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Tag: older patients

  • Older Americans Are About to Lose a Lot of Weight

    Older Americans Are About to Lose a Lot of Weight

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    Imagine an older man goes in to see his doctor. He’s 72 years old and moderately overweight: 5-foot-10, 190 pounds. His blood tests show high levels of triglycerides. Given his BMI—27.3—the man qualifies for taking semaglutide or tirzepatide, two of the wildly popular injectable drugs for diabetes and obesity that have produced dramatic weight loss in clinical trials. So he asks for a prescription, because his 50th college reunion is approaching and he’d like to get back to his freshman-year weight.

    He certainly could use these drugs to lose weight, says Thomas Wadden, a clinical psychologist and obesity researcher at the University of Pennsylvania, who recently laid out this hypothetical in an academic paper. But should he? And what about the tens of millions of Americans 65 and older who aren’t simply trying to slim down for a cocktail party, but live with diagnosable obesity? Should they be on Wegovy or Zepbound?

    Already, seniors make up 26.6 percent of the people who have been prescribed these and other GLP-1 agonists, including Ozempic, since 2018, according to a report from Truveta, which draws data from a large network of health-care systems. In the coming years, that proportion could rise even higher: The bipartisan Treat and Reduce Obesity Act, introduced in Congress last July, would allow Medicare to cover drug treatments for obesity among its roughly 50 million Part D enrollees above the age of 65; in principle, about two-fifths of that number would qualify as patients. Even if this law doesn’t pass (and it’s been introduced half a dozen times since 2012), America’s retirees will continue to be prescribed these drugs for diabetes in enormous numbers, and they’ll be losing weight on them as well. One way or another, the Boomers will be giving shape to our Ozempic Age.

    Economists say the cost to Medicare of giving new drugs for obesity to just a fraction of this aging generation would be staggering—$13.6 billion a year, according to an estimate published in The New England Journal of Medicine last March. But the health effects of such a program might also be unsettling. Until recently, the very notion of prescribing any form of weight loss whatsoever to an elderly patient—i.e., someone 65 or older—was considered suspect, even dangerous. “Advising weight loss in obese older adults is still shunned in the medical community,” the geriatric endocrinologist Dennis Villareal and his co-authors wrote in a 2013 “review of the controversy” for a medical journal. More than a decade later, clinicians are still struggling to reach consensus on safety, Villareal told me.

    Ample research shows that interventions for seniors with obesity can resolve associated complications. Wadden helped run a years-long, randomized trial of dramatic calorie reduction—using liquid meal replacements, in part—and stringent exercise advice for thousands of overweight adults with type 2 diabetes. “Clearly the people who were older did have benefits in terms of improved glycemic control and blood-pressure control,” he told me. Other, smaller studies led by Villareal find that older people who succeed at losing weight through diet and exercise end up feeling more robust.

    Such outcomes are significant on their own terms, says John Batsis, who treats and studies geriatric obesity at the UNC School of Medicine. “When we talk about older adults, we really need to be thinking about what’s important to older adults,” he told me. “It’s for them to be able to get on the floor and play with their grandchildren, or to be able to walk down the hallway without being completely exhausted.” But weight loss can also have adverse effects. When a person addresses their obesity through dieting alone, as much as 25 percent of the weight they lose derives from loss of muscle, bone, and other fat-free tissue. For seniors who, through natural aging, are already near the threshold of developing a functional impairment, a sudden drop like this could be enfeebling. Wadden’s trial found that, among the people who were on the weight-loss program for more than a decade, their risk of fracture to the hip, shoulder, upper arm, or pelvis increased by 39 percent. An analogous increase has turned up in studies of patients who undergo bariatric surgery, Batsis told me.

    Read: Ozempic makes you lose more than fat

    The effect of dieting on muscle and bone can be attenuated, but not prevented, through resistance training. And obesity itself—which is associated with higher bone density, but perhaps also reduced bone quality—may pose its own fracture risks, Batsis said. But even when a weight-loss treatment benefits an older patient, what happens when it ends? People tend to regain fat, but they don’t recover bone and muscle, Debra Waters, the director of gerontology research at the University of Otago, in New Zealand, told me. That makes the long-term effects of these interventions for older adults very murky. “What happens when they’re 80? Are they going to have really poor bone quality, and be at higher risk of fracture? We don’t know,” Waters said. “It’s a pretty big gamble to take, in my opinion.”

    Villareal told me that doctors should apply “the general principle of starting slow and going slow” when their older patients are trying to lose weight. But that approach doesn’t necessarily square with the rapid and remarkable weight loss seen in patients who are taking semaglutide or tirzepatide, which may produce a greater proportional loss of muscle and bone. (For semaglutide, it appears to be about 40 percent.)

