For the 40% of Americans with obesity, medications may be given at wrong dose

It's well known that having obesity increases the risk of a wide range of health conditions, but data suggests it may not be just the extra weight that adds risk.

Medications may not work as well on people with obesity, studies suggest, because, although people with a lot of body fat metabolize drugs differently, they aren't required to be included in research trials. So prescribed doses may be too high in some cases and linger too long in others.

And with more than 40% of Americans now living with obesity, and a wide range of popular drugs potentially affected, this dosing deficit is likely having a major impact on many people's lives and health, several experts said.

Studies have found people taking regular medication for birth control, or to combat high cholesterol, depression or panic disorders might be getting the wrong amount of needed medication.

It's "a huge problem for the population," said Dr. William Dietz, who directs the STOP Obesity Alliance at George Washington University in Washington, D.C., and co-wrote a recent paper on the topic.

Dietz blames weight bias for the lack of attention to a major portion of the population. "I think it's because people don't care about obesity."

Lived experience

For Courtney Gilbert, of Big Rapids, Michigan, the depression that overtook her in 2019 was deep and lingering and drugs simply weren't helping.

"I tried medication after medication after medication," said Gilbert, who works for the local public library system. "This coming up does make me wonder if my weight had something to do with it."

She eventually overcame her depression with therapy, a strong support system, more stability and the passage of time after a major loss.

Courtney Gilbert got no help from a drug she was taking for her depression. Now she wonders if she was under-dosed for her body weight and that's why the drug didn't work.
Courtney Gilbert got no help from a drug she was taking for her depression. Now she wonders if she was under-dosed for her body weight and that's why the drug didn't work.

The dosage of antipsychotic medications, like the one Gilbert took for months to no effect, does not get altered by prescribing doctors based on a patient's weight. But body fat affects how quickly the body processes the antipsychotic brexpiprazole, sold under the brand name Rexulti.

Someone with a lot of body fat will process drugs like brexpiprazole more slowly than a person with less and will therefore need a higher dose to get the same benefit, said Dr. Caroline Apovian, an author of a poster on the drug trials and obesity presented this month at ObesityWeek 2023 in Dallas.

"The dosing and the pharmacokinetics all have to do with when and how much enters the bloodstream and it's in the bloodstream that the drugs have their effects," said Apovian, who also co-directs the Center for Weight Management and Wellness at Brigham and Women's Hospital in Boston.

"If you don't test patients of size and you're dosing a drug based on the bloodstream entrance of patients with 'normal' body fat ‒ the doses for normal body weight might not be effective for those with obesity."

Medications also hang around a large body longer, potentially causing side effects or interacting with other medications.

But Apovian and her co-authors showed that more than half the drug trials underway do not mention body mass index in their official descriptions on

When body mass, a typical measure of obesity, is mentioned, it is generally used to exclude people with obesity from being in a trial altogether, they found.

"It's nuts," said Ted Kyle, another of the poster's authors, who writes the blog ConscienHealth. "It's not like you have to do deep studies with every drug, but at minimum, we ought to be saying, 'Oh, would this be a problem?'"

Lack of regulation

Regulators don't require that drugs be specifically tested in people with large amounts of body fat, so even if doctors wanted to prescribe a higher dose, they wouldn't know how much to give or which drugs were most likely affected, Apovian and other experts said.

The Food and Drug Administration, which regulates drug approvals and sets requirements for drugs trials, acknowledges the problem.

FDA Commissioner Dr. Robert Califf, speaking at a workshop a year ago, said there's a "deficit of information" about how drugs affect people with obesity and that they're often underrepresented in research trials.

He said he hoped workshop participants from FDA, the University of Maryland and elsewhere would help close this information gap "to ensure that we're making progress toward appropriate drug dosing in the obese patient."

People with obesity aren't necessarily excluded from clinical trials, but they may be reluctant to participate because of poor experiences with the medical system. They may also be excluded because of other health issues they face, such as high blood pressure or diabetes. Or it's possible that companies running the trials simply do not analyze obesity even as they consider sex, age and race important factors.

