The obesity drug revolution

The Food and Drug Administration in early March expanded the label for Novo Nordisk’s fast-selling weight loss drug Wegovy, following study results that proved the medicine can protect heart health. 

The agency approved use of Wegovy to reduce the risk of heart attacks, strokes or death in people with cardiovascular disease and who are either obese or overweight. The drug should be used alongside exercise and a reduced-calorie diet, the agency said. 

Wegovy, part of a popular class of medicines that control blood sugar and appetite, is already approved for use in treating obesity. The drug generated about $4.5 billion in sales in 2023 despite manufacturing issues that made it difficult for the company to meet surging demand. 

But Wegovy faces competition from Zepbound, a similar type of medicine developed by Eli Lilly that was cleared by the FDA last year for weight loss. Novo is also trying to stay ahead of a large group of competitors vying for a place treating obesity, a market Wall Street analysts believe could surpass $100 billion by the end of the decade. 

The FDA clearance issued March 8 is one step in that direction. It was based on the results of a large study, the results of which were published in The New England Journal of Medicine last year, showing that treatment with Wegovy reduced the risk of heart attack, stroke or cardiovascular death by 20% compared to a placebo. 

That result put Wegovy on the “list of established therapies that form the basis of our pharmacologic strategies for reducing the risk of cardiovascular disease” Amit Khera of the University of Texas Southwestern Medical Center and Tiffany M. Powell‑Wiley of the National Heart, Lung, and Blood Institute wrote in an NEJM editorial at the time. 

The findings separate Wegovy from Lilly’s rival medicines, at least for now. Results could come from a similar type of trial of Lilly’s Mounjaro, a version of Zepbound sold for Type 2 diabetes, later this year. A study of Zepbound could follow a few years later.

The results could also spur broader use of Wegovy, as such evidence can help sway insurers to cover treatment. Many payers have been hesitant to widely cover drugs like Wegovy, and Medicare is prohibited by law from doing so. (Later in March, the Centers for Medicare & Medicaid Services, which adminsters Medicare, said Wegovy treatment for cardiovascular reasons could be covered via Part D plans.)

“We definitely know these drugs work for weight loss,” Martha Gulati, director of preventive cardiology at Cedars-Sinai Medical Center, said in an interview last year. “In terms of accessing these medications, it’s quite the challenge. We do need to convince the insurers.”

Medicare will cover the costs of Novo Nordisk’s obesity drug Wegovy for some patients with a history of heart disease, a policy shift that could open up access to the in-demand weight loss medicine. 

The Centers for Medicare & Medicaid Services confirmed in late March that obesity drugs receiving Food and Drug Administration approval for an “additional medically accepted indication” may now be covered under so-called Part D plans. Those accepted uses include an approval to reduce the risk of heart problems or treat diabetes,  a spokesperson for the agency said. 

The new guidance currently only applies to Novo’s Wegovy, use of which the FDA expanded earlier this month based on clinical testing showing it can protect heart health. In a large study, treatment with Wegovy was associated with a 20% reduction in the risk of heart attacks, strokes or cardiovascular death compared to a placebo. 

Those findings separated Wegovy from rival medicines developed by Eli Lilly, which makes Zepbound for obesity and Mounjaro for diabetes, at least for now. Results from a similar trial of Mounjaro are expected later this year. A study of Zepbound could follow a few years later. 

The results were also seen as critical to spurring broader use of Wegovy, as such evidence can convince insurers to cover treatment. Wegoy has a list price of over $1,300 per month and payers have resisted covering the drug.

Medicare is prohibited by law from covering obesity medicines, meaning up until now, people with Part D plans had to cover the drug’s costs out of pocket. The CMS spokesperson said that Part D plans may consider using prior authorization for obesity drugs to “ensure they are being used for a medically accepted indication,” and not only weight loss. Those seeking coverage without a history of heart disease would need their plans to offer a supplemental benefit.

