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Tag: GLP-1 receptor agonist

  • Next Gen Weight Loss Drugs Are Coming for Ozempic’s Throne

    Next Gen Weight Loss Drugs Are Coming for Ozempic’s Throne

    The future of weight loss is fast approaching. At a recent scientific conference, drug companies showed off a variety of next-generation drugs for both obesity and type 2 diabetes. Some of these treatments might help people lose even more weight than current forerunners like Novo Nordisk’s semaglutide—the active ingredient in popular drugs Ozempic and Wegovy—while others may come with fewer side effects or be easier to take.

    Semaglutide is a drug that mimics GLP-1, one of several hormones that help regulate our sense of hunger and blood sugar. In clinical trials, semaglutide has proven to be much more effective at treating obesity than diet and exercise alone. Previously only approved for type 2 diabetes as Ozempic, semaglutide was approved for obesity in 2021 under the name Wegovy. However, it’s already started to be overshadowed by the arrival of Eli Lilly’s tirzepatide, which combines GLP-1 with another incretin hormone called GIP. Tirzepatide was approved by the Food and Drug Administration in 2021 for type 2 diabetes under the brand name Mounjaro; in November 2023, it was approved to treat obesity as Zepbound.

    Newer treatments in the works are poised to compete with and possibly surpass both of these drugs. The American Diabetes Association held its annual conference over the past weekend, and the emergence of these future medications was a big aspect of the event. Companies presented preliminary data on over two dozen GLP-1 related drugs, all in various stages of development.

    “We’ve heard about Ozempic and Mounjaro and so on, but now we’re seeing lots and lots of different drug candidates in the pipeline, from very early-stage preclinical all the way through late-stage clinical,” Marlon Pragnell, ADA’s vice president of research and science, told NBC News. “It’s very exciting to see so much right now.”

    Altimmune’s pemvidutide, for instance, combines GLP-1 with glucagon, another hormone key to keeping our blood sugar level stable. In Phase II trial data presented this weekend, pemvidutide was found to help people lose over 15% of their baseline weight within 48 weeks, a bit ahead of the pace seen with semaglutide (15% weight loss over 68 weeks). A dual GLP-1/GIP candidate developed by scientists in China, called HRS9531 for now, was found to cause up to 16% weight loss within 24 weeks. Eli Lilly also presented new data on its second-generation drug retatrutide, which combines GLP-1, GIP, and glucagon, finding it improved insulin’s ability to control blood sugar in people with type 2 diabetes. In previous research, retatrutide was found to cause up to 24% weight loss, the highest mark seen yet with these drugs.

    It’s not certain that these or other GLP-1 drugs in development will truly outmatch semaglutide and tirzepatide in terms of weight loss, but they may still have other benefits over them. Pemvidutide was found to cause less lean body mass loss, for instance, possibly due to the addition of glucagon (exercise naturally raises glucagon levels, so the drug could be mimicking some of the positive effects of exercise). Some experts are skeptical that lean body mass loss is a major concern with these drugs. However, it may be important to prevent this in individuals who are more vulnerable to muscle or bone loss, such as older adults.

    It will take years for these newer drugs to reach the public, assuming they continue to succeed in larger trials. Their arrival may not only help people who don’t respond to existing treatments, though, but could also drive down the overall high costs of these medications (without insurance coverage, which is often denied, a month’s supply of semaglutide can reach over $1,000 per month).

    “Over the past few years, we have seen the substantial impact of new research working to solve the dual health crisis we are facing, obesity and diabetes,” said Robert Gabbay, chief scientific and medical officer for the ADA, in a statement from the ADA. “The studies we are seeing presented at this year’s annual meeting show great promise to fuel new solutions and treatment options for patients across the globe living with type 2 diabetes and obesity.”

    Ed Cara

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  • Weight Loss Drug Users Are Giving Up Their Vices

    Weight Loss Drug Users Are Giving Up Their Vices

    Image: Hollie Adams (Reuters)

    It’s not only food CEOs who need to worry about their bottom lines thanks to in-demand weight loss drugs like Ozempic. Big Tobacco and Alcohol have reason to fret, too.

    A new report from Morgan Stanley finds that people using GLP-1 drugs — among them Ozempic, Wegovy, Mounjaro, and Zepbound — reduce their consumption of tobacco and alcohol while taking the medications. GLP-1s are a class of diabetes and weight loss drugs that have recently caught fire (and blown up sales numbers) for their ability to suppress a user’s appetite.

