The long history of underground drug use abounds with secret societies—colorful cliques of like-minded individuals surreptitiously experimenting with newfangled compounds in an effort to understand their mysteries. Participants from the Phase 2a study are now continuing in a 26-week extension trial, with results expected in early 2026. In my view, a next study with higher nimacimab dosing is the logical step to fully define its role in clinical practice.” No neuropsychiatric side effects – such as anxiety, depression, or insomnia – were observed with nimacimab, either alone or in combination. “The 200 mg monotherapy arm provided important pharmacokinetic insight, showing that lower-than-expected drug exposure may have limited the observed effect and informing the dose-ranging strategy we are developing,” said Puneet Arora, MD, Skye’s Chief Medical Office. The 2019 Health Survey for England estimated that over 12 million adults were living with obesity – 28 per cent of the population in England – while a further 16 million (36 per cent) were overweight. It is offering incentives such as vouchers for shops, gym discounts and cinema tickets for people who eat healthily and exercise more. Losing weight can help to reduce the risk of obesity-related illness which in turn can reduce pressure on the NHS, cut waiting times, and realise wider economic benefits. Tackling obesity is a key part of the NHS Long Term Plan – it can have devastating consequences for the nation’s health, leading to serious health conditions and some common cancers as well as resulting in significant pressure on NHS services. These pilots build on our ongoing work to tackle obesity – including introducing calorie labelling on menus to empower people to make informed decisions and investing in school sport to give children an active start in life. What obesity drugmakers see next in the market: More pills, easier access and drug combinations Year after year, Mary Bucklew strategized with a nurse practitioner about losing weight.Obesity is most often measured by body mass index (BMI), a calculation of body weight compared with height.Visit the Yale Obesity Research Center (Y-Weight) to learn more about Yale School of Medicine’s ongoing research on anti-obesity drugs and how they can help people with obesity.In a small early trial of amycretin with just 125 participants, people lost 24 per cent of their weight, on average, after 36 weeks.Novo Nordisk's oral version of its obesity injection Wegovy could enter the market by year-end, while Eli Lilly's pill orforglipron could launch next year.It’s a milestone for the industry, which has struggled to make effective pill versions of the weight-loss injections for years. In a recent randomized and controlled phase 3 clinical trial study published in the New England Journal of Medicine, researchers at Chicago's Northwestern University studied the drug's impact on weight loss for nearly 2,000 individuals in 16 countries. Further studies in primates with type 2 diabetes and obesity showed that activating the receptor lowered body weight and reversed their diabetes by increasing insulin sensitivity and lowering blood sugar, triglycerides, and cholesterol. Here's how much weight loss drugs could cost for patients under the new agreements, based on the details shared so far. Subscribe to the Policy Currents Newsletter One way that Indian and Chinese pharmaceutical companies plan to slash that price is by developing biosimilars, cheaper versions of expensive brand-name drugs. Semaglutide and tirzepatide are weekly injections that can induce an average body-weight reduction of between 12% and 18%. A long queue of companies is developing copies of the complex biological drugs, and some are racing to create modified or improved versions to compete in the global market. She has seen no weight loss after three months. Nearly all GLP-1 agonists approved in the US for diabetes also induce some weight loss. Losses were modest—around 5–10%—and people typically regained weight as soon as they stopped taking the drugs. Rimonabant, the first blocker of cannabinoid receptor 1 for weight loss, was approved in Europe in 2006 but pulled 2 years later after the drug was linked to thoughts of suicide. Medicare, which primarily provides health care for people aged 65 and older, was specifically prohibited by law in 2003 from covering weight-loss treatments. As Scientific American reported in October, most private insurance companies and federal health programs do not cover weight-loss drugs. Those who took semaglutide lost weight, but weight loss alone didn’t seem to explain improvements in the participants’ heart health; some experts think other, still-unknown mechanisms of the GLP-1 agonist may be involved. Indeed, Dresser says producers of such chemicals can glean the drug’s molecular structure by referring to patent literature submitted by pharmaceutical sponsors to regulatory agencies like the FDA. Despite his commitment to diet and exercise, he had found himself unable to drop weight. However, he eventually stopped taking retatrutide after a negative experience that he attributes to the drug’s interaction with a proton pump inhibitor he was taking to manage acid reflux—itself the result of some anabolic steroids he had taken a year earlier. “The pitch for reta is it just puts that stuff on autopilot … it makes your cutting, your weight-maintenance effortless. “I have an unhealthy obsession with pharmaceutical interventions.” Expanding how to access these innovative new drugs will ensure as