at week 36 on a 40 mg weekly dose in people with type 2 diabetes, reportedly presented at the ADA 2026 meeting, could not be independently confirmed in the sources reviewed for this article. Readers should treat exact percentage claims for zenagamtide's weight-loss effect as unsettled until full study data are published.

Why it matters for patients

For people currently using semaglutide products like Ozempic, Wegovy, or Rybelsus, this news does not change anything about the medicine they are taking today. Zenagamtide is not approved anywhere and remains in mid- to late-stage testing ^[1]. The newly cleared trials are designed to generate evidence, including a direct comparison against semaglutide, that regulators would need before any approval decision ^[1].

The cardiovascular trial, AMBIENCE, matters because it is testing whether the drug can reduce heart attacks, strokes, and heart failure hospitalizations in people who already have heart disease, not just whether it helps with weight or blood sugar ^[1]. That kind of outcome data, if positive, could eventually support broader use, but the trial does not finish enrollment tracking until December 2030 ^[1].

Because Novo Nordisk is testing zenagamtide against its own semaglutide rather than a placebo, the company appears to be building a case that this newer drug could eventually replace semaglutide-based products in some patients. That does not mean current products are being withdrawn or are less safe; it means the company is preparing evidence for what it may position as a next-generation option.

What happens next

The Korean trial sites are expected to begin enrolling patients in October ^[1]. Novo Nordisk has said the broader AMBITION program will start globally before the end of 2026 ^[1]. The cardiovascular outcomes trial, AMBIENCE, is scheduled to continue collecting data through December 2030 ^[1]. Separately, Novo's related amylin-targeting drug, CagriSema, has a regulatory filing under review with a decision expected in late 2026, though that is a different molecule with its own trial results ^[2].