    The investment bank also surveyed about 300 GLP-1 users about their consumption habits while taking the medication. Analysts at the bank have previously cautioned that the growing use of GLP-1s will put some longterm pressure on fast food sales, as users have reported spending less money at restaurants. But their survey also finds that users are reducing their intake of tobacco and alcohol.

    Could weight loss drugs help users smoke or drink less?

    While 40% of survey respondents said they smoked cigarettes at least weekly before starting a GLP-1 treatment, that number fell to 24% after they started the treatment. Meanwhile, weekly e-cigarette usage dropped from 30% of respondents to 16% after they started taking a GLP-1.

    Morgan Stanley found similar results when it asked respondents about their use of alcohol. About 56-62% of alcohol consumers on GLP-1s reported drinking less alcohol since starting the medications, with about 14-18% cutting their alcohol consumption entirely.

    The analysts noted they were “cautious about drawing conclusions” from their survey about the impact of GLP-1 drugs on addictive behaviors. But there has been anecdotal evidence from patients and health care providers that suggests GLP-1s can help users curb their addictions to alcohol and tobacco. While research hasn’t yet proven a causal link between the two, clinical trials are currently underway to better understand the effects of GLP-1’s on alcohol and tobacco consumption.

    In addition, Morgan Stanley anticipates the GLP-1 frenzy isn’t slowing anytime soon. global market for GLP-1 drugs will reach $105 billion by 2030. It also projects these drugs will be adopted by about 31.5 million people in the U.S. (or about 9% of the nation’s population) by 2035.

    This article originally appeared on Quartz.

    Bruce Gil, Quartz

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  • Beware the Ozempic Burp

    Beware the Ozempic Burp

    On the November morning when the sulfur burps began, Derron Borders was welcoming prospective students at the graduate school where he works in New York. Every few minutes, no matter how hard he tried to stop, another foul-smelling cloud escaped his mouth. “Burps that taste and smell like rotten eggs—I think that’s what I typed in Google,” he told me.

    Eventually, Borders learned that his diabetes medication was to blame. Sulfur burps appear to be a somewhat rare side effect of semaglutide, tirzepatide, and other drugs in their class, known as GLP-1 receptor agonists. Over the past several years, these medications have become more popular under the brand names Ozempic, Wegovy, and Mounjaro, as a diabetes treatment and a weight-loss drug. And as prescription numbers rise, a strange and unpleasant side effect has been growing more apparent too.

    GLP-1 receptor agonists are well known to cause gastrointestinal symptoms, including abdominal pain, diarrhea, and vomiting. In clinical trials of semaglutide for weight loss, 44 percent of participants experienced nausea and 31 percent had diarrhea. (The same conditions afflicted only about one-sixth of participants who received a placebo.) Burping, a.k.a. “eructation,” showed up in about 9 percent of those who got the drug, versus less than 1 percent of those who took a placebo. The FDA lists eructation as a possible side effect for semaglutide and tirzepatide alike.

    But I couldn’t find any information in the clinical-trial reports or FDA fact sheets about sulfur burps in particular, and neither Novo Nordisk nor Eli Lilly, the companies that make these drugs, responded to my inquiries. Laura Davisson, the director of medical weight management at West Virginia University Health Sciences, told me that more than 1,000 of her clinic’s patients are currently on a GLP-1 receptor agonist, and about one-fifth experience sulfur burps at first. For all but a handful of these patients, she said, the issue goes away after a few months. Holly Lofton, an obesity-medicine specialist at NYU, guesses that it affects just 2 percent of her patients.

    Experts aren’t sure why taking GLP-1 receptor agonists might lead to having smelly burps, but they have some theories. Davisson proposed that semaglutide boosts the number of bacteria in patients’ digestive tracts that produce hydrogen sulfide, a gas that can be expelled from either end of the digestive tract, and that smells (as Borders found) like rotten eggs. She also noted that the drugs slow down digestion, which could give the stomach more time to break down food and produce gas. In this situation, Lofton told me, the putrid air may escape most readily up through the mouth, because it’s lighter than the liquids and semi-solids that also fill the stomach. “Whatever’s on top will come up,” she said.