many eligible patients as possible have the opportunity to try these treatments if they are right for them to help achieve a healthier weight.Still, pharmaceutical companies are racing to investigate new, improved relatives of semaglutide.There are also concerns about supply issues, given the shortages seen with GLP-1 drugs, Wegovy and Ozempic.Saxenda, which is taken daily and typically offers more modest weight loss, brought in more than $900 million in sales in 2020.Researchers say the combination has the potential to reshape the future of obesity treatment.Such vendors—sometimes called “grey market pharmacies”—typically trade in alternative forms of commonly used psychoactive drugs, as well human-growth hormone, anabolic steroids, and other “gear” prized among the power-lifting and body-hacking sets.KFF polling found about half of adults in the U.S. would be interested in taking prescription weight-loss drugs, though interest drops if the drug is not covered by insurance or after hearing patients might gain weight back after stopping use. What's more, Medicare is negotiating the price of Novo Nordisk's semaglutide – the active ingredient in Ozempic, Wegovy and the company's diabetes pill Rybelsus – effective in 2027, which could further cut into revenue. Novo Nordisk cut its profit and sales forecast in July, saying compounded drugs had cut into Wegovy's market. TD Cowen analyst Michael Nedelcovych said that's largely because Eli Lilly's injections are superior to Novo Nordisk's drugs in terms of safety and efficacy. Adults with migraines and obesity are good candidates for this weight-loss medication. It was originally used as a short-term medication to jump-start weight loss, but now newer medical guidelines have added it to long-term therapy. Phentermine is the oldest and most widely used weight loss medication. GLP-1 pills for obesity are closer than ever.High rates of obesity and potential market demand for the weight-loss drugs could result in a significantly higher impact on total health spending in the U.S. than in peer nations.The daily pill appears to be slightly more effective than a competing oral GLP-1 from Eli Lilly called orforglipron, based on data from separate phase three trials.Unlike the semaglutide-cagrilintide combo, amycretin is a single-molecule drug that activates both the amylin and GLP-1 receptors."One tool does not work for each person, and one tool often is not enough over the lifetime of a person to control or to mitigate the health impact of that condition," she says.It's important that people continue to make lifestyle changes to help their weight loss, such as eating right and exercising.Behind them is a slate of drugmakers – from biotech upstarts to pharma giants – racing to win a slice of what some analysts expect could be a roughly $100 billion market by the end of the decade.He points to the importance of both clinical trials, and the significance of surpassing the 20% loss in body weight.However, despite coming in tablet form, oral semaglutide – sold under the brand name Rybelsus for type 2 diabetes – can still be complicated to take, doctors say.GLP-1 drugs mimic a hormone the body produces after eating, which can decrease appetite. It’s based on the amount and size of fat cells in your body. For best results, providers recommend you use the medication alongside a reduced-calorie diet and a regular exercise routine. Be prepared to give yourself once-weekly injections of the medication at home. If you have Type 2 diabetes, there’s also the risk of your blood sugar levels going too low. Currently available long-term anti-obesity medications for adults include orlistat, naltrexone/bupropion (NAL/BUP) extended release (ER), liraglutide, phentermine/topiramate ER, semaglutide, and tirzepatide (Table 1).“Just like diabetes, just like hypertension, obesity management requires close follow-up.However, Wegovy contains higher doses of it and is designed for weight loss.If all goes according to plan, FDA approval should follow, and marketability by late 2026 or early 2027 could be possible, based on the timelines of other drugs in the category.In theory, the GLP-1 drugs could potentially affect your kidneys, thyroid and pancreas.Although the long-term implications of taking the higher dose of the drug are still unknown, there have been relatively few side effects of the lower-dose version of semaglutide treating diabetes.The once-monthly injection entered Phase 3 clinical trials in March 2025.Several trials have reported that 35% to 45% of GLP-1 weight loss is not fat, but “lean mass” including muscle and bone. The Danish drugmaker reported last year that a late-stage study in people who don’t have diabetes showed that the daily pill led to an average weight loss of 15% over 68 weeks, a similar result as seen in trials of Wegovy. It is expected to outpace Novo Nordisk’s Ozempic — a diabetes drug used so commonly to shed pounds that comedian Jimmy Kimmel joked about it at the Oscars — and Wegovy, a version of the drug also known as semaglutide approved for weight loss in 2021. In June, Zealand released positive data from an early trial showing that a high dose of the drug helped people lose nearly 9 percent of their body weight on average at 16 weeks. This new drug, semaglutide, was first approved for diabetes in 2017 under the brand name Ozempic and then in 2021 for weight loss as Wegovy. At the end of the study, nearly 35% of the 1,059 people who completed the trial lost at least 20% of their body weight—a level no other weight-loss drug has