More than 40% of American adults are obese, but the medications many take are rarely tested on larger bodies.
This is because it is not necessary to include it in drug studies. Often, they are outright excluded.
“Clinical trials and dosing instructions do not always guarantee that drugs will be safe and effective for people with obesity,” said Christina Zhao, a pharmaceutical researcher who wrote a report on the challenges of taking obesity into account when developing drugs. “There is no real focus on their studies at all.”
Many widely prescribed and over-the-counter medications work differently in obese people, but it’s often not clear how and at what dose. Research suggests this may 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 US Food and Drug Administration and National Institutes of Health — the agencies that regulate and fund drug testing — are putting a new focus on gaps in research. At a workshop last year, FDA Commissioner Dr. Robert Califf acknowledged there was a “lack of evidence” about how the drugs work in obese patients. The National Institutes of Health is now encouraging researchers to consider the impact of excluding obese people in their studies, an NIH spokesperson said.
At a recent medical conference, Zhao presented a review of more than 200 studies of new drugs in the United States in the past year. She said nearly two-thirds of these failed to mention weight or body mass index – a common assessment of obesity – meaning they would not ensure obese people were included.
Studies that cited weight were often used to exclude obese people from participating, said Zhao, who works for Emerald Lake Safety, a California company that investigates severe drug interactions. People with a BMI or BMI of 30 or higher are considered obese.
Historically, certain populations have been excluded from testing for fear of harm, including pregnant women and children. Women, racial and ethnic minorities, and older adults have also been underrepresented in recent efforts to promote diversity.
The reasons for excluding people with obesity are long-standing and varied, said Dr. Carolyn Apovian, a researcher at Brigham and Women’s Hospital in Boston and co-author of Chow’s study.
She noted that participants willing to enroll in studies are often smaller in size and do not reflect the general population. Researchers often worry that health complications that may accompany obesity will affect the results of their research.
“Sometimes patients with obesity have more comorbidities than others. They will have more diabetes, more heart disease, more strokes,” she said.
But if the drugs haven’t been studied for a condition that affects 42% of the U.S. population, the real-world consequences could be dire, experts say.
Some medications can be concentrated in fatty tissue rather than in the bloodstream. This means there will be less drug in the blood, leading to undertreatment, Apovian said.
There are other medications that remain in the body for a longer period in people who suffer from obesity. This may result in harmful drug interactions if another medication is added too soon.
Zhao noted that an antipsychotic medication called Rexulti is often prescribed to people with schizophrenia or major depressive disorder. Research has shown that obese patients may take significantly longer to reach the concentration of Rexulti needed to be effective. As a result, many patients – and their doctors – may stop treatment too early or conclude that the medication is not working.
“Under-treating or under-treating schizophrenia may pose a risk to themselves and to the people around them,” Zhao said.
The emergency contraceptive drug 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 drug failure and pregnancy, says Dr. Allison Edelman, an obstetrician-gynecologist and researcher at Oregon Health & Science University, who studies methods. Contraception and pregnancy. obesity. But the FDA says the data is limited and conflicting, so there is not enough evidence to require a warning on the label.
Research has shown that even a common medication like ibuprofen, sold as Advil, may not relieve pain in heavier people when taken as directed.
But without adequate testing and clear instructions, doctors won’t know how to adjust obesity doses, says Dr. Colleen Tynan, 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 you prescriptions that are outside the normal range,'” she said.
Edelman said change is coming, but progress is slow. In 2019, the FDA issued draft guidance on hormonal contraception requiring study sponsors to lift restrictions on BMI and inclusion of obese women. She said that although the guidelines are not final, they have already changed the way she and some other researchers organize their studies.
“It’s just something we have to get rid of because it’s so important,” she said. “Because unless we see representation in our study population, we’re not going to end up with treatments that work well for individuals.”
In the meantime, Apovian said patients can ask their doctors whether the standard dose of the drug is appropriate for their weight. Doctors may not know it, but it can start an important conversation about effective treatment.
“This is a big issue,” she said. “It may be important for patients to talk.”
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