As high prices and supply issues drive consumers to alternative markets for GLP-1s, physicians aren’t too interested in using these therapies to treat conditions like heart disease risk that have existing cheap standards of care.
With biopharma pouring more money than ever into weight loss medicines, physicians would like to see improved GLP-1 drugs. But the goals of the two parties are not in full alignment, according to a new study from strategic advisory firm DNB Markets and Back Bay Life Science Advisors.
In a survey of 50 physicians, doctors overwhelmingly cited efficacy and safety, plus access as the most important factors in prescribing decisions.
The survey found that 94% of the doctors ranked the benefit-safety profile as one of the most important factors in prescribing a weight loss medication, followed by 92% who also flagged insurance coverage and out of pocket expenses. Less important considerations to doctors as they write a script include the availability of patient support programs, injection frequency and risk of thyroid cancer.
“Cost and insurance coverage play an outsized role in guiding the choice of physicians and patients between GLP-1 options. For some, this is an even more important consideration than clinical efficacy,” according to the report.
Physicians also seem to be clamoring for drugs with fewer side effects, Peter Bak, partner and managing director of Back Bay Life Science Advisors, told BioSpace. The two currently approved medications, Novo Nordisk’s Wegovy and Eli Lilly’s Zepbound, commonly cause gastrointestinal side effects such as nausea and vomiting.
“What came through loud and clear, at least from the data, is they still see some room for improvement on the GLP-1 class,” Bak said.
The industry is working to do just that, to be sure, with investment flooding in to develop drugs that lead to greater and better-quality weight loss. And in some ways, these efforts could deliver what the surveyed physicians are after. In other ways, biopharma seems to be channeling resources toward programs that doctors say they don’t have much use for, such as applying GLP-1s outside of metabolic disease.
Why So Many Patients Quit GLP-1s
The surveyed physicians reported that about one-thirdof their patients discontinued GLP-1 treatment by six months, mainly due to side effects and the cost. A previous report published in JAMA Open Network put the discontinuation rate at more than half of patients at one year and 72% at the two-year mark.
The Back Bay survey pinpointed lack of insurance coverage as the top reason that patients stop taking GLP-1s, with 54% of physicians ranking this as reason number one. This was followed by drug availability, with 40% ranking it among the top three considerations, according to the report.
The reasons differed when it came to switching from one GLP to another. The top reason for switching medications was improved weight loss benefit and overall efficacy, followed by a less expensive option.
Perhaps surprisingly, ease of administration was not a high concern for the physicians and was not cited among the reasons for discontinuations. “It didn’t interestingly pop up as a huge reason for people discontinuing relative to lack of response, tolerability [and] access,” Bak said of injectable medications.
On the surface this may seem incongruent with pharma’s recent push to develop oral weight loss medications. More than 55% of deals examined by the firm in the survey named oral delivery as a factor. But Bak says it actually makes sense, because although delivery method was not cited as a top reason for patient discontinuations, convenience can improve compliance. Oral medications can also be manufactured at scale and potentially lower costs, which hits on another major item on physicians’ wish lists.
Few of the deals examined in the report actually included additional manufacturing capabilities. But market leaders Eli Lilly and Novo Nordisk have been boosting their manufacturing capacity to keep up with demand. In addition, Lilly recently announced that it has stockpiled $550 million worth of its up-and-coming oral weight loss drug orforglipron, even though the product is at least a year or more from launch.
Orals could also provide a “franchise strategy,” Bak suggested,meaning a patient could start on an injectible and then move on to an oral for long-term maintenance after initial weight loss.
Meanwhile, debate continues to swirl about how GLP-1s affect muscle mass and what is safe for patients as they lose weight. Many companies are already looking at new mechanisms that can stimulate muscle. The Back Bay report cited Lilly and Versanis’ bimagrumab and Regeneron’s trevogrumab in combination with garetosmab as options that could help preserve muscle mass.
Little Enthusiasm for GLP-1s Beyond Weight Loss
One area where physicians did seem to diverge from industry was the idea of using GLP-1s for indications beyond weight loss or diabetes. Novo Nordisk’s Wegovy has been approved for reducing cardiovascular risk, while Eli Lilly’s Zepbound can now be used for sleep apnea. Both companies are working fast to run clinical trials for other diseases, from metabolic dysfunction-associated steatohepatitis (MASH) to Alzheimer’s and kidney disease.
But using these drugs for other conditions—which may already be well served by cheaper alternatives—is not top of mind for doctors on the front lines. Companies may also see resistance from payers on this front, too.
The study also showed continued heavy investment into the GLP-1 mechanism. In an examination of deals between January 2019 and December 2024, 12 revolved around the this strategy. The remaining deals split across other possible mechanisms such as activin and myostatin, GIP, dual GIP/GLP-1 and amylin.
“Despite Novo Nordisk and Eli Lilly’s intense four-year rivalry in the GLP-1 market since Wegovy’s launch in 2021, the industry’s narrow focus on GLP-1 and GLP-1 combination therapies appears inconsistent with the potential for diverse approaches to obesity treatment,” the report explains. “Nevertheless, feedback from our physician survey underscores a clear demand for improved GLP-1 safety and tolerability, signaling that investment capital is strategically aligning with critical market needs.”
Bak likened the frenzied investment to the wave of deals that followed the PD-1 immunotherapy boom many years ago. Companies piled on to try to match Merck’s success with Keytruda, but ultimately just a handful of assets with this mechanism were approved. Companies then moved to pairing and developing combo approaches.
Bak wonders if the deal flow in obesity will now move towards a “landgrab for secondary mechanisms.”