    Eating more than usual while on the medications seems to be a common trigger. Davisson said that certain foods, such as dairy, may also lead to more odorous emissions. “Sometimes it’s a matter of trial and error,” she said. “Some tips that we give people are things like: Don’t eat really heavy meals; don’t eat large portions at once; don’t eat right before bed.” In addition to these behavioral approaches, Craig Gluckman, a gastroenterologist at UCLA Health, told me he recommends antacids and anti-gas medications to patients with GLP-1-agonist-related sulfur burps. (Online, apple-cider vinegar is commonly recommended as a fix, but Gluckman said he would not recommend it.)

    The providers I spoke with said that, in general, patients tend to experience sulfur burps when they’re first starting an Ozempic-like drug, or raising their dose. That was the case for Crystal Garcia, an HR administrator in Texas who started taking semaglutide from a compounding pharmacy after her doctor told her she was prediabetic. (Garcia vlogs about her experience with weight-loss drugs.) Three months later, while out to breakfast at a restaurant, Garcia’s family started to complain about a gross and eggy smell. Garcia figured that the smell was coming from the food, but it lingered in the car after the meal. The family wondered whether Garcia’s young son had had an accident. “I was like, it could not be me. There’s no way,” she told me. But when she burped again, she was forced to change her mind.

    Many patients are unaware that sulfur burps are a possible side effect of their medication until they start, well, burping sulfur. For a while, Borders had no idea that his diabetes medicine might be the culprit; when he saw a physician’s assistant to discuss his issue, “Ozempic didn’t even come up,” he said. The side effect is relatively new to physicians. Earlier GLP-1 agonists didn’t seem to produce sulfur burps so frequently, Lofton said. In her practice, the phenomenon wasn’t really apparent until Ozempic hit the American market in 2018, and even then, she learned about it only from her patients. “I’d never heard of sulfur burps before I started prescribing this medicine,” she said.

    Though the sulfur burps are (physically) harmless, some patients do stop taking their diabetes or weight-loss drugs because of them, Lofton told me. But most, including Garcia and Borders, end up sticking with their program. As bad as the side effects may be, patients think the drugs’ benefits are worth it. “I have had a patient say that her burps smelled like poop,” Davisson said. But even then, she did not want to stop the medication.

    Rachel Gutman-Wei

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  • Lowering the Cost of Insulin Could Be Deadly

    Lowering the Cost of Insulin Could Be Deadly

    When I heard that my patient was back in the ICU, my heart sank. But I wasn’t surprised. Her paycheck usually runs short at the end of the month, so her insulin does too. As she stretches her supply, her blood sugar climbs. Soon the insatiable thirst and constant urination follow. And once her keto acids build up, her stomach pains and vomiting start. She always manages to make it to the hospital before the damage reaches her brain and heart. But we both worry that someday, she won’t.

    The Inflation Reduction Act, passed last month, aims to help people like her by lowering the cost of insulin across America. Although efforts to expand protections to privately insured Americans were blocked in the Senate, Democrats succeeded in capping expenses for the drug among Americans on Medicare at $35 a month, offering meaningful savings for our seniors, some of whom will save hundreds of dollars a month thanks to the measure. In theory, the policy (and similar ones at the state level) will help the estimated 25 percent of Americans on insulin who have been forced to ration the drug because of cost, and will prevent some of the 600 annual American deaths from diabetic ketoacidosis, the fate from which I’m trying to save my patient.

    Indeed, laws capping co-payments for insulin are welcome news both financially and medically to patients who depend on the drug for survival. However, in their current version, such laws might backfire, leading to even more diabetes-related deaths overall.

    How could that be true? Thanks to the development of new drugs, insulin’s role in diabetes treatment has been declining over the past decade. It remains essential to the small percent of patients with type 1 diabetes, including my patient. But for the 90 percent of Americans with diabetes who have type 2, it should not routinely be the first-, second-, or even third-line treatment. The reasons for this are many: Of all diabetes medications, insulin carries the highest risk of causing dangerously low blood sugar. The medication most commonly comes in injectable form, so administering it usually means painful needle jabs. All of this effort is rewarded with (usually unwanted) weight gain. Foremost and finally, although insulin is excellent at tamping down high blood sugar—the hallmark of diabetes and the driver of some of its complications—it is not as impressive as other medications at mitigating the most deadly and debilitating consequences of the disease: heart attacks, kidney disease, and heart failure.