achieved. What's the difference between Ozempic and Wegovy? For instance, brown adipose tissue can break down glucose and fat molecules to create heat and maintain body temperature. One promising avenue might be developing medication that stimulates natural fat-burning pathways, perhaps manipulating certain types of fat. More innovative weight-loss pills may just be around the corner. It wouldn’t just affect numbers on weighing scales but would improve patients’ quality of life, too. He promotes wellness through lifestyle changes, emphasizing exercise, healthy eating, and supportive relationships in addition to traditional metric goals. ABOM, is a board-certified family medicine and obesity medicine physician currently at Norman Regionals Primary Care South OKC clinic. For about two years, compounded versions of semaglutide and tirzepatide were permitted in the U.S. due to shortages. In April 2025, they banned the sale of “counterfeit” semaglutide and tirzepatide. The researchers also considered the impact of socioeconomic factors on the effectiveness of expanded drug access. It exacerbates conditions such as type 2 diabetes, cardiovascular disease, and certain cancers. Centers for Disease Control and Prevention, about 74% of Americans are considered overweight, with about 43% of those individuals considered obese. The previous cash price for Wegovy matched that of a full dose of Zepbound, a competing drug from competitor Eli Lilly. This is the first article in a series about new obesity drugs that are transforming patients’ lives, dividing medical experts, and spurring one of the biggest business battles in years. The researchers noted that participants on the higher ecnoglutide doses continued to lose weight through to week 48, so the drug may benefit people who haven't gotten the results they wanted on other GLP-1 treatments. Those taking ecnoglutide lost, on average, 9-13% of their body weight after 40 weeks, while people who received the placebo experienced little to no weight change. The weight loss treatment market is currently dominated by two drugmakers, but as more pharmaceutical companies enter the field, increased competition could lead to lower costs for consumers. Users are advised to follow a healthful, reduced-calorie diet and to exercise regularly while using the drugs. “Our priority is protecting public health by ensuring all active ingredients used in GLP-1 drugs are obtained from compliant manufacturers,” he said. The human brain seems to have a ‘set point’ for how much fat the body stores, and drugs simply mask that set point rather than changing it. In obese mice, retatrutide results in greater body weight loss and energy expenditure than tirzepatide through glucagon receptor activation. A phase 2 trial demonstrated body weight changes from baseline to week 24 of −6.7% with mazdutide 3 mg, −10.4% with mazdutide 4.5 mg, −11.3% with mazdutide 6 mg, and 1.0% with placebo. At week 12, participants receiving mazdutide at 6 and 9 mg had body weight losses of 6.1% and 11.7%, respectively (Ji et al., 2021, 2022). In a phase 1b clinical trial in Chinese adults with overweight or obesity, mazdutide up to a dose of 10 mg was well tolerated and had an overall safety profile similar to those of other GLP-1-based therapies. Currently, CagriSema is undergoing phase 3 trials in people with overweight or obesity and various related conditions (Table 4). It’s probably no coincidence that government statistics show that more than 30% of Americans are overweight and more than 42% have obesity. Ozempic and Mounjaro are for people with type 2 diabetes These new drugs often quiet the 'food noise,' or brain chatter about food Medical Expert Insights Don't expect costs to go down anytime soon, though, even as other new drugs are poised to hit the market. "It's a great drug, but it's about twice as expensive as it should be" when its health benefits are weighed against its cost and potential to drive up overall medical spending and health premiums, said Rind. But Qsymia also helped patients lose a substantial amount of weight, Rind said. Related article Novo Nordisk to increase supply of weight-loss drug Wegovy But anyone who has ever dieted can tell you that losing weight is hard and that long-term weight loss requires sustained effort, which can sometimes feel Herculean, even impossible. People want to lose weight to look a certain way “now,” and they also want to live longer and healthier lives, with a lower risk of developing serious health conditions in the future. Increased off-label use of these drugs is contributing to supply shortages for people who use these drugs for diabetes and employer health plans and insurers are scrutinizing the prescribing of the drugs. The weight-loss benefits of these drugs have led to their prescribed use for obesity or overweight treatment. As a result, Medicaid coverage of GLP-1 drugs for obesity treatment is optional for states, while coverage for other indications (diabetes, cardiovascular disease, and sleep apnea) is required. Table 2. Percentage of U.S. Adults Reporting GLP-1 Agonist Use, by Age and Sex At least five tirzepatide-like therapies are progressing through clinical trials, with the first expected to hit the market by 2028. Inspired by tirzepatide’s success, many companies are advancing other drugs that engage GLP-1 and GIP receptors. But, he says, drugs such as tirzepatide can override this natural mechanism. That’s a problem as many private health insurance plans still do not cover obesity medications. With more than four in 10 