Even with those barriers, Wegovy has gotten off to a fast start. The drug generated about $4.5 billion in sales in 2023 despite manufacturing issues that made it difficult for the company to meet surging demand. Mounjaro, too, has quickly become a blockbuster, making obesity medicines one of the most lucrative opportunities in the history of the pharmaceutical industry. Analysts at investment bank Leerink Partners expect obesity drugs to generate $158 billion in yearly sales by 2032. 

Medicare’s shift in guidance could boost those estimates, broadening access to Wegovy and other weight loss drugs.  

Sponsored content

By OPEN Health

With industry experts predicting sales of glucagon-like peptide 1 (GLP-1) agonists to reach $50 billion by the decade’s end, now is the time for pharmaceutical companies to seize their share of this lucrative market. However, the road to unlocking the full potential of these drugs in treating chronic conditions is paved with obstacles, including patient adherence and payer reluctance. 

“The use of GLP-1 agonists is rapidly evolving. As new agents and dosing options come to market, pharma companies will need to be agile in their thinking and approach to maximize access and outcomes for patients,” says Annemarie Clegg, MD, Chief Medical Officer at OPEN Health

Patients

Adherence and persistence are often challenging for patients prescribed GLP-1 agonists. It is important to understand patients’ motivations, beliefs and perceptions regarding treatment with GLP-1 agonist therapy. “Integrating health psychology principles and developing a holistic intervention combining pharmacologic and behavioral science will be key in sustaining a long-term change in obesity,” says Sumira Riaz, CPsychol, Patient Engagement Lead at OPEN Health. “Building patient support which is sustainable versus short term will demonstrate longitudinal improved quality of life.” 

Healthcare professionals

As obesity rates continue to rise, prescriptions for GLP-1 agonists are exponentially increasing. However, healthcare professionals (HCPs) are inundated with information and data, making it difficult for them to distill and incorporate the latest strategies into practice. “Omnichannel-based approaches to HCP obesity education provide strategically focused, evidence-based and accessible content to integrated care teams, which can be used to inform treatment decisions, create patient-centric long-term management plans and ultimately impact overall patient health,” according to Dana Franznick, PharmD, Senior Director, Medical Strategy at OPEN Health.  

Payers

Uptake of GLP-1 agonists has the potential to revolutionize the treatment of obesity and diabetes, but could raise healthcare spending substantially, posing a problem for payers looking to control costs. Current access and reimbursement systems are not equipped to assess, reimburse and integrate indirect innovations, such as GLP-1 agonist therapy, with large budgetary and social impacts. Recent assessments in European countries, including Norway, Denmark and Germany, show there is a trend of payers refusing reimbursement for drugs that are generally considered lifestyle/cosmetic products. “It can be quite challenging to model the impact of weight changes on all the various conditions where obesity increases risk, especially when you add in the heterogeneity in the patient group and hence the baseline risk of these conditions,” says Elisabeth Fenwick, PhD, Chief Scientific Officer at OPEN Health. “Focusing on specific patient groups who are at increased risk of certain conditions will make the task more manageable and contained.”

Pharmaceutical companies

The surge in demand for GLP-1 agonists has led to supply issues, with off-label use limiting the availability of GLP-1 agonist therapy for eligible patients. Recent studies, such as the SELECT trial, have proven that in addition to providing weight loss in people with obesity, GLP-1 agonists can also lead to a reduction in the risk of cardiovascular events such as heart attack, stroke, or cardiovascular death. Safety concerns are emerging, such as whether GLP-1 agonists are associated with psychiatric issues and rare but serious gastrointestinal complications. Following reports of psychiatric issues, the US Food and Drug Administration concluded that there is no evidence of a causal link between these and the use of GLP-1 agonists, with the European Medicines Agency due to report on this in April 2024

Read the full whitepaper to learn about the major challenges faced by key stakeholders and how these challenges could be surmounted to forge a successful path forward. 

Amgen is a global pharmaceutical company worth more than $160 billion. Nine of its marketed medicines are blockbuster products by annual sales.

Yet, on a Feb. 6 conference call discussing Amgen’s fourth quarter earnings, all Wall Street analysts wanted to talk about was an experimental drug that only just cleared the first stage of human testing.

