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Tag: GLP-1s

  • Semaglutide Helps Your Heart Even If the Scale Doesn’t Budge, Study Shows

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    The benefits of semaglutide, the active ingredient in popular drugs Ozempic and Wegovy, aren’t just limited to treating obesity. New research shows that semaglutide can protect people’s hearts regardless of how many pounds they lose while taking it.

    Scientists examined data from a large-scale clinical trial of people with obesity and pre-existing cardiovascular disease. Compared to people on placebo, they found, those on semaglutide were less likely to develop heart attacks and other cardiovascular problems—even when people hadn’t lost much weight at all. The results indicate that semaglutide can improve heart health in more than one way, the researchers and outside experts say.

    The findings “highlight that the cardioprotective effects of semaglutide may be independent of adiposity and weight loss,” Laurence Sperling, a preventive cardiologist at Emory University not affiliated with the study, told Gizmodo.

    Good for the heart

    Semaglutide and other GLP-1 drugs have heralded a new era of obesity (and diabetes) treatment. But for a time, it was unclear if these drugs would also improve people’s cardiovascular health, and to what extent.

    Novo Nordisk (the makers of Ozempic and Wegovy) funded a large, randomized, controlled, and double-blinded study designed to answer that open question—the SELECT trial. It involved roughly 17,000 people with obesity and a history of cardiovascular disease, who were followed for up to five years. The primary results from the SELECT trial, published almost two years ago, showed that high-dose semaglutide (the version approved as Wegovy for treating obesity) reduced people’s risk of heart attacks and other major cardiovascular events by 20% during the study period. Based on these findings, the Food and Drug Administration expanded its approval of Wegovy to also cover the prevention of cardiovascular disease in high-risk groups.

    Since obesity is known to increase the risk of heart disease, it’s easy to assume that semaglutide’s heart benefits are mostly tied to helping people lose weight. But some evidence has already suggested it’s more complicated than that. In this new research, some of the researchers who conducted the SELECT trial took a closer look at their data.

    They ultimately found no clear relationship between how much weight someone had lost early into the study (20 weeks in) and their reduced risk of cardiovascular disease. The heart-protective benefits of semaglutide were also largely the same across different baseline weight groups. In other words, someone who was overweight (a body mass index between 27 and 30) at the start of the study tended to see a similar reduction in heart disease risk as compared to someone with the highest level of obesity (a BMI over 40).

    “This gives us important information that maybe we should be looking at the indication for these drugs beyond just whether your BMI is more than 27,” Howard Weintraub, preventive cardiologist and clinical director at the Center for the Prevention of Cardiovascular Disease at NYU Langone Heart, told Gizmodo. Weintraub was one of the lead researchers of the original SELECT trial but wasn’t involved in the new research.

    The study did see an association between someone’s waist circumference throughout the study and heart disease risk. The more a person’s waist shrunk, for instance, the greater reduction in risk they had. Waist circumference is another measure of excess body fat. So semaglutide’s slimming of body fat does seem to help explain why it prevents heart disease—but only partly. The researchers estimated that just a third of semaglutide’s effect on lowering cardiovascular disease could be accounted for by a trimming waistline.

    The team’s findings were published Tuesday in The Lancet.

    Beyond weight loss

    The authors say these findings could have far-reaching implications for how semaglutide and similar GLP-1 drugs should be used. If its heart benefits are largely independent of weight loss, then it wouldn’t be helpful to limit the prescribing of these drugs based solely on BMI. People taking semaglutide who lose enough weight to no longer qualify as obese might still benefit from continuing the drug for its heart-protective effects—just as those who don’t lose much weight may, too.

    It’s even possible that GLP-1 therapy could one day be reframed as a standalone treatment for heart disease, regardless of BMI. Richard Kovacs, the interim chief of cardiovascular medicine at Indiana University’s School of Medicine, who is not involved with the study, notes that these findings could shape future guidelines in how doctors manage cardiovascular disease.

    “This is a potential guideline changer because of its robust effect here. This is a well-run, large trial that we’re all familiar with. It’s an important analysis of it,” Kovacs, who is also the chief medical officer for the American College of Cardiology, told Gizmodo. At the same time, he adds, it would probably still take more data from at least one other large randomized trial for such a change to happen easily.

    One important question left to answer is exactly how these drugs can improve our heart health. The researchers argue that some of the drug’s protection likely stems from its anti-inflammatory effects, both on excess body fat and elsewhere. But the drug’s influence on blood sugar control or our blood vessels could also be playing a part.

    Yet another question is whether these heart-bolstering effects can be seen in people who aren’t overweight or obese—something that Kovacs suspects will be put to the test soon enough. And it’s still important to study whether similar benefits are apparent with other GLP-1 medications, including newer drugs that are combining GLP-1s with other compounds.

    For now, this research is continuing to demonstrate that there’s still so much left to learn about these already game-changing drugs.

    “I don’t think we know everything that the GLP-1 agonists do yet,” Weintraub said. “So doctors will need to look at this beyond the prism of a TikTok video, where kids are looking to lose a couple of pounds to look better. That may certainly happen, but I think the cosmetic issues and the role of weight loss are just a small part of it. And as a cardiologist, I’m more motivated by the sort of findings we’re seeing here in reducing cardiovascular disease.”