Americans—and nearly 2 billion people worldwide—affected by obesity, the promise of these new drugs to treat the world’s fastest growing chronic disease has been clashing with the reality of their cost and access problems. A steady stream of weight loss drugs, which mimic naturally occurring hormones, are in the pipeline. One in four people taking pemvidutide, for example, dropped out because these side effects were too intense. The other GLP-1 and glucagon combo drug is pemvidutide, being tested for both obesity and fatty liver disease. Two other drugs, from other pharmaceutical companies, mimic GLP-1 and glucagon, a hormone with receptors in the liver. Novo Nordisk, the company that makes Ozempic/Wegovy, is working on a drug combination of semaglutide and cagrilintide, which mimics amylin. The main gut hormones being mimicked and combined in different medications are GLP-1, GIP, glucagon, and amylin—another hormone released by the pancreas which regulates blood glucose levels, slows down digestion, and reduces food consumption. "These drugs have the potential to bring about substantial weight loss, particularly in the first year," says Juan Franco, co-lead researcher from Heinrich Heine University Düsseldorf, Germany. Across the reviewed studies, tirzepatide, semaglutide, and liraglutide consistently led to significant weight loss over one to two years compared with placebo, and the benefits appeared to continue during ongoing treatment. The World Health Organization (WHO) requested these reviews to help shape upcoming recommendations on using these medications for obesity treatment. Three new Cochrane reviews report that GLP-1 drugs can lead to meaningful weight loss, although the strong involvement of pharmaceutical companies in many studies raises concerns. He says a small number of patients can't tolerate the side effects, but it seems that many people are interested in trying the drug. Aronne has been studying weight loss drugs for many years and is a consultant for Eli Lilly. In the tirzepatide study, 36% of people taking the highest dose lost 25% or more of their body weight. Now, the company is seeking approval from the Food and Drug Administration for tirzepatide for chronic weight management in people who have obesity or are overweight with weight-related conditions, but don't have diabetes. The drug is already approved as an injectable prescription medicine for people with Type 2 diabetes. An earlier version of this story misspelled the name of the medication Mounjaro. Some people experience nausea, diarrhea, constipation, and vomiting. Given what's happened with the spotty insurance coverage of Wegovy, clinicians who treat obesity anticipate similar challenges. "These medicines are the opening to a whole new era of treating metabolic disease," says Dr. Louis Aronne, an obesity specialist at Weill Cornell Medicine, one of the co-authors of the SURMOUNT-1 study. Eli Lilly is seeking FDA approval for tirzepatide for chronic weight management. In studies of Zepbound, patients taking the highest dose lost around 21 percent of their body weight. Hot on the heels of semaglutide is Eli Lilly’s tirzepatide, approved as Mounjaro in 2022 for diabetes and as Zepbound in 2023 for weight management. Called liraglutide and sold under the brand name Saxenda, the weekly injectable led to a nearly 3 percent reduction in body weight on average in trial participants who took it. The discovery would eventually launch a new class of diabetes drugs known as GLP-1 receptor agonists, the first of which was approved in 2005. The agreements will cut the prices the government pays for the drugs, introduce Medicare coverage of obesity drugs for the first time for certain patients and offer discounted medicines on the government's new direct-to-consumer website launching in January, TrumpRx. Patients inject the drugs once a week at home and can lose about 12% to 15% of their body weight (though many hit a plateau after that). However, it appears that if people taking the drugs stop, they regain the weight they lost — and the health problems that came with it. An earlier trial of tirzepatide showed weight loss of between about 15% and about 22% of body weight, or about 35 pounds to about 52 pounds, depending on the dose. It builds on the 15% weight loss seen for Wegovy by adding a target in addition to GLP-1, called GIP. The company published data in the journal JAMA Network Open this week on use of a twice-daily pill called danuglipron in people with type 2 diabetes. Other oral GLP-1 drugs are in development that can be taken with food, including two from Pfizer. They can’t eat, drink anything other than 4 ounces of water or take other medicines within 30 minutes of taking the drug, or its effects could be diminished, she said. Do you need a prescription for Wegovy? What seems to be happening is that semaglutide revs up the cells’ natural antioxidant defenses. In other words, the drug helped the cells fight back, recover and even store energy for the challenges ahead. They exposed human retinal cells to high sugar and oxidative stress, then treated some with semaglutide. With prevalence projected to rise sharply over the coming decade, researchers are under pressure to find interventions that protect retinal tissue earlier, before damage becomes clinically obvious and functionally irreversible. Diabetic retinopathy remains one of the most common and consequential complications of diabetes, not because it is dramatic in onset but because it is quietly cumulative – retinal microvasculature does