More than half of the questions asked by analysts were focused on AMG 133, a promising treatment for obesity that’s drawn attention as a potential competitor to in-demand weight loss medicines from Novo Nordisk and Eli Lilly. While Wall Street often overlooks the present to focus on the future, the intense interest in a drug years away from the market was noteworthy.

“Today was not a routine earnings call,” wrote Umer Raffat, an analyst from Evercore ISI, in a Feb. 6 note to clients.

Analysts’ scrutiny of AMG 133 is a byproduct of surging demand for so-called GLP-1 drugs like Novo’s Wegovy and Lilly’s Zepbound. Amgen’s drug also targets GLP-1, a gut hormone that regulates insulin secretion and is thought to play a role in signaling satiety, or fullness.

Estimates for size of the GLP-1 drug market have soared as clinical trial results have shown Wegovy and Zepbound can reduce body weight by 15% to 20%. More recent data has indicated GLP-1 drugs can reduce heart and kidney disease risk, as well as potentially treat a common liver illness. Some analysts expect total GLP-1 sales to reach as high as $100 billion.

That lofty potential has lured many companies into obesity drug research, including Pfizer, Roche, AstraZeneca and Boehringer Ingelheim. With AMG 133, Amgen is in the mix, too, and the drug’s advancement through testing has contributed to a run-up in the company’s stock.

On Feb. 5, results from a Phase 1 trial of the drug were published in Nature Metabolism, expanding on data previously shared by Amgen. They show that a high dose of AMG 133, given monthly, can reduce body weight by up to 15%, with weight loss sustained through several months.

But the paper also detailed caveats, including participant drop out rates in one of the study's arms, a high rate of gastrointestinal side effects and an uneven effect on levels of cholesterol and triglycerides.

Analysts pressed Amgen executives on these questions Feb. 6, probing what Jefferies’ Michael Yee called the “most scrutinized Phase 1 publication.” In particular, analysts were keen to assess how AMG 133 might stack up against either Wegovy or Zepbound, which are both once-weekly injections.

Jay Bradner, Amgen’s new head of research and development, pushed back against some of analysts’ concerns, such as AMG 133’s inconclusive effect on lipid measurements.

“I would just caution that this is a Phase I trial, the numbers are very small, that the duration of treatment is rather short,” Bradner said. “We take no concern whatsoever from those measurements on the study.”

Amgen executives also defended the design of AMG 133, which in addition to activating GLP-1 is designed to block another hormone receptor called GIP. That mechanism of action is opposite to Zepbound, which activates GIP as well as GLP-1.

Amgen has pointed to genetics data suggesting that blocking GIP could be helpful in delivering greater body weight reductions. “We feel very secure in our choice to inhibit that receptor,” said Amgen CEO Robert Bradway on Tuesday’s call.

Still, the conflicting approaches pose a unique test for Amgen to prove its design is better. (Wegovy doesn’t target GIP.)

“With Eli Lilly and Novo so far ahead, the burden will be with Amgen to differentiate,” wrote Mizuho analyst Salim Syed in a Feb. 6 note to clients.

Amgen will have a chance toward the end of this year, when it’s expecting to disclose results from a Phase 2 study of AMG 133. The company recently added a second part to this trial to test weight loss reductions beyond one year.

Before then, Amgen will report early trial data on another drug for obesity, AMG 786, that works in a different way than AMG 133.

For Wall Street, the question has become how much Amgen’s current value already reflects the potential for its obesity drugs to compete with Wegovy and Zepbound.

“Depending on who you talk to, AMG 133 makes up $50, $100, $320 of Amgen’s current valuation based on their Phase 1 data and the potential for this incretin targeting drug to be the better mouse trap vs. Lilly and Novo’s tirzepatide and semaglutide,” wrote Baird analyst Brian Skorney in a research note.

An experimental obesity drug from Boehringer Ingelheim and Zealand Pharma succeeded in a mid-stage liver disease study, the latest evidence new weight loss medicines could also help people with metabolic dysfunction-associated steatohepatitis, or MASH.

