It is well known that obesity increases the risk of developing a wide range of health problems, but data suggests that it may not just be excess weight that increases risk.
The drugs may not be as effective in obese people, studies suggest, because even though people with a lot of body fat metabolize drugs differently, there is no need to include them in research trials. The prescribed doses may therefore be too high in some cases and persist too long in others.
And with more than 40% of Americans now living with obesity and a wide range of popular medications potentially affected, this dosage gap is likely to have a major impact on the lives and health of many people, several experts said .
Studies have shown that people who regularly take medications for birth control or to combat high cholesterol, depression, or panic disorders may receive the wrong amount of 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-authored a recent paper on the subject.
Dietz attributes weight bias to a lack of attention to a large 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 hit her in 2019 was deep and persistent and medication just wasn’t helping.
“I tried drug after drug after drug,” said Gilbert, who works for the local public library system. “It makes me wonder if my weight has anything to do with it.”
She ultimately overcame her depression through therapy, a strong support system, more stability, and the passage of time after a significant loss.
The dosage of antipsychotic medications, like the one Gilbert took for months without effect, is not changed by prescribing doctors based on the patient’s weight. But body fat affects how quickly the body processes brexpiprazole, an antipsychotic sold under the brand name Rexulti.
A person with a lot of body fat will process drugs like brexpiprazole more slowly than a person who has less and will therefore need a higher dose to get the same benefit, said Dr. Caroline Apovian, author of a poster on drug trials and obesity presented. this month at ObesityWeek 2023 in Dallas.
“Dosing and pharmacokinetics depend on when and how much enters the bloodstream and it is in the bloodstream that medications have their effects,” said Apovian, who also co-directs the Center for Weight and Health Management. wellness at Brigham and Women’s. Boston Hospital.
“If you are not testing large patients and administering a drug based on blood entry to patients with ‘normal’ body fat, doses tailored to normal body weight may not be effective for obese people.”
Medications also hang around longer in a bulky body, potentially causing side effects or interacting with other medications.
But Apovian and his co-authors showed that more than half of current drug trials do not mention body mass index in their official descriptions on clinical trials.gov.
When body mass, a typical measure of obesity, is mentioned, it is usually used to completely exclude obese people from participating in a trial, they found.
“It’s crazy,” said Ted Kyle, another poster author, who writes the blog ConscienHealth. “It’s not like you have to do extensive studies with every drug, but at a minimum we should say, ‘Oh, would this be a problem?'”
Lack of regulation
Regulators do not require drugs to be specifically tested in people with a large amount of body fat, so even if doctors wanted to prescribe a higher dose, they would not know how much to administer or which drugs are most likely to cause harm. ‘be affected, Apovian and others. say the experts.
The Food and Drug Administration, which regulates drug approval and sets requirements for drug trials, recognizes the problem.
FDA Commissioner Dr. Robert Califf speaking at a workshop a year agosaid there is an “information gap” about how medications affect obese people and they are often underrepresented in research trials.
He said he hoped workshop participants from the FDA, the University of Maryland and elsewhere would help fill this information gap “to ensure that we move toward appropriate drug dosing in the obese patient.
Obese people are not necessarily excluded from clinical trials, but they may be reluctant to participate because of their poor experience with the medical system. They may also be excluded because of other health issues they face, such as high blood pressure or diabetes. It’s also possible that the companies conducting these trials simply aren’t analyzing obesity, even though they consider important factors related to gender, age, and race.
Regulators have said obesity adds to trial variability, which is why companies are not required to include obese people at the start. But Dietz, of the STOP Obesity Alliance, said that’s precisely why they should be included.
Besides, he added, half-jokingly, he would expect drug companies to want to identify patients who would benefit from a higher dose of medication, because they might be charged more.
Dr. Fatima Cody Stanford, an obesity medicine specialist at Massachusetts General Hospital in Boston, praised companies involved in COVID-19 vaccine trials for including a high percentage of obese people. If they could do it, given the time constraints they were under, then other companies could do it too, she said.
“I’m not going to let them pass on this,” she said of other pharmaceutical companies and other trials. At least 40% of adults and 20% of children participating in clinical trials of all kinds of drugs, not just those aimed at obesity, must have a higher body mass index, she said.
Cody Stanford said she was particularly troubled by the lack of data on drugs like brexpiprazole, intended for a population already facing a stigmatizing mental health problem.
People with schizophrenia or depression are more likely to have obesity than the general population. A 2017 study found that 59% of people with schizophrenia had obesity. Medications used to treat schizophrenia are known to increase body weight.
“There are so many levels of nastiness that can happen here if the tests aren’t tested well and don’t reach effective levels in obese people,” she said. “It’s a recipe for disaster in a situation that is not well understood, even if it is well handled.”
Potential consequences
Dietz and several colleagues published an article in August showing that a number of commonly used drugs are fat-soluble, meaning it would take longer for them to reach an effective dose in the blood of someone with a lot of body fat.
The article lists a number of common medications its authors believe could be affected by a person’s body size:
- atorvastatin, a cholesterol-lowering drug;
- the beta blocker metoprolol, used to treat high blood pressure;
- omeprizole, a heartburn medication;
- the antidepressant sertraline;
- alprazolam for anxiety and panic disorder;
- ibuprofen, used to treat pain, fever and inflammation;
- ergocalciferol, a vitamin D analogue;
- ethinyl estradiol and norethindrone, used in birth control pills;
- and levonorgestrel, used to prevent pregnancy after contraceptive failure.
In another example provided in this study, which appeared in the journal “Health Affairs,” the antifungal drug posaconazole has a warning in its packaging indicating that it may be ineffective in obese patients at the usual dose. But there are no instructions on the appropriate dose. And because it lasts longer in a larger person’s body than in a non-obese person, it can interact with other medications given at the same time.
If these medications are not tailored to the person’s body fat, they may be less effective, if at all, said Dietz, who also directs the Sumner M. Redstone Global Center for Health Prevention and Wellness. George Washington University Milken Institute School of Public Health.
“The provider’s response might be, ‘Why aren’t you taking the medicine?’ (They) blame the patient when in fact it’s the pharmacodynamics that should be blamed.”
What Dietz wants is for every doctor who treats an obese patient to know whether the medication they prescribe is potentially affected by that patient’s body weight. “This should be a priority when writing a prescription,” he said, although he admits it’s unclear how to adjust the drug’s dosage.
For her part, Gilbert said she naturally assumed that because her medications had been prescribed by a doctor, they had been researched and dosed correctly. Fortunately, she overcame her period of suicidal thoughts without taking action, but others, given an ineffective dose, may not be able to do so.
“It’s definitely something (people need) to be aware of so it doesn’t continue to happen,” she said. “Starting with judgments or assumptions that we don’t care about being overweight or that it’s just a choice – and that because we are overweight, we don’t deserve adequate medical care.”
If that’s an assumption that anyone has,” Gilbert said. “It’s not good.”
VSContact Karen Weintraub at kweintraub@usatoday.com.
USA TODAY’s coverage of patient health and safety is made possible in part by a grant from the Masimo Foundation for Ethics, Innovation and Competition in Health Care. The Masimo Foundation does not provide editorial contributions.