    Then again, when given to laboratory animals, GLP-1 drugs seem to tamp down inflammation in the brain; and they’re now in clinical trials to see whether they might slow the progression of Alzheimer’s disease and dementia. Their multiple established benefits could also help seniors address several chronic problems—diabetes, obesity, fatty liver disease, and kidney disease, for instance—all at once. “Such a ‘one-stop shop’ approach can lead to reduction of medication burden, adverse drug events, hypoglycemic episodes, medication costs, and treatment nonadherence,” one team of geriatricians proposed in 2019.

    Overall, Batsis remains optimistic. “As a clinician, I’m very excited about these medications,” he told me. As a scientist, though, he’s inclined to wait and see. It’s surely true that some degree of weight loss is a great idea for some older patients. “But the million-dollar question is: What’s the sweet spot? How much weight is really enough? Is it 5 to 10 percent? Or is it 25 percent? We don’t know.” Waters said that if Medicare is going to pay for people’s Wegovy, then it should also cover scans of their body composition, to help predict how weight loss might affect their muscles and bones. Wadden said he thinks that treatments should be limited to people who have specific, weight-related complications. For everyone else—as for the hypothetical 72-year-old man who is prepping for his college reunion—he counsels prudence.

    To some extent, such advice is beside the point. Older people are already on Ozempic, and they’re already on Trulicity, and some of them are already taking GLP-1 drugs as a treatment for obesity. Truveta reported that the patients in its member health-care systems who are over 65 have received 281,000 prescriptions for GLP-1 drugs across the past five years. Given the network’s size, one can assume that at least 1 million seniors, overall, have already tried these medications. Millions more will try them in the years to come. If we still have questions about their use, mass experience will start providing answers.

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    Daniel Engber

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  • A Gaping Hole in Cancer-Therapy Trials

    A Gaping Hole in Cancer-Therapy Trials

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    This article was originally published by Undark Magazine.

    In October 2021, 84-year-old Jim Yeldell was diagnosed with Stage 3 lung cancer. The first drug he tried disrupted his balance and coordination, so his doctor halved the dose to minimize these side effects, Yeldell recalls. In addition, his physician recommended a course of treatment that included chemotherapy, radiation, and a drug targeting a specific genetic mutation. This combination can be extremely effective—at least in younger people—but it can also be “incredibly toxic” in older, frail people, says Elizabeth Kvale, a palliative-care specialist at Baylor College of Medicine, and also Yeldell’s daughter-in-law.

    Older patients are often underrepresented in clinical trials of new cancer treatments, including the one offered to Yeldell. As a result, he only learned of the potential for toxicity because his daughter-in-law had witnessed the treatment’s severe side effects in the older adults at her clinic.

    This dearth of age-specific data has profound implications for clinical care, because older adults are more likely than younger people to be diagnosed with cancer. In the U.S., approximately 42 percent of people with cancer are over the age of 70—a number that could grow in the years to come—yet they comprise less than a quarter of the people in clinical trials to test new cancer treatments. Many of those who do participate are the healthiest of the aged, who may not have common age-related conditions like diabetes or poor kidney or heart function, says Mina Sedrak, a medical oncologist and the deputy director of the Center for Cancer and Aging at City of Hope National Medical Center.

    For decades, clinical trials have tended to exclude older participants for reasons that include concerns about preexisting conditions and other medications and participants’ ability to travel to trial locations. As a result, clinicians cannot be as certain that approved cancer drugs will work as predicted in clinical trials for the people most likely to have cancer. This dearth of data means that older cancer patients must decide if they want to pursue a treatment that might yield fewer benefits—and cause more side effects—than it did for younger people in the clinical trial.

    This evidence gap extends across the spectrum of cancer treatments—from chemotherapy and radiation to immune-checkpoint inhibitors—with sometimes-dire results. Many forms of chemotherapy, for example, have proved to be more toxic in older adults, a discovery that came only after the drugs were approved for use in this population. “This is a huge problem,” Sedrak says. In an effort to minimize side effects, doctors will often tweak the dose or duration of medications that are given to older adults, but these physicians are doing this without any real guidance.

    Despite recommendations from funders and regulators, as well as extensive media coverage, not much has changed in the past three decades. “We’re in this space where everyone agrees this is a problem, but there’s very little guidance on how to do better for older adults,” Kvale says. “The consequences in the real world are stark.”

    Post-approval studies of cancer drugs have helped shed light on the disconnect between how these drugs are used in clinical trials and how they are used in clinics around the country.