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    Ed Cara

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  • Weight-inclusive care company, knownwell, opens first Atlanta clinic

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    Located in Sandy Springs, this new location marks the company’s seventh opening in the last year, bringing its physical presence to 10 total clinics across the U.S., in addition to virtual care nationwide. Photo by Isaiah Singleton/The Atlanta Voice

    knownwell, the first-of-its-kind weight-inclusive primary care and metabolic health company, officially unveiled the physical expansion of its care offering to the metro Atlanta area.

    Located in Sandy Springs, this new location marks the company’s seventh opening in the last year. It brings the company’s physical presence to 10 clinics across the U.S., in addition to virtual care nationwide. 

    Coming on the heels of knownwell’s most recent opening last month in Woburn, Massachusetts, the new Atlanta location will continue to advance the company’s mission to deliver care, free of bias and shame, for individuals affected by overweight or obesity. 

    The obesity crisis in America continues to worsen, with one in five U.S. adults experiencing obesity. Few options exist for those seeking a healthcare home.

    Offering comprehensive metabolic health services, including the prescription of GLP-1s, nutrition, and behavioral counseling, knownwell’s goal is not solely to help patients lose weight, but to provide a space where their health problems are not dismissed or written off because of their weight. 

    knownwell, the first-of-its-kind weight-inclusive primary care and metabolic health company, officially unveiled the physical expansion of its care offering to the metro Atlanta area. Photo by Isaiah Singleton/The Atlanta Voice

    Having struggled with obesity since childhood, Brooke Boyarksy Pratt, CEO and co-founder of knownwell, says she is extremely passionate about bringing inclusive care to communities across the U.S.

    “Georgia has one of the highest obesity rates in America, yet few options for obesity-focused health services exist, leaving its residents underserved and without access to the comprehensive, compassionate care they deserve,” she said. “knownwell’s arrival in Atlanta is the next step in our nationwide expansion and continued goal to reach more lives across the U.S.”

    The importance of bringing the clinic to Atlanta, Pratt says, is for patients with overweight and obesity conditions who are looking for thoughtful, comprehensive health care.

    “We take Medicare, Medicaid, and other commercial insurance. We’re super accessible,” she said.

    Pratt also said many patients avoid care because of their size as well which another reason they wanted to expand to other markets.

    “We’ve made the clinic that’s literally and physically comfortable for patients, regardless of their body size,” she said. “There’s interesting research that suggests that it’s not just about the doctor, but also how they are treated by the front desk or in the billing department

    As for services, knownwell offers two primary things, which is inclusive primary care and specific metabolic care. The primary care, she describes, is thoughtful and accepts patients as they are and includes normal primary care such as physicals, preventive screenings, and virtual care.

    Metabolic care, she says, offers patients ways to lose weight, manage diabetes, and focusing on managing hypertension.

    “With those patients, we help them with those wellness goals,” she said.

    Atlanta Market Development Lead Clinician Ijeoma Azonobi says she is thrilled to bring the knownwell model of care to Atlanta, a model that puts the patients at the center, offering compassion, respect, and evidence-based treatment.

     “Our community deserves healthcare that makes them feel seen and supported, while addressing the full spectrum of their health needs, not just a number on the scale. I am excited to make that a reality here,” she said.

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    Isaiah Singleton

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  • Ozempic Can Turn Into No-zempic

    Ozempic Can Turn Into No-zempic

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    No medication in the history of modern weight loss has inspired as much awe as the latest class of obesity drugs. Wegovy and Zepbound are so effective that they are often likened to “magic” and “miracles.” Indeed, the weekly injections, which belong to a broader class known as GLP-1s, can lead to weight loss of 20 percent or more, fueling hype about a future in which many more millions of Americans take them. Major food companies including Nestlé and Conagra are considering tailoring their products to suit GLP-1 users. Underlying all this excitement is a huge assumption: They work for everyone.

    But for a lot of people, they just don’t. Anita, who lives in Arizona, told me she “took it for granted” that she would lose weight on a GLP-1 drug because “the people around me who were on it were just dropping weight like mad.” Instead, she didn’t shed any pounds. Likewise, Kathryn, from Florida, hasn’t lost any weight since starting the medication in October. “I was really hoping this was something that would be a game changer for me, but it feels like it was just a lot of wasted money,” she told me. (I’m identifying both Anita and Kathryn by their first name only to allow them to speak openly about their health issues.)

    Some people can’t tolerate the side effects of the drugs and have to stop taking them. Others simply don’t respond. For some, the strength of the dose, or length of the treatment, does not seem to make a difference. Appetites might remain robust; the “food chatter” in the brain may stay noisy. Together, both groups of less successful GLP-1 users account for a not-insignificant share of patients on these drugs—potentially up to a third. “We don’t really know why it happens, [but] we know it does happen,” Louis Aronne, an obesity-medicine specialist at Weill Cornell Medical College, told me. Despite the promise of a so-called Ozempic revolution, lots of “No-zempics” have been left behind.