Summary results disclosed Feb. 26 showed that up to 83% of trial participants treated with the companies’ drug, survodutide, experienced a significant improvement in their disease without worsening liver scarring, compared to about 18% of those given placebo. The drug met its secondary study goals, notably demonstrating a benefit on liver scarring, the companies said.

In recent years, drugs known as incretins have become the industry’s most coveted products, proving able to treat diabetes, help people to lose weight and even protect heart health.

Clinical trial results like those from Boehringer and Zealand are now indicating incretins may play a role treating MASH, a disease estimated to affect millions of people and one of the leading causes of liver transplants.

MASH is caused by a toxic build-up of liver fat, and often develops alongside other metabolic diseases like diabetes. While it has long been a top drug target, it’s proven difficult for companies to crack. Several promising prospects have failed in advanced testing and the first to reach regulators — a medicine from Intercept Pharmaceuticals — was rejected last year.

A newer crop of medicines has followed. A MASH drug from Madrigal Pharmaceuticals won regulatory approval in March, for example. Other medicines from Akero Therapeutics and 89bio have shown some promise, too, though study results haven’t been as clear.

Yet they could be undercut by incretins. In February, Eli Lilly said tirzepatide, the drug it sells as Zepbound for weight loss, met its goal in a Phase 2 MASH study. At the time, Raymond James analyst Steven Seedhouse described the findings as the “best any [MASH] drug has ever shown in Phase 2 or Phase 3.”

Boehringer and Zealand’s drug, survodutide, may be another competitor. The drug, which the two companies are also developing for obesity, works somewhat differently than tirzepatide or Novo Nordisk’s Wegovy. Like those drugs, survodutide activates an insulin-regulating hormone called GLP-1. But the drug also targets a receptor controlling the hormone glucagon, which could be useful for treating MASH because it increases the liver’s metabolic rate.

The summary results disclosed so far are “roughly in line” with what Lilly reported, which may “lead to some pressure on [MASH]-focused companies,” Leerink Partners analyst Thomas Smith wrote in a client note.

But he and Jefferies analyst Michael Yee highlighted several caveats that make the findings harder to interpret. While comparing drugs across trials is difficult, Boehringer’s study had “less stringent” goals than the endpoints used by Lilly and others, Yee wrote. The company also enrolled a healthier study population, while its bar for declaring a liver scarring improvement is lower than in other trials, he added.

Fuller safety data are also needed to properly assess the results, Smith wrote.

Three Phase 3 studies of survodutide are underway in obesity. Results could come in 2025 and 2026, according to a federal database.

An experimental, triple-acting obesity drug from Eli Lilly helped some patients in a Phase 2 trial lose nearly a quarter of their body after 48 weeks, according to study results presented at a medical meeting in late June and published in the New England Journal of Medicine.

Patients treated with the highest dose of the drug, an injectable medicine called retatrutide, lost an average of 17.5% of their weight after 24 weeks, versus a 1.6% loss for placebo recipients. The effect size grew as time went on, with Lilly reporting a mean of 24.2% for those patients after 48 weeks.

As with other drugs like it, retatrutide was associated with gastrointestinal side effects such as nausea and vomiting. Wall Street analysts also flagged the potential for cardiovascular risk, as well as a type of skin sensitivity that occurred in 7% of treated patients compared to 1% of those who got a placebo.

Obesity drug development has quickly become one of the most competitive areas of biopharmaceutical research, with Lilly, Novo Nordisk and a group of would-be rivals racing for dominance of a market some analysts estimate to be worth more than $100 billion globally.

The annual meeting of the American Diabetes Association is the latest forum for the fast-moving competition, and one in which Lilly showcased its investments.

Already, Lilly has brought to market Mounjaro, an injectable medicine that’s approved for diabetes and could be cleared for use as an obesity treatment by the end of the year. Behind Mounjaro is an oral drug, orforglipron, that’s shown weight-loss effects in mid-stage testing that are comparable to injectable treatments.