    Read: America’s most popular drug has a puzzling side effect. We finally know why.

    For example, when Cary Gross, a physician and cancer researcher at Yale, set out to study the use of a new kind of cancer drug known as an immune-checkpoint inhibitor, he knew that most clinicians were well aware that clinical trials overlooked older patients. Gross’s research team suspected that some doctors might be wary of offering older adults the treatments, which work by preventing immune cells from switching off, thus allowing them to kill cancer cells. “Maybe they’re going to be more careful,” he says, and offer the intervention to younger patients first.

    But in a 2018 analysis of more than 3,000 patients, Gross and his colleagues found that within four months of approval by the FDA, most patients eligible to receive a class of immune-checkpoint inhibitors were being prescribed the drugs. And the patients receiving this treatment in clinics were significantly older than those in the clinical trials. “Oncologists were very ready to give these drugs to the older patients, even though they’re not as well represented,” Gross says.

    In another analysis, published this year, Gross and his colleagues examined how these drugs helped people diagnosed with certain types of lung cancer. The team found that the drugs extended the life of patients under the age of 55 by a median of four and a half months, but only by a month in those over the age of 75.

    The evidence doesn’t suggest that checkpoint inhibitors aren’t helpful for many patients, Gross says. But it’s important to identify which particular populations are helped the most by these drugs. “I thought that we would see a greater survival benefit than we did,” he says. “It really calls into question how we’re doing research, and we really have to double down on doing more research that includes older patients.”

    People over the age of 65 don’t fare well with other types of cancer treatments either. About half of older patients with advanced cancer experience severe and even potentially life-threatening side effects with chemotherapy, which can lead oncologists to lower medication doses, as in Yeldell’s case.

    There’s a strong connection between the lack of evidence from clinical trials and worse outcomes in the clinic, according to Kvale. “There’s a lot of enthusiasm for these medicines that don’t seem so toxic up front,” she says, “but understanding where they do or don’t work well is key—not just because of the efficacy, but because those drugs are almost toxically expensive sometimes.”

    Since the earliest reports of this data gap, regulators and researchers have tried to fix the problem. Changes to clinical trials have, in principle, made it easier for older adults to sign up. For instance, fewer and fewer studies have an upper age limit for participants. Last year, the FDA issued guidance to industry-funded trials recommending the inclusion of older adults and relaxing other criteria, to allow for participants with natural age-related declines. Still, the problem persists.

    When Sedrak and his colleagues set out to understand why the needle had moved so little over the past few decades, their analysis found a number of explanations, beginning with eligibility criteria that may inadvertently disqualify older adults. Physicians may also be concerned about their older patients’ ability to tolerate unknown side effects of new drugs. Patients and caregivers share these concerns. The logistics of participation can also prove problematic.

    “But of all these, the main driving force, the upstream force, is that trials are not designed with older adults in mind,” Sedrak says. Clinical trials tend to focus on survival, and although older adults do care about this, many of them have other motivations—and concerns—when considering treatment.

    Clinical trials are generally geared toward measuring improvements in health: They may track the size of tumors or months of life gained. These issues aren’t always top of mind for older adults, according to Sedrak. He says he’s more likely to hear questions about how side effects may influence the patient’s cognitive function, ability to live independently, and more. “We don’t design trials that capture the end points that older adults want to know,” he says.

    Read: Hiccups have a curious connection to cancer

    As a group, older adults do experience more side effects, sometimes so severe that the cure rivals the disease. In the absence of evidence from clinical trials, clinicians and patients have tried to find other ways to predict how a patient’s age might influence their response to treatment. In Yeldell’s case, discussions with Kvale and his care team led him to choose a less intensive course of treatment that has kept his cancer stable since October 2022. He continues to live in his own home and exercises with a trainer three times a week.

    For others trying to weigh their choices, researchers are developing tools that can create a more complete picture by accounting for a person’s physiological age. In a 2021 clinical trial, Supriya Mohile, a geriatric oncologist at the University of Rochester, and her colleagues tested the use of one such tool, known as a geriatric assessment, on the side effects and toxicity of cancer treatments. The tool assesses a person’s biological age based on various physiological tests.

    The team recruited more than 700 people with an average age of 77 who were about to embark on a new cancer-treatment regimen with a high risk of toxicity. Roughly half of the participants received guided treatment-management recommendations based on a geriatric assessment, which their oncologists factored into their treatment decisions. Only half of this group of patients experienced serious side effects from chemotherapy, compared with 71 percent of those who didn’t receive specialized treatment recommendations.

