Here’s the skinny on obesity drugs
Several critical advances this month will go a long way toward making obesity drugs more widely available to patients: more consistent access, improved affordability and global conviction that these potentially lifelong treatments are worth the cost to the health care system.
Resolving those issues matter at both the individual level — enabling people to take drugs that could ultimately save their lives — and the societal one, delivering those treatments without bankrupting the health care system.
Progress began with the Food and Drug Administration’s approval for Eli Lilly & Co.’s tirzepatide, now known as Zepbound. European regulators took a step closer to their own formal approval to use the drug to treat obesity.
Then, in a shot across the bow to Novo Nordisk, Lilly set Zepbound’s list price at a roughly 20% discount to Wegovy. While the list price rarely reflects what patients or their insurers pay for the drug, it’s a signal that companies are prepared to compete a little on cost as they battle for dominance in a market expected to reach $100 billion.
Both companies, meanwhile, outlined plans to better meet surging demand, which has led to chronic shortages of their drugs. Novo is spending $6 billion to expand manufacturing capacity, including for its obesity portfolio. And on a call with reporters after the Zepbound approval, Lilly CEO David Ricks said the company was still on track to double its 2022 capacity by the end of this year, and it’s “not stopping there.”
But the most important advance came earlier this month, when clinicians at the American Heart Association’s annual meeting presented data from a four-year trial dubbed SELECT (Semaglutide Effects on Heart Disease and Stroke in Patients With Overweight or Obesity). The goal of the study, which was simultaneously published in the New England Journal of Medicine, was to prove that Wegovy, which unquestionably helps users lose substantial weight, can also improve their health in other ways.
The answer is yes.
Taking Wegovy lowered the risk of heart attacks and strokes by 20%, a result Novo Nordisk had reported in a news release in August. But cardiologists wanted to see the more granular data — details like the type of patient in the trial, whether people stopped taking the drug, the types of cardiovascular events that were avoided, and whether the drug improved ancillary health measures like triglycerides, blood pressure and inflammatory markers.
What they saw impressed them. In addition to lowering the risk of heart attacks and strokes, the drug seemed to lower the risk of all causes of death. Notably, those benefits began to emerge within the first months of taking Wegovy, even before people had started to lose substantial weight.
“This is a game changer of a study,” said Amit Khera, director of UT Southwestern Medical Center’s preventive cardiology program.
It should also persuade at least some insurers that have resisted covering these expensive drugs that they have real value.
“These are exactly the data we need to create some pressure to say, ‘This is not just an obesity drug,’ ” Khera said. “All cause mortality being lowered? It’s pretty hard to ignore that.”
Still, a few lingering questions can’t be ignored. For one, a sizable portion of volunteers in the trial stopped taking the drug (some 16.6% of people in the semaglutide arm compared with 8.2% in the placebo arm). The study can’t confirm whether any heart protective benefits persisted, especially if subjects went on to regain the weight they had lost.
And the study can only prove the drug lowers risks in people with a history of cardiovascular disease. While that covers a lot of people, more work needs to be done to understand whether that benefit could extend to people with obesity who have yet to display heart ailments.
And it’s also important to note that these results might not be broadly applicable to the entire class of drugs, called GLP-1 agonists. The field is still trying to understand the underlying mechanism that connects weight loss and lowered cardiovascular risk to treatment with GLP-1.
For example, given the benefits that emerged early on in the trial, does the degree of weight loss matter? And how much is GLP-1 itself responsible for the benefits? Wegovy only mimics the action of the GLP-1 hormone, but Zepbound mimics both GLP-1 and another hormone called GIP, and still other combinations are in the works.
“This is a much-needed tool in our toolbox to help attenuate this rising tide of diabetes and obesity,” Harvard Medical School cardiologist James Januzzi said. He pointed out that many of the gains made over the last few decades in reducing heart disease had been lost because of the rise in obesity and diabetes.
Even with lingering unknowns, it’s fair to say that the GLP-1 therapies will transform the way medicine is practiced across myriad disciplines, not just obesity. The cardiovascular study, along with companies’ clear intention to keep rolling out more drugs and more data, accelerates the momentum for these important treatments.