Retatrutide is next in line and, unlike many obesity drugs in development, targets three hormones. Novo’s Wegovy acts on one, for instance, while Mounjaro homes in on two.

In the study presented at ADA, 338 patients received one of four different doses of retatrutide, or a placebo. At the start of the study, patients had a body-mass index of 30 or higher, or a BMI of 27 to less than 30 as well as a weight-related condition. The trial’s main goal was a change in body weight after 24 weeks. Secondary endpoints included a measure of weight after 48 weeks, as well as weight reductions of 5%, 10%, and 15% or more.

The drug’s effects on weight loss “triggered rare applause” from the crowd at the meeting and “may set a high bar for the next treatment wave” in obesity, wrote Jefferies analyst Peter Welford.

Welford also noted that all patients who received one of the top two doses lost at least 5% of their weight and nearly half of those on the highest dose lost more than 25%. “Remarkably the weight loss slopes continue to decline, suggesting greater effect in Phase 3 is possible,” he wrote.

The findings compare favorably to Mounjaro, which, in one of its Phase 3 trials, led to about a 20% weight loss after 48 weeks, wrote SVB Securities analyst David Risinger. But safety will be closely watched going forward. The study discontinuation rate was 16% for those on the highest dose. The appearance of a skin sensitivity side effect, cutaneous hyperesthesia, “drew attention,” Risinger noted. And “cardiovascular risk could be something to watch for,” he wrote, noting the instance in a single patient of a type of heart rhythm disruption called QT syndrome.

Lilly is investigating retatrutide in a large late-stage program involving at least four trials, among them studies in obesity and chronic weight management. Novo, meanwhile, has a newer medicine known as CariSegma that’s also in Phase 3 testing, and a pill that could be submitted to regulators this year.

An experimental pill developed by Novo Nordisk helped people with obesity lose 13% of their body weight after three months of treatment in a small clinical trial, the company said March 7, in a result one analyst described as among the best of any weight loss drug tested so far. 

The drug, called amycretin, is one of a handful of medicines Novo hopes can build on the success of its fast-selling obesity drug Wegovy. Unlike Wegovy, amycretin stimulates two gut hormones, GLP-1 and amylin, that affect appetite and blood sugar levels. It’s also taken orally, not via injections. 

The announcement comes as Novo looks to stave off a laundry list of competitors in a market Wall Street analysts expect to skyrocket in the coming years. Eli Lilly has already won approval of one such medicine, Zepbound, and a number of other large and small companies are advancing other prospects. Leerink Partners forecasts $158 billion in total yearly obesity drug sales in 2032.

Novo’s data are from a Phase 1 trial testing multiple doses of its drug against a placebo in 144 people. The results, disclosed at a March 7 investor presentation, only involved a group of 16 people on an unspecified dose. 

According to Novo, those who received a placebo lost 1% of their body weight over 12 weeks, meaning its drug was associated with placebo-adjusted weight loss of about 12% during the evaluation period. 

That measurement was “exploratory,” and thus didn’t meet the criteria for statistical significance. Comparing drugs across trials is also fraught with potential caveats. Nonetheless, the findings reverberated through the sector, as each development in the obesity drug chase is being closely watched by investors and analysts looking to see how each new medicine might measure up. 

Neither Wegovy nor Zepbound, for instance, were associated with more than 10% weight loss after 12 weeks in the studies underlying their approvals. A newer drug Novo’s working on, CagriSema, helped obese people lose 17% of their body weight at 20 weeks, while an injectable from Viking Therapeutics was associated with 15% weight loss in 13 weeks. 

A pill Lilly has in Phase 3 testing, meanwhile, hit 13% weight loss at 26 weeks. Structure Therapeutics’ experimental pill produced 5% weight loss in an early trial. 

Novo’s new results, then, are “at the highest end of weight loss seen” in testing of obesity drugs, wrote ISI Evercore analyst Umer Raffat. They also caused Novo’s Denmark-traded stock to surge, while shares of Viking, which is also developing an oral weight-loss medicine, fell.