not fail overnight, it frays. When it comes to deciding whether one of these new weight loss drugs is right for you, the guidance of a healthcare provider is essential. One of the biggest challenges for patients interested in these weight loss medications is the cost. For Mounjaro, weight loss results were even more remarkable, with some participants losing up to 20% of their body weight during trials. In clinical trials, participants taking Wegovy lost an average of 15% of their body weight over a year. GLP-1 Drugs Affect Your Gut and Brain The Trump administration’s November announcement would expand Medicare eligibility for GLP-1s and related medications to include obesity, perhaps as early as spring. “For people on these medications, the process is much more accelerated.” Several trials have reported that 35% to 45% of GLP-1 weight loss is not fat, but “lean mass” including muscle and bone. “We have not seen this degree of weight reduction,” she said.Some analysts argue that their experimental drugs, most of which are still in mid-stage development, have not differentiated themselves enough from existing treatments.In phase II testing, Eli Lilly’s retatrutide — dubbed ‘triple G’ for its ability to target GLP-1, GIP and glucagon receptors — delivered an average weight reduction of 24% after 48 weeks, setting a new benchmark for obesity treatments1 (see ‘Shedding weight’).Health care professionals use the Body Mass Index (BMI), a measure of your weight in relation to your height, to define overweight and obesity.A pill version of semaglutide approved for diabetes, called Rybelsus, hasn’t been used as widely as Ozempic in part for that reason, doctors say.That could look like combining a GLP-1 with one of the existing treatments for fatty liver disease. The drugs, called GLP-1 receptor agonists, were developed to treat Type 2 diabetes, the prevalence of which has skyrocketed in recent decades along with rates of obesity in America. Ozempic, one of the drugs developed for Type 2 diabetes, caught the attention of the public and drug makers after it proved to help patients shed pounds. Producing pills is generally cheaper than making drugs delivered via injections, so the cost for the new oral medications could be lower. Food and Drug Administration on Monday gave the green light to a pill version of the blockbuster weight-loss drug Wegovy, the first daily oral medication to treat obesity. While no specific vitamin or supplement is considered a “treatment” for obesity or overweight, certain ones help support metabolic health. The GLP-1 medicines are already used to treat diabetes, and they generate $23 billion in annual sales. For drugmakers, this represents one of the biggest financial opportunities ever. A few months ago, Wegovy was approved for use by adolescents, too. In the U.S., 42% of adults and 20% of children are estimated to have obesity. Medicare plans are prohibited by law from covering prescription medications taken solely for weight loss. Coverage for obesity care and weight-loss medications varies widely among insurance plans. People with large employer coverage pay an average of nearly $70 per month in out-of-pocket costs for semaglutide when these drugs are covered by their health plan, though this is a small share of the total cost of the drug. Medicare prohibits coverage of drugs used only for weight loss (though Part D plans are allowed to cover Wegovy when used to reduce the risk of heart attack and stroke for certain beneficiaries) and Medicaid coverage of weight loss drugs varies by state. What's better for weight loss, Mounjaro or Ozempic? New study provides answer In other words, the drug helped the cells fight back, recover and even store energy for the challenges ahead.As soon as the public-private partnership TrumpRx launches, patients using the service will pay roughly $350 for a month's supply of the injectable drugs, according to senior administration officials.However, many people stop taking the drugs due to common side effects, including nausea and vomiting.And until we are able to have messy conversations about this, do a better job of bringing in multiple perspectives and multiple truths into the conversation, people are going to be left out.”This drug's timeline has been rocky for Novo Nordisk; early trial data published in February resulted in a $125 billion dip in share value and the eventual ousting of its CEO.The average age of the participants was 57, and the average weight was 101 kilograms (223 pounds).Phentermine is the oldest and most widely used weight loss medication.These medications have side effects, some of which could be severe. Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. It is not known if Wegovy® tablets are safe and effective for use in people under 18 years of age. Wegovy® contains semaglutide and should not be used with other semaglutide-containing products or other GLP-1 receptor agonist medicines. Wegovy® pill is only approved in the US and will be available in 1.5 mg (starter dose), 4 mg, 9 mg, and 25 mg.3 For updates and information about the Wegovy® pill, please visit Mounjaro and Zepbound mimic the effects of GLP-1 as well as GIP, a type of hormone that helps regulate blood sugar by stimulating insulin. The people who took retatrutide also reported a 76% reduction in knee pain after the 16 months, according to the data. And, perhaps in an effort to curb the prevalence of compounded semaglutide in the US, Novo Nordisk has also launched the online pharmacy NovoCare, which allows Stateside residents without