    Large clinical trials have shown that two newer classes of diabetes medicines, SGLT2 inhibitors and GLP-1 receptor agonists, outperform alternatives (including insulin) in reducing the risk of these disabling or deadly outcomes. Giving patients these drugs instead of older options over a period of three years prevents, on average, one death for about every 100 treated. And SGLT2 inhibitors and GLP-1 receptor agonists pose less risk of causing dangerously low blood sugar, generally do not require frequent injections, and help patients lose weight. Based on these data, the American Diabetes Association now recommends SGLT2 inhibitors and GLP-1 receptor agonists be used before insulin for most patients with type 2 diabetes.

    When a young person dies from diabetic ketoacidosis because they rationed insulin, the culprit is clear. But when a patient with diabetes dies of a heart attack, the absence of an SGLT2 inhibitor or GLP-1 receptor agonist doesn’t get blamed, because other explanations abound: their uncontrolled blood pressure, the cholesterol medication they didn’t take, the cigarettes they continued to smoke, bad genes, bad luck. But every year, more than 1,000 times more Americans die of heart disease than DKA, and of those 700,000 deaths, a good chunk are diabetes-related. (The exact number remains murky.) Diabetes is a major reason that more than half a million Americans depend on dialysis to manage their end-stage kidney disease, and that about 6 million live with congestive heart failure. The data are clear—SGLT2 inhibitors and GLP-1 receptor agonists could help reduce these numbers.

    Still, uptake of these lifesaving drugs is sluggish. Only about one in 10 people with type 2 diabetes is taking them (fewer still among patients who are not wealthy or white). The main cause is simple and stupid: American laws prioritize profits and patents over patients. Because SGLT2 inhibitors and GLP-1 receptor agonists remain under patent protections, drug companies can charge exorbitant rates for them: hundreds if not thousands of dollars a month, sometimes even more than insulin. Doctors spend hours completing arduous paperwork in the hopes of persuading insurers to help our patients, but we’re frequently denied anyway. And even when we do succeed, many patients are left with painful co-payments and deductibles. The most maddening part is that despite their substantial up-front expense, these medications are quite cost-effective in the long run because they prevent pricey complications down the road.

    This is where addressing the cost of insulin—and only insulin—becomes problematic. Doctors are forced daily to decide between the best medication for our patients and the medication that our patients can afford. Katie Shaw, a primary-care physician with a bustling practice at Johns Hopkins, where I’m a senior resident, told me that plenty of her patients can’t afford SGLT2 inhibitors and GLP-1 receptor agonists. In such instances, Shaw is forced to use older oral alternatives and occasionally insulin. “They’re better than nothing at all,” she said.

    If the cost of insulin is capped on its own, insulin will be more likely to jump in front of SGLT2 inhibitors and GLP-1 receptor agonists in treatment plans. That will mean more disease, more disability, and more death from diabetes.

    Medicare patients might avoid some of these effects thanks to provisions in the IRA allowing Medicare to negotiate drug prices and capping out-of-pocket spending on prescriptions at $2,000 a year. The law also guarantees price negotiations for a handful of medications, but SGLT2 inhibitors and GLP-1 receptor agonists won’t necessarily be on the list. And most Americans are not on Medicare. Already, Shaw said, the patients in her practice who tend to be least able to afford SGLT2 inhibitors and GLP-1 receptor agonists are working-class people with private insurance. Some health centers, including the one Shaw and I work at, enjoy access to a federal drug-discount program that can make patent-protected medications, including SGLT2 inhibitors and GLP-1 receptor agonists, more affordable for the uninsured. But most Americans without insurance aren’t so lucky.

    It would be cruel to choose between a world in which more people with type 2 diabetes are nudged toward a drug that won’t stave off the most dangerous complications, and one in which those with type 1 diabetes are priced out of life. In place of capping the out-of-pocket cost of just insulin, lawmakers should cap the out-of-pocket cost of all diabetes medications. This will both protect Americans dependent on insulin and smooth SGLT2 inhibitors’ and GLP-1 receptor agonists’ path to their revolutionary public-health potential.

    The argument for lowering the cost of these drugs for patients is the same as the argument for insulin affordability: that it is both foolish and inhumane to make lifesaving diabetes medications unaffordable when their use prevents costly and deadly downstream complications.

    Patients like mine need affordable access to insulin. But even more need access to SGLT2 inhibitors and GLP-1 receptor agonists. If the laws stop at insulin, many Americans could die unnecessarily—not from inadequate access to insulin, but from preferential access to it.

    Michael Rose

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