However, Raffat cautioned that, if amycretin were to get to market, Novo could be limited by its manufacturing capacity. High doses of amycretin would require as much as 1 billion milligrams a week — far more than Novo currently produces — to meet the current demands of the U.S. market alone.

Pfizer will not advance a twice-daily dose of an experimental obesity drug into further testing after results from a mid-stage study showed high rates of gastrointestinal side effects and participant dropout. 

Treatment did lead to significant weight loss compared to placebo over the course of the Phase 2b study. Placebo-adjusted reductions in body weight ranged from 8% to 13% at 32 weeks, Pfizer said in a Dec. 1 statement. Discontinuation rates were more than 50% on some drug doses, however.

Moving forward, Pfizer will turn its focus to a once-daily version that’s currently being tested in a study meant to determine how the drug’s processed by the body. Data are expected in the first half of 2024.

Pfizer’s drug, known as danuglipron, is a GLP-1 agonist like in-demand obesity treatments from Novo Nordisk and Eli Lilly. But unlike those drugs, which are injections, danuglipron is taken orally, an advantage in convenience that Pfizer hopes will help it break into the fast-growing market.

The data released in December are a significant blow to those hopes, particularly after Pfizer stopped testing of another experimental obesity pill in June.

Louise Chen, an analyst at Cantor Fitzgerald, described the data as “disappointing” in a note to clients. According to Chen, investors were hoping to see a placebo-adjusted weight reduction of around 14% to 15%, which physicians Cantor has polled said would be enough to merit switching from injectable drugs like Novo’s Wegovy. 

Pfizer didn’t break out adverse event rates by danuglipron dose tested, but said up to 73% of participants experienced nausea, up to 47% vomiting and up to 25% diarrhea. The side effects were generally mild, the company said.

Notably, danuglipron wasn’t associated with signs of liver toxicity, which was the reason Pfizer had scrapped its other experimental pill, called lotiglipron. 

“We believe an improved once-daily formulation of danuglipron could play an important role in the obesity treatment paradigm, and we will focus our efforts on gathering the data to understand its potential profile,” said Mikael Dolsten, Pfizer’s top scientist and head of R&D, in the company’s statement.

Results from the ongoing pharmacokinetic trial of the once-daily version will “inform a potential path forward,” Dolsten added. 

Another setback could put Pfizer in the uncomfortable position of falling further behind in a fiercely competitive development race. Lilly, which recently won U.S. approval of its GLP-1 weight loss drug Zepbound, is also developing an oral obesity medicine called oforglipron that showed promise in a mid-stage trial last year. 

Pfizer’s CEO Albert Bourla has said he expects the market for GLP-1 drugs, which are also used to treat Type 2 diabetes, to eventually reach $90 billion in sales. He estimated oral versions could claim about one-third of that figure. 

Roche in December agreed to acquire biotechnology company Carmot Therapeutics in a deal that bulks up the Swiss pharmaceutical giant’s pipeline with a group of weight loss drugs in early clinical testing.

Roche will pay $2.7 billion upfront for the Berkeley, California-based Carmot. Roche could owe as much as $400 million more in future payments to Carmot shareholders, among them The Column Group and RA Capital, if certain milestones are met. The companies expect the acquisition to close in 2024.

The deal hands Roche a trio of drugs in human testing for obesity, an area of pharmaceutical research that has been catalyzed by the success of weight loss medicines like Wegovy and Zepbound. Their progress has fueled a gold rush among large drugmakers, a number of which are either advancing in-house medicines or inking deals to acquire new prospects.

Best known for its cancer drugs and diagnostics, Roche is now solidly among them. The Swiss company hasn’t had the type of medicines, called incretins, that have been most sought after in this current obesity drug boom. The acquisition of Carmot will fill that gap, adding a trio of drugs in early testing, including two that are either in Phase 2 testing or ready for a mid-stage trial.

The two Carmot drugs in Phase 2 trials act on two insulin-boosting hormones called GLP-1 and GIP, similar to Zepbound. One is administered once weekly through a subcutaneous injection and in development for people with or without Type 2 diabetes. Data from a small trial, presented at a medical meeting last year, were “competitive, albeit early,” wrote Jefferies analyst Peter Welford, in a December note to investors.

