The campaign For Your SweetHeart features videos from Dr. Travis Stork (pictured), host of the show “The Doctors.”

Boehringer Ingelheim and Eli Lilly are in a unique position — they have to position their third-in-class diabetes medication Jardiance as a heart drug.

The two drugmakers — armed with an updated label that shows the drug cuts the risk of cardiovascular death in patients with type-2 diabetes and heart disease — will enter uncharted territory in bringing Jardiance into the cardiologist’s office.

Jardiance, which helps temper blood-sugar levels, is the first diabetes drug approved by the FDA to reduce the risk of cardiovascular death in these patients. Jardiance was the third SGLT2 inhibitor to arrive in the U.S. market in 2014, after Johnson & Johnson’s Invokana and AstraZeneca’s Farxiga, but analysts say this new indication is expected to serve as a material differentiator with the potential to take the roughly $120 million-a-year drug to $4 billion.

See also: Diabetes marketers turn to big data, gaming to improve outcomes

Jardiance’s new marketing push is three-pronged: it needs educate people on the link between diabetes and heart disease, spread awareness among cardiologists, and communicate its value to payers.

Graham Goodrich, VP, marketing of diabetes for Boehringer Ingelheim, is now charged with promoting a diabetes drug for a heart disease-related outcome — a challenge for which there is no playbook.

“We’ve gone from low differentiation to dramatic differentiation,” he said. “People have been myopic on just managing their A1c levels and their sugar [levels]. Managing their sugar is helpful but alone that does not reduce the risk of cardiovascular disease.”

The unmet need among this patient population is significant, Goodrich pointed out. Educating patients, providers, and the health system about the overlap between type-2 diabetes and cardiovascular disease is their first and most important initiative, he said.

See also: Following positive outcomes data, a new diabetes class is on the rise

People with diabetes are between two and four times more likely to develop cardiovascular disease than people who don’t, according to the World Heart Federation. The Centers for Disease Control and Prevention estimates that more than 29 million people in the U.S. have diabetes and that one in three people will develop the disease in their lifetime. More than half of U.S. adults with type-2 diabetes do not understand that they are at an increased risk for heart disease, Lilly and BI have found in their research.

Drugmakers usually target primary-care physicians and endocrinologists for diabetes drugs, but Jardiance’s updated label now makes cardiologists an attractive specialty, Goodrich said.

“Cardiology will be an important area for us,” he said. “Cardiologists do not tend to prescribe anti-diabetic medications — it’s not something they consider to be in their bailiwick. But after we showed them the data and asked them during market research: ‘Do you think it’s a cardiovascular or diabetes drug?’ the heart doctor will tell you it’s for cardiology. They want to be a part of the conversation.”

The drugmaker already begun stressing the connection between diabetes and heart disease with the launch of its campaign, For Your SweetHeart, on November 22. The unbranded campaign is designed to elucidate the link between diabetes and heart disease as well as emphasize the role of the caregivers in decision making.

“It’s another important element,” Goodrich pointed out, saying that the company sees caregivers, spouses, and partners who look after people with type-2 diabetes as a critical part of their audience.

See also: Two new therapies made by Sanofi and Novo Nordisk to compete in crowded diabetes market

BI has already dabbled in DTC for Jardiance with its spot “That’s Life,” which debuted in July. Goodrich said the company is not ruling out a branded DTC effort for this label expansion.

“The DTC efforts will take on multiple fronts — disease education is one of the most motivating elements — but you’ll see a campaign from us in the future that pulls through the broader indication that Jardiance has just received,” Goodrich said.

The drugmaker has already begun to communicate the new label with payers and health systems. Jardiance’s formulary status among some payers already reflects the new data, which was first released in September.  

“Just like patients aren’t aware of the overlapping burden between cardiovascular disease and type-2 diabetes, most integrated delivery networks aren’t fully aware either,” he said. “We want to encourage payers to evaluate these populations in an integrated fashion. Payers want distinct value, against that measure we believe Jardiance is going to be very compelling.”

See also: Diabetes R&D narrows in on glycemic control

Analysts also find the new data compelling, saying they expect Jardiance’s outcomes data to be aggressively marketed because it dramatically differentiates the drug among the rest of the SGLT2 class. The new indication could mean drug sales of $4 billion by 2025, according to Evercore ISI analyst John Scotti. That’s up from the $88.6 million it generated in the first nine months of 2016 in the U.S. Another analyst, Vamil Divan, from Credit Suisse, wrote that the approval “sets the stage for greater Jardiance uptake, especially with primary-care physicians.”

Correction: An earlier version of this article misstated Jardiance’s expected annual U.S. sales. The drug is on pace to generate about $118 million in U.S. sales in 2016.