insurance to buy Wegovy for $499 a month and have it shipped to their home. UBT251 is a triple agonist – known colloquially as a "triple-G" medication – which targets glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptors. The only over-the-counter medicine for weight loss currently approved by the FDA is Alli (orlistat). Some weight management medications are designed for short-term use and others for long-term use. The following medications can potentially cause variable weight gain in some individuals. Last year, phase II trial results indicated that monlunabant can still cause anxiety, irritability and sleep disturbances. The drug, known as rimonabant, was withdrawn from the market after less than three years, and rival companies abandoned similar candidates. Once-monthly injectables are in the works, but GLP-1 pills — led by a drug called orforglipron produced by Eli Lilly — could arrive first, hitting the market as soon as next year. Companies are also exploring alternatives to once-a-week injections, which can be difficult to incorporate into people’s routines and come with manufacturing challenges. Carel le Roux, a metabolic medicine specialist at University College Dublin who consults for several drug makers, says the findings suggest that “the more mechanisms we add, the more benefit we get”. A 2016 study from the University of California, Los Angeles, suggests that 29% of people who are medically defined as obese are otherwise metabolically healthy. Saxenda, which is taken daily and typically offers more modest weight loss, brought in more than $900 million in sales in 2020. Chronic weight management means years, if not decades, of treatment. About 42% of people in the US meet the CDC’s definition of obesity. Is retatrutide more effective than GLP-1 drugs? Here & Now’s Peter O’Dowd spoke with Zhang about her experience acquiring the drug, and what’s motivating people to seek out these underground markets. Her reporting revealed people searching the web and using the app Telegram to buy products, likely from China, that purport to be the same drug. In a clinical trial, retatrutide showed promising results. It is intended to be used indefinitely, in combination with a healthy diet and exercise. This progression can help to alleviate side effects, which include gastrointestinal symptoms, headache, dizziness, and fatigue. Wegovy is a brand name for semaglutide, a GLP-1 receptor agonist. KFF is an endowed nonprofit organization providing information on health issues to the nation. KHN (Kaiser Health News) is a national newsroom that produces in-depth journalism about health issues. "It's become more and more obvious over the years that obesity is a medical issue, not a lifestyle choice," Rind said. Rind sees the new, more effective therapies as another way to help dispel the notion that patients "aren't trying hard enough." Safety also became more critical as the field shifted from acute to chronic use, a transition that began in 1999 with a new drug called Xenical (orlistat).Obesity drug coverage in Medicaid remains limited, with 13 state Medicaid programs covering GLP-1s for obesity treatment under FFS as of January 2026 (Figure 1).That price point, and spotty insurance coverage for weight loss drugs in the U.S., have been significant barriers to access for some patients.A related government survey found that almost half of US adults said they have tried to lose weight in the last 12-month period.It was approved in 1959 for short-term obesity treatment at a dose of 15.0 to 37.5 mg/day (Gadde et al., 2011).Naltrexone (NAL) is an opioid receptor antagonist approved as a treatment for opioid dependency and alcohol dependence. “We’ve taken those normal signaling molecules in your body and we’ve turned them into medicines,” Skovronsky said. Dr. Dan Skovronsky, Eli Lilly’s chief scientific and medical officer, told NBC News that retatrutide is attempting to harness the body’s own mechanisms that metabolize food and tell the body when to stop eating. She was not involved with the trial, although she has previously served on an advisory board for Ozempic and Wegovy-maker Novo Nordisk. Early evidence suggests that when people stop taking the medications, they gain the weight back. Research has shown that with diet and exercise alone, about a third of people will lose 5% or more of their body weight, said Dr. Louis Aronne, director of the Comprehensive Weight Control Center at Weill Cornell Medicine. Rather than relying solely on diet, exercise and willpower to reduce weight, tirzepatide and other new drugs target the digestive and chemical pathways that underlie obesity, suppressing appetite and blunting cravings for food. “The potential indications for myostatin drug discovery are going to explode in the coming years.” This effort has its origin over two decades ago with studies that Lee did showing that knocking out myostatin not only increased muscle growth but also reduced body fat. Based on the results of these trials, one of these companies, Scholar Rock, is now seeking FDA approval for their myostatin inhibitor, which is based on a fundamental mechanism discovered by Lee by which myostatin is regulated. This story has been corrected to show the length of time study participants lost weight before plateauing was 14 months, not 16 months, and the last name of the Houston physician to Sadhu, not Sudhu. She’s considering going back on Wegovy after it’s approved. Food and Drug Administration included both Ozempic and Wegovy on its drug shortages list. Food and Drug