Carmot also has a daily treatment for Type 1 diabetics in mid-stage testing and an oral treatment in Phase 1.

Roche claims all three could be “best in class.” The Swiss company also noted their potential for use in tandem with muscle-preserving drugs in its pipeline, as well as possible other uses treating eye or brain diseases.

Still, Carmot’s drugs are behind next-generation treatments from Eli Lilly and Novo Nordisk, as well as rivals from other biotech companies. Both Lilly and Novo have acquired obesity drug startups to stay ahead in the field, too.

Roche management “foresees a fragmented obesity market, with muscle strength, not just lean mass preservation, as a key opportunity,” Jefferies analyst Welford wrote.

“The broad Carmot portfolio offers different routes of administration and opportunities to develop combination therapies that treat obesity and potentially other indications,” said Roche Chief Medical Officer Levi Garraway, in a statement.

Carmot raised about $371 million from private investors, according to regulatory filings. The Column Group is by far its largest investor, holding a roughly 40% stake in the company.

AstraZeneca is recommitting to the GLP-1 drug development race, announcing Nov. 9 a bet on an experimental therapy from China-based biotech Eccogene that’s in early clinical testing.

AstraZeneca will pay $185 million upfront for rights to the drug, dubbed ECC5004, and promised up to $1.8 billion more if certain clinical, regulatory and commercial milestones are met. AstraZeneca will have global development and commercial rights outside of China, while the two companies will share rights in China.

AstraZeneca gained rights to the first once-weekly GLP-1 drug, Bydureon, in 2013 through a transaction with Bristol Myers Squibb. Eli Lilly’s Trulicity and Novo Nordisk’s Ozempic have dominated in recent years, however, while AstraZeneca’s focus in diabetes shifted to Farxiga, its second best-selling product in 2023.

Wall Street analysts and even big pharmaceutical company CEOs like Pfizer’s Albert Bourla are making ambitious sales forecasts for GLP-1 drugs, predicting annual global sales could reach as high $90 billion by the end of the decade. The rosy predictions have spurred a rush of investment by companies not already in the field.

While GLP-1 drugs’ ability to lower blood sugar in people with diabetes is well-established, they’re now in the spotlight due to the powerful weight loss benefits of newer versions like Novo Nordisk’s Wegovy.

A new entrant, Lilly’s diabetes treatment Mounjaro, is catching up quickly. In November that drug gained U.S. approval as a weight loss treatment and is now sold by Lilly under the name Zepbound.

AstraZeneca’s cardiometabolic business is its second-biggest after oncology, pulling in nearly $8 billion in sales so far in 2023. It’s led by Farxiga and blood thinner Brilinta, with sales of $4.4 billion and $996 million respectively through the first nine months of 2023. (Both could lose market exclusivity soon as their main U.S. patents are set to expire in the next few years.)

Farxiga, a pill that lowers blood sugar through a different mechanism than the GLP-1s, has been a big seller in part by showing it protects heart and kidney health.

If successful, ECC5004, an oral agent, could help AstraZeneca compete in the GLP-1 market. Today, the only oral GLP-1 drug is Novo’s Rybelsus. Pfizer discontinued one of its oral GLP-1 candidates in June because of liver safety concerns.

“We believe [ECC5004] could offer alternatives to current injectable therapies both as a potential monotherapy as well as in combination for cardiometabolic diseases such as Type 2 diabetes, as well as for obesity,” said Sharon Barr, AstraZeneca’s head of biopharmaceuticals R&D, in a statement.

AstraZeneca said the Phase 1 data so far show a “differentiating clinical profile” with “good tolerability and encouraging glucose and body weight reduction across the dose levels tested compared to placebo.”

The company had its own GLP-1 agonist in Phase 1 testing for diabetes, but discontinued it last year as part of a “strategic portfolio prioritization.” It has another in testing for non-alcoholic steatohepatitis.