Regulators have said obesity adds to variability in trials, which is why companies aren't required to include people with obesity at the outset. But Dietz, from the STOP Obesity Alliance, said that's precisely why they should be included.

Also, he said, only half-jokingly, he'd expect drug companies would want to identify patients who would benefit from a higher dose of medications because they could be charged more.

Dr. Fatima Cody Stanford, an obesity medicine specialist at Massachusetts General Hospital in Boston, praised the companies involved in COVID-19 vaccine trials for including a large percentage of people with obesity. If they could do it, with the time pressure they were under, then other companies can do it, too, she said.

Dr. Fatima Cody Stanford
Dr. Fatima Cody Stanford

"I'm not going to give them a pass on this," she said of other drug companies and trials. At least 40% of adults and 20% of children in clinical trials for all sorts of drugs, not just those addressing obesity, need to be of a higher body mass index, she said.

Cody Stanford said she's particularly disturbed by the lack of data for drugs like brexpiprazole, which are intended for a population already facing a stigmatizing mental health condition.

People with schizophrenia or depression are more likely to have obesity than the general population. One 2017 study found that 59% of people with schizophrenia had obesity. Drugs used to treat schizophrenia are known to increase body weight.

"There are so many layers of badness that can happen here if it's not tested well and doesn't reach effective levels in people with obesity," she said. "This is a recipe for disaster in a condition that's not well understood, even if it is well treated."

Potential consequences

Dietz and several colleagues published a paper in August showing that a number of commonly used drugs are fat soluble, meaning they would take longer to reach an effective dose in the bloodstream of someone with a lot of body fat.

The paper listed a number of common drugs its authors thought might be affected by a person's body size:

  • atorvastatin, a cholesterol-lowering medication;

  • the beta blocker metoprolol, used to treat high blood pressure;

  • the anti-heartburn medication omeprizole;

  • the antidepressant sertraline;

  • alprazolam for anxiety and panic disorder;

  • ibuprofen, used to treat pain, fever and inflammation;

  • the vitamin D analogue ergocalciferol;

  • ethinyl estradiol and norethindrone, used in birth control pills;

  • and levonorgestrel, used to prevent pregnancy after birth control failure.

In another example provided in that study, which appeared in the journal "Health Affairs," the anti-fungal drug posaconazole has a warning in its packaging that it might be ineffective in patients with obesity at the typical dosage. But there's no instruction about what the right dose might be. And because it lasts in the body of a larger person longer than in a person without obesity, it might interact with other drugs given at the same time.

If these drugs are not adjusted for the person's body fat they may be less effective or not effective at all, said Dietz, who also directs the Sumner M. Redstone Global Center for Prevention and Wellness at George Washington University's Milken Institute School of Public Health.

"The provider's response might be, 'Why aren't you taking the drug?' (They) blame the patient when in fact, it's the pharmacodynamics that should be blamed."

What Dietz wants is for every doctor who treats a patient with obesity to know if the drug they are prescribing is potentially affected by that patient's body weight. "It should be top-of-mind when writing a prescription," he said, though he admits it's unclear how to adjust drug dosage.

For her part, Gilbert said she naturally assumed because her medication had been prescribed by a doctor that it had been researched and dosed properly. Luckily, she got through her period of suicidal thinking without acting on it, but other people, given an ineffective dose, might not.

"It's definitely something that (people need) to be made aware of so it doesn't keep happening," she said. "Starting with judgments or assumptions that we don't care that we're overweight or this is just a choice ‒ and that because we're overweight we don't deserve adequate medical care."

If that is an assumption someone has," Gilbert said. "That's not okay."

Contact Karen Weintraub at

Health and patient safety coverage at USA TODAY is made possible in part by a grant from the Masimo Foundation for Ethics, Innovation and Competition in Healthcare. The Masimo Foundation does not provide editorial input.

This article originally appeared on USA TODAY: Drug trials don't require people with obesity, so dosing may be wrong