By Patrick Wingrove and Maggie Fick

(Reuters) -As Denmark's Novo Nordisk shops for its next CEO to replace Lars Fruergaard Jorgensen, it should look across the Atlantic for a leader deeply entrenched in the United States, by far its largest market, analysts told Reuters.

Novo, which manufactures the popular weight-loss drug Wegovy, said on Friday its current CEO will step down over concerns the company is losing its first-mover advantage in the highly competitive obesity drug market.

Financial analysts Reuters spoke with said an American may be better placed to deal with a Trump administration, which is rewriting the rules on pharmaceutical trade, manufacturing, regulation and drug pricing.

The Danish drugmaker became a world leader in the weight-loss drug market under Jorgensen's leadership, but in the U.S., the largest market for these drugs and where they are the most profitable, it has struggled against U.S. rival Eli Lilly.

Novo has gone head-to-head with the Indianapolis company for customers, signing contracts with insurers and launching a direct-to-consumer offering to match Lilly's obesity drug Zepbound. But Zepbound prescriptions surpassed those of Wegovy this year by more than 100,000 a week. Clinical trials show the drugs offer weight loss of 15% to 20%, though a Lilly-run head-to-head trial found Zepbound was more effective than Wegovy across five weight-loss targets.

The Danish drugmaker needs someone who understands the U.S. system better because they have "not competed to the same degree that Lilly has ... and it definitely feels like they are at a competitive disadvantage," said Barclays analyst Emily Field.

Novo, Denmark's largest drugmaker, has only had five CEOs in its 102-year history, all Danish, and naming a CEO from the U.S. would be a departure.

Jorgensen's predecessor, Lars Rebien Sorensen, who will now join the board in an observer role, had the top job from 2000 to 2016. Mads Ovlisen was in charge from 1981 to 2000.

Lilly's CEO has met many times with President Donald Trump while Novo said it has not.

Novo executives said on a call on Friday with investors they would look at both internal and external candidates and that the search is ongoing.

When asked whether an American CEO was needed, Jorgensen told Reuters: “I think we have a brilliant president of our U.S. organization who is an American and has been in the industry for long, and I think we are really well-covered there."

He was referring to the head of the U.S. business, Executive Vice President David Moore, who replaced Doug Langa last year.

Three of the largest European pharmaceutical companies - Roche, Bayer and Novartis - all have European CEOs, Berenberg analyst Kerry Holford pointed out, suggesting Novo should consider it.

The fact that no successor has been announced could show a preference for an external candidate this time, said Yuri Khodjamirian, chief investment officer at Tema ETFs.

Morningstar analyst Karen Andersen said that Novo traditionally chooses long-time insiders for the CEO role, but said of Novo: "I think it could be looking externally, given how dynamic the market is becoming on so many levels."

THE U.S. MARKET

Trump, who campaigned on a promise to boost domestic manufacturing, has been piling pressure on drugmakers since taking office to move medicine production to the U.S., threatening sector-specific tariffs on the industry.

The Trump administration singled out Novo's Wegovy and Lilly's Zepbound as targets in its push to lower prescription drug prices. The U.S. pays the most for drugs in the world, often nearly three times that of other developed nations, and Trump has said he wants to close that spread.

In the face of those challenges, analysts said, Lilly has benefited from the connections its CEO David Ricks has built with the Trump administration.

Ricks, who was made chair of industry lobbying group PhRMA in 2020, and CEOs of other major drugmakers like Pfizer - the current head of the group - have met with Trump several times since December. Former Lilly executive Alex Azar served as U.S. Secretary of Health and Human Services during Trump's first term.

Jorgensen, who after eight years in the role is one of the shortest-serving CEOs at Novo Nordisk, told Reuters on Friday that he has not met with Trump but has met with Trump administration officials.

"Dave Ricks knows how to meet this moment. He understands when to push and when to pull back," said BMO analyst Evan Seigerman, referring to the CEO's familiarity with U.S. politics.

(Reporting by Patrick Wingrove in New York and Maggie Fick in London; Additional reporting by Jacob Gronholt-Pedersen and Bhanvi Satija; Editing by Caroline Humer)