    This type of assessment can help avoid both undertreatment of people who might benefit from chemotherapy and overtreatment of those at risk of serious side effects, Mohile says. It doesn’t compensate for the lack of data on older adults. But in the absence of that evidence, tools such as geriatric assessment can help clinicians, patients, and families make better-informed choices. “We’re kind of going backwards around the problem,” Mohile says. Although geriatric oncologists recognize the need for better ways to make decisions, she says, “I think the geriatric assessment needs to be implemented until we have better clinical-trial data.”

    Since 2018, the American Society of Clinical Oncology has recommended the use of geriatric assessment to guide cancer care for older patients. But clinicians have been slow to follow through in their practice, in part because the assessment doesn’t necessarily show any cancer-specific benefits, such as tumors shrinking and people living longer. Instead, the tool’s main purpose is to improve quality of life. “We need more prospective therapeutic trials in older adults, but we also need all of these other mechanisms to be funded,” Mohile says, “So we actually know what to do for older adults who are in the real world.”

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    Jyoti Madhusoodanan

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  • The FDA’s New ‘Don’t Say Gay’ Policy for Blood Donation

    The FDA’s New ‘Don’t Say Gay’ Policy for Blood Donation

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    For decades now, gay men have been barred from giving blood. In 2015, what had been a lifetime ban was loosened, such that gay men could be donors if they’d abstained from sex for at least a year. This was later shortened to three months. Last week, the FDA put out a new and more inclusive plan: Sexually active gay and bisexual people would be permitted to donate so long as they have not recently engaged in anal sex with new or multiple partners. Assistant Secretary for Health Rachel Levine, the first Senate-confirmed transgender official in the U.S., issued a statement commending the proposal for “advancing equity.” It “treats everyone the same,” she said, “regardless of gender and sexual orientation.”

    As a member of the small but honorable league of gay pathologists, I’m affected by these proposed policy changes more than most Americans. I’m subject to restrictions on giving blood, and I’ve also been responsible for monitoring the complications that can arise from transfusions of infected blood. I am quite concerned about HIV, given that men who have sex with men are at much greater risk of contracting the virus than members of other groups. But it’s not the blood-borne illness that I, as a doctor, fear most. Common bacteria lead to far more transfusion-transmitted infections in the U.S. than any virus does, and most of those produce severe or fatal illness. The risk from viruses is extraordinarily low—there hasn’t been a single reported case of transfusion-associated HIV in the U.S. since 2008—because laboratories now use highly accurate tests to screen all donors and ensure the safety of our blood supply. This testing is so accurate that preventing anyone from donating based on their sexual behavior is no longer logical. Meanwhile, new dictates about anal sex, like older ones explicitly targeting men who have sex with men, still discriminate against the queer community—the FDA is simply struggling to find the most socially acceptable way to pursue a policy that it should have abandoned long ago.

    Strict precautions made more sense 30 years ago, when screening didn’t work nearly as well as it does today. Patients with hemophilia, many of whom rely on blood products to live, were prominent, early victims of our inability to keep HIV out of the blood supply. One patient who’d acquired the virus through a transfusion lamented to The New York Times in 1993 that he had already watched an uncle and a cousin die of AIDS. Those days of “shock and denial,” as the Times described it, are thankfully behind us. But for older patients, memories of the crisis in the ’80s and early ’90s linger, and cause significant anxiety. Even people unaware of this historical context may consider the receipt of someone else’s blood disturbing, threatening, or sinful.

    As a doctor, I’ve found that patients tend to be more hesitant about getting a blood transfusion than they are about taking a pill. I’ve had them ask for a detailed medical history of the donor, or say they’re willing to take blood only from a close relative. (Typically, neither of these requests can be fulfilled for reasons of privacy and practicality.) Yet the same patients may accept—without question—drugs that carry a risk of serious complication that is thousands of times higher than the risk of receiving infected blood. Even when it comes to blood-borne infections, patients seem to worry less about the greatest danger—bacterial contamination—than they do about the transfer of viruses such as HIV and hepatitis C. I can’t fault anyone for being sick and scared, but the risk of contracting HIV from a blood transfusion is not just low—it’s essentially nonexistent.

    Read: Blood plasma, sweat, and tears

    Donors’ feelings matter, too, and the FDA’s policies toward gay and bisexual men who wish to give blood have been unfair for many years. While officials speak in the supposedly objective language of risk and safety, their selective deployment of concern suggests a deeper homophobia. As one scholar put it in The American Journal of Bioethics more than a decade ago, “Discrimination resides not in the risk itself but in the FDA response to the risk.” Many demographic groups are at elevated risk of contracting HIV, yet the agency isn’t continually refining its exclusion criteria for young people or urban dwellers or Black and Hispanic people. Federal policy did prohibit Haitians from donating blood from 1983 to 1991, but activists successfully lobbied for the reversal of this ban with the powerful slogan “The H in HIV stands for human, not Haitian.” Nearly everyone today would find the idea of rejecting blood from one racial group to be morally repugnant. Under its new proposal, which purports to target anal sex instead of homosexuality itself, the FDA effectively persists in rejecting blood from sexual minorities.