Administration's drug shortages list in 2023. But given that more than two-thirds of the US adult population is now overweight or obese, Americans are clearly not meeting these guidelines. Being active also reduces the risks of developing conditions like heart disease, type 2 diabetes, and some cancers. Among ACA Marketplace plans with these drugs on formulary, prior authorization is required by most plans. Drugs solely approved to treat obesity have minimal to no coverage on most ACA Marketplace formularies. The ACA Marketplaces represent a small share of people with private health insurance, as most people with private coverage have plans sponsored by their employers. So, the broader question is whether it is both clinically and economically better to aggressively treat certain high-risk obese patients sooner, or risk downstream cost and clinical complexity later. Like drugs for other health conditions, Ozempic and Wegovy are intended to be chronic medications -- ones that only work while you're taking them. The results from the early stages of trials suggest people are losing up to almost a third of their body weight, but Dr Helen says that itself comes with risk. Although not all experts went as far as to characterize the new treatment as "game changing," many agreed that semaglutide could lead to the advent of a new generation of drugs, which could change the way obesity is treated. Current anti-obesity drugs on the market result in a weight loss of about 6% to 12%, according to Kushner. On average, over half of those who received the drug itself lost nearly 15% of their body weight, and over a third achieved a weight loss of at least 20% of their weight. To be sure, these are not direct comparisons because the drugs were not compared in a head-to-head clinical trial. Novo Nordisk’s semaglutide was found to reduce body weight, on average, by around 15%, or about 34 pounds, after 68 weeks. She’s gained back about 15 pounds in the nine months since she completed the trial, but said she still thinks the weight loss is sustainable with healthy lifestyle choices. After 24 weeks, patients taking the highest dose — 12 milligrams — lost, on average, 17.5% of their body weight, the equivalent of, on average, 41 pounds, according to the company. It's difficult to directly compare the results of separate clinical trials on the two drugs to compare their efficacy. There are also no FDA-approved drug products containing berberine, the agency adds. But the patches don’t contain actual GLP-1 medications — “they have herbs and other random things depending on the patch,” Jay says. GLP-1 drugs are available only with a prescription and cost hundreds of dollars a month, while anyone can buy the patches and they may cost less than $1 per unit. The scientists are hoping not only for greater weight loss effectiveness but also for a better chance of a person keeping the weight off. And join us next week on the Chasing Life podcast when we explore the business side of these medications. This is the time to start changing some eating patterns that will be beneficial for weight loss. “Just like diabetes, just like hypertension, obesity management requires close follow-up. All the new weight loss drugs mimic the action of a naturally occurring substance called glucagon-like peptide 1 (GLP-1). What long term effects, if any, will they have on patients who will need to take them for the rest of their lives to maintain their weight loss? Tufts Now recently spoke to several faculty experts to gain insights into these drugs’ future potential for solving the epidemic chronic diseases of overweight and obesity. But while Novo Nordisk's pill is a peptide medication, orforglipron is a small-molecule drug. Both drugs work by mimicking the GLP-1 gut hormone to suppress appetite and regulate blood sugar. Some experts and analysts believe they could fundamentally shift the market, helping more patients access treatment and alleviating the supply shortfalls of existing injections. Novo Nordisk is also testing semaglutide in Alzheimer's, with initial late-stage trial results expected this year. Crable added that new direct-to-consumer programs from Eli Lilly and Novo Nordisk — which let patients pay cash for treatments at less than half their monthly list price — may also discourage employer coverage. While many are GLP-1 based, others target different biological pathways, some of which might offer similar weight loss with a lower incidence of gastrointestinal side effects like nausea. Beyond GLP-1s, the weight loss drug pipeline is bursting with over 170 candidates from 82 manufacturers. For example, in cases such as MASH, GLP-1 therapies may represent a lower-cost treatment option compared to other approved drug therapies. This is because the population affected by the new indications overlaps almost completely with the population that already qualifies for treatment under the weight loss indication. Nadia Ahmad, the medical director for Eli Lilly and Company’s obesity product development, says this long string of safety issues and product failures is why the field has been considered such a gamble for pharma companies.Ask your health care professional about lifestyle treatment programs for weight management that will work for you.The future of the industry will likely also include drugs that can achieve even greater weight loss than the current treatments on the market.Some patients find that medication-induced weight loss lessens rather than improves fitness, because another side effect is muscle loss.But because