    Of the two biggest reasons some people don’t lose weight on GLP-1 drugs—side effects and nonresponse—the former is much more straightforward. The GLP-1 drugs Wegovy and Zepbound (which contain the active ingredients semaglutide and tirzepatide, respectively), are known for causing potentially gnarly gastrointestinal symptoms, such as nausea and vomiting, although most people’s reactions are mild and temporary. Yet some have it far worse. Severe, albeit uncommon, side effects include pancreatitis, severe gastrointestinal distress, low blood sugar, and even hair loss, which “can push people off” the drugs, Steven Heymsfield, a professor who studies obesity at Louisiana State University, told me. In one of the biggest studies of semaglutide, encompassing more than 17,000 people over about five years, nearly 17 percent of patients discontinued the medication because of side effects.

    Far more mysterious are the people who tolerate the drugs but respond weakly to them—or sometimes not at all. Researchers have known this might happen since these drugs were in early clinical trials. About 14 percent of people who took semaglutide for obesity saw minimal impacts of less than 5 percent weight loss in one study, as did 9 to 15 percent of people who took tirzepatide in a similar one. In her own experience working with patients, “somewhere between a quarter and a third” are nonresponders, Fatima Cody Stanford, an obesity-medicine specialist at Harvard, told me, adding that it can take up to three months to determine whether the drug is working or not. That the same medication at the same dosage can lead to dramatic weight loss in one person and hardly any in another “remains confounding,” Aronne told me.

    The broad explanation is that it has something to do with genetics. The drugs work by masquerading as the appetite-suppressing hormone GLP-1 and binding to its receptor, like a key fitting into a lock. Although the lock’s overall shape is generally consistent from person to person, its nooks and crannies can vary because of genetic differences. “For some people, that key just won’t fit right,” Eduardo Grunvald, an obesity-medicine doctor at UC San Diego Health, told me. In other cases, genes may limit the effects of these drugs after they bind to GLP-1 receptors. One possibility is that people metabolize the drugs differently: Some patients may break them down too quickly for them to take effect; others may process them too slowly, potentially building up such high levels of the medications that they become toxic, Heymsfield said.

    For No-zempic patients, perhaps the most consequential impact of individual variation is on the propensity for obesity itself. “We are all very different from a genetic standpoint, in terms of our risk of weight gain,” Grunvald said. Numerous factors can drive obesity, including diet, environment, stress, and—most pertinent to GLP-1 drugs—altered brain function.

    GLP-1 drugs target a pathway that regulates appetite and insulin levels. Some cases of obesity can be caused by a disruption in that particular mechanism, in which case GLP-1s can indeed be wondrous. But “not everyone has dysfunction in this particular pathway,” Stanford said. When that is the case, the drugs won’t be very effective. A different pathway, for example, controls the absorption of fat from food; another increases energy expenditure. In these people, GLP-1s might tamp down appetite to a degree, maybe leading to some weight loss, but a different drug may be required to treat obesity at its root. “It is not all about food intake,” Stanford said.

    That’s not to say that No-zempics are out of options. They might have better success switching from one GLP-1 to the other, or even stacking them, Heymsfield said. Some patients who don’t respond to GLP-1s at all can get better results with older drugs that work on different obesity pathways, Aronne said. One, called Qysmia, a combination of the decades-old drugs phentermine and topiramate, can lead to an average weight loss of 14 percent body weight at its highest dose. If medications don’t work, bariatric surgery remains a powerful option, one that may even be growing in popularity. Last year, the number of bariatric surgeries performed in the U.S. grew despite the boom in GLP-1 usage, a trend that some expect to continue, because so many people don’t tolerate the drugs.

    The intense hype around the game-changing nature of GLP-1s makes it easy to forget that they are, in fact, just drugs. “Every drug that’s ever been made” works in some people and not in others, Heymsfield said; there’s no reason to think GLP-1s would be any different. Remembering that they are in an early stage of development has a sobering effect. Eventually, obesity drugs may leave fewer people behind. The category is expanding rapidly: By one count, more than 90 new drug candidates are in development.

    They are evolving to attack obesity from multiple fronts, which, at least in theory, widens their net of potential users. In an early study on an experimental candidate named retatrutide—called a triple agonist because it acts on GLP-1 as well as two other targets involved in obesity, GIP and glucagon receptors—100 percent of people on the highest dose lost 5 percent or more of their body weight. New candidates are also expected to have fewer side effects. They have to, Heymsfield said, because the competition is so steep that any new drug has to be “as good with less side effects, or better.”

    But no matter how good these drugs get, it’s unrealistic to think that they’ll become a one-size-fits-all treatment for everyone with obesity. The disease is simply too complex, with too many drivers, for a single type of medication to treat it. More than 200 different drugs exist for treating high blood pressure alone; in comparison, Aronne said, regulating weight is “far more complicated.” The future, rife with options, holds promise that No-zempics may find a way forward. Yet considering all the unknowns about obesity and what causes it, that may not be enough to guarantee that they will see the results they want.

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    Yasmin Tayag

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