More than 40 percent of American adults are considered obese, but the drugs many take are rarely tested on larger bodies.
This is because they are not required to be included in drug studies. And often, they are explicitly excluded.
“Clinical trials and dosing instructions do not always guarantee that medications will be safe and effective for obese people,” said Christina Chow, a drug researcher who has reported on the challenges of addressing obesity. in drug development. “There’s no real point in studying them.”
Many widely prescribed medications and over-the-counter medications work differently in obese people, but it is often unclear exactly how and in what dose. Research suggests this could include antibiotics and antifungal medications used to treat serious infections, synthetic hormones used in Plan B emergency contraception and even ibuprofen, the common painkiller sold as Advil .
The U.S. Food and Drug Administration and the National Institutes of Health – agencies that regulate and fund drug testing – are now emphasizing research gaps. At a workshop last year, FDA Commissioner Dr. Robert Califf acknowledged an “evidence gap” on how drugs work in obese patients. The NIH is now encouraging researchers to consider the impact of excluding obese people in their studies, a spokesperson said.
At a recent medical conference, Chow presented a review of more than 200 studies of new drugs conducted in the United States last year. Of these, almost two-thirds did not mention weight or body mass index – a common assessment of obesity – meaning they would not ensure inclusion of obese people, a- she declared.
Studies that cite weight have most often been used to exclude obese people from participation, said Chow, who works for Emerald Lake Safety, a California company that investigates serious drug reactions. People with a body mass index or BMI of 30 or more are considered obese.
Historically, certain populations have been excluded from testing due to fear of harm, including pregnant people and children. Women, racial and ethnic minorities, and older adults have also been underrepresented before recent efforts to boost diversity.
The reasons for excluding obese people are old and varied, said Dr. Caroline Apovian, a researcher at Brigham and Women’s Hospital in Boston and co-author of Chow’s study.
Participants willing to enroll in studies are often smaller and not reflective of the general population, she noted. And researchers often fear that the health complications that can accompany obesity will alter the results of their work.
“Sometimes obese patients have many more comorbidities than others. They will have more diabetes, more heart disease, more strokes,” she said.
But if drugs are not studied in a pathology that affects 42% of the American population, the real consequences can be disastrous, experts believe.
Some medications may concentrate in fatty tissues and not in the bloodstream. That means there will be less medication in the bloodstream, leading to undertreatment, Apovian said.
Other medications stay longer in the bodies of obese people. This could lead to harmful drug interactions if another medication is added too soon.
An antipsychotic called Rexulti is often prescribed to people with schizophrenia or major depressive disorder, Chow noted. Research has shown that in obese patients, it may take much longer to reach the concentration of Rexulti needed to be effective. As a result, many patients — and their doctors — may stop treatment too soon or conclude that the medication is not working.
“Failing to treat or undertreat schizophrenia can be dangerous to themselves and those around them,” Chow said.
The emergency contraceptive medication Plan B One-Step is another example. Studies suggest that levonorgestrel, the active drug, may not work as well in people with obesity, which could lead to treatment failure and pregnancy, said Dr. Alison Edelman, an obstetrician-gynecologist and researcher at Oregon Health & Science University, who studies contraception and obesity. But the FDA says the data is limited and conflicting, and so there isn’t enough evidence to require a label warning.
Even a drug as common as ibuprofen, sold under the name Advil, may not relieve pain in people of higher weight when taken as directed, research shows.
But without adequate testing and clear instructions, doctors won’t know how to adjust dosing in cases of obesity, said Dr. Colleen Tenan, a board member of the Association of Clinical Research Professionals.
“It’s very difficult to be a doctor and say I’m going to prescribe medications outside of normal limits,” she said.
Change is coming, but progress is slow, Edelman said. In 2019, the FDA released draft guidance on hormonal contraception that requires study sponsors to lift restrictions on body mass index and include obese women. Although the guidance is not final, it has already changed the way she and other researchers structure their studies, she said.
“It’s just something we need to reduce because it’s very important,” she said. “Because unless we see representation in our study population, we won’t get treatments that work well for individuals.”
In the meantime, Apovian said patients can ask their doctor whether the standard dose of a medication is appropriate for their weight. Doctors may not know it, but it could start an important conversation about effective treatment.
“It’s a big deal,” she said. “It can be important for patients to speak out. »
The Associated Press Health and Science Department receives support from the Howard Hughes Medical Institute’s Science and Education Media Group. The AP is solely responsible for all content.