    The planned update would certainly be an improvement. It comes out of years of advocacy by LGBTQ-rights organizations, and its details are apparently supported by newly conducted government research. Peter Marks, the director of the Center for Biologics Evaluation and Research at the FDA, cited an unpublished study showing that “a significant fraction” of men who have sex with men would now be able to donate. But the plan is still likely to exclude a large portion of them—even those who wear condoms or regularly test for sexually transmitted infections. An FDA spokesperson told me via email that “additional data are needed to determine what proportion of [men who have sex with men] would be able to donate under the proposed change.”

    Research done in France, Canada, and the U.K., where similar policies have since been adopted over the past two years, demonstrates the risk. A French blood-donation study, for instance, estimated that 70 percent of men who have sex with men had more than one recent partner; and when Canadian researchers surveyed queer communities in Montreal, Toronto, and Vancouver, they found that up to 63 percent would not be eligible to donate because they’d recently had anal sex with new or multiple partners. Just 1 percent of previously eligible donors would have been rejected by similar criteria. The U.K. assumed in its calculations that 35 to 50 percent of men who have sex with men would be ineligible under a policy much like the FDA’s, while only 1.4 percent of previous donors would be newly deferred. If the new rule’s net effect is that gay and bisexual men are turned away from blood centers at many times the rate of heterosexual individuals, what else can you call it but discrimination? The U.S. guidance is supposed to ban a lifestyle choice rather than an identity, but the implication is that too many queer men have chosen wrong. The FDA spokesperson told me, “Anal sex with more than one sexual partner has a significantly greater risk of HIV infection when compared to other sexual exposures, including oral sex or penile-vaginal sex.”

    If the FDA wants to pry into my sex life, it should have a good reason for doing so. The increasing granularity and intimacy of these policies—specifying numbers of partners, kinds of sex—gives the impression that the stakes are very high: If we don’t keep out the most dangerous donors, the blood supply could be ruined. But donor-screening questions are a crude tool for picking needles from a haystack. The only HIV infections that are likely to get missed by modern testing are those contracted within the previous week or two. This suggests that, at most, a couple thousand individuals—gay and straight—across the entire country are at risk of slipping past our testing defenses at any given time. Of course, very few of them will happen to donate blood right then. No voluntary questionnaire can ever totally exclude this possibility, but patients and doctors already accept other life-threatening transfusion risks that occur at much greater rates than HIV transmission ever could. When I would be on call for monitoring transfusion reactions at a single hospital, the phone would ring a few times every night. Yet blood has been given out tens of millions of times across the country since the last known instance of a transfusion resulting in a case of HIV.

    Read: How blood-plasma companies target the poorest Americans

    Early data suggest that the overall risk-benefit calculus of receiving blood isn’t likely to change. When eligibility criteria were first relaxed in the U.S. a few years ago, the already tiny rate of HIV-positive donations remained minuscule. Real-world results from other countries that have recently adopted sexual-orientation-neutral policies will become available in the coming years. But modeling studies already support removing any screening question that explicitly or implicitly targets queer men. A 2022 Canadian analysis suggested that removing all questions about men who have sex with men would not result in a significantly higher risk to patients. “Extra behavioral risk questions may not be necessary,” the researchers concluded. If there must be a restriction in place, then one narrowly tailored to the slim risk window of seven to 10 days before donation should be good enough. (The FDA says that its proposed policy “would be expected to reduce the likelihood of donations by individuals with new or recent HIV infection who may be in the window period.”)

    As a gay man, I realize that, brief periods of crisis during the coronavirus pandemic aside, no one needs my blood. Only 6.8 percent of men in the U.S. identify as gay or bisexual, so our potential benefit to the overall supply is inherently modest. If we went back to being banned completely, patients would not be harmed. But reversing that ban, both in letter and in spirit, would send a vital message: Our government and health-care system view sexual minorities as more than a disease vector. A policy that uses anal sex as a stand-in for men who have sex with men only further stigmatizes this population by impugning one of its main sources of sexual pleasure. There is no question that nonmonogamous queer men have a greater chance of contracting HIV. But a policy that truly treats everyone the same would accept a tiny amount of risk as the price of working with human beings.

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    Benjamin Mazer

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