of cost, for example, negative side effects, or supply shortages, many people are having to transition off of them — while trying not to regain the weight.The American Academy of Pediatrics’ guidelines call obesity and overweight “one of the most common pediatric chronic diseases in the U.S.,” affecting some 14.4 million children and adolescents.Semaglutide mimics a gut hormone, GLP-1, that’s secreted after people eat. In an August note, Goldman Sachs analysts forecast daily oral pills will capture 24% share — or around $22 billion — of the 2030 global weight loss drug market, which they expect to be worth $95 billion. "You're paying for the GLP-1 drug with the hope that obesity or these other conditions will improve, so that health-care costs for these individual employees will get better as you move forward," Stich said. Stitch said employers also have questions about how oral obesity drugs, which could be available as soon as 2025, could affect demand and costs. Stanford, who is on the executive committee of the AAP’s section of obesity, said that the new guidelines are the first in 16 years and shift away from a prior approach that counseled “watchful waiting” while lifestyle and diet-related changes were tried. Similarly, they say pediatricians should offer adolescents age 13 and older with severe obesity an evaluation for metabolic and bariatric surgery. “Even today, healthcare costs are displacing the true determinants of health, which are education, a safe environment, physical infrastructure to work, play, walk, bike, all of that. But the currently approved drugs, synthetic versions of these hormones, are large molecules that are expensive and time-consuming to manufacture, which has meant high prices for consumers and growing drug shortages. The drugs in this class are agonists, or mimics, of natural gut hormones that affect the body’s metabolism and hunger signals in the brain. Patients taken off the drug gained back more than half their weight loss. Those taking the combination were significantly more likely to hit major weight-loss milestones, such as losing percent of their body weight. Obviously, feeling better and being healthier is a wonderful thing, but it’s very difficult when people treat you like a different person,” she says. “I’ve said time and time again, one of the main motivators for me wanting to lose weight is that people treat you differently. Cliett says that since she’s gained weight, she’s felt people are less kind to her than they used to be. (That start-up was later acquired by Eli Lilly, which has yet to release results from the now-completed 500-person trial that Cook joined.) In 2021, Aditum helped to launch a company focused on repositioning bimagrumab as a weight-loss solution. The drug was “very potent and actually quite safe”, says Mark Fishman, Novartis’s former president of biomedical research. Novartis, a pharmaceutical company in Basel, Switzerland, discontinued the drug’s development in 2017. Among those who completed the full treatment, the average weight loss increased to 22.7 percent. Patients who received CagriSema lost an average of 20.4 percent of their body weight. This will explore innovative ways to best utilise promising medicines and digital technologies to help NHS patients achieve a healthy weight. This doesn’t happen to everyone, and there isn’t enough research yet to determine which individuals may be most at risk for losing muscle when they take weight loss medications, says Jay. By the end of the study, people taking the lowest dose of eloralintide lost 9.5 percent of their body weight on average, or about 23 lb. In a mid-stage clinical trial, researchers randomly assigned 263 adults with obesity but not diabetes to receive weekly shots of eloralintide or a placebo for 48 weeks. “Given the high rates of obesity and diabetes, additional treatment options are very welcome,” says Marilyn Tan, MD, a clinical professor of endocrinology at the Stanford University School of Medicine and the chief of the endocrine clinic at Stanford Health Care in California. We are here to support your weight loss journey and answer your questions about weight loss prescription drugs. It is approved for use in adults with obesity (BMI ≥30 kg/m2) or overweight (BMI ≥27 kg/m2) and at least one weight-related condition alongside a reduced calorie diet and increased physical activity. Results from studies that used transgenic GIP-overexpressing mice or that administered GIP to humans show that GIP results in weight loss and improved insulin sensitivity (Hojberg et al., 2009; Kim et al., 2012), suggesting that GIP could be a therapeutic target for obesity. Semaglutide 2.4 mg reduced the physical limitations and improved exercise function compared with placebo (Kosiborod et al., 2023, 2024); semaglutide 1.0 mg delayed the progression of diabetic kidney disease, which is lower than that recommended for people with obesity (Perkovic et al., 2024). The company plans to test orforglipron for maintenance of weight loss in people who participated in another Lilly trial, comparing its drug Zepbound with Novo Nordisk’s Wegovy. It’s a field that’s already undergoing a revolution, with millions of people across the US now using semaglutide and tirzepatide, sold as Wegovy and Zepbound for weight loss (and for diabetes as the better-known Ozempic and Mounjaro). At least a dozen similar experimental weight-loss drugs designed to be taken as pills are working their way through clinical trials, with the most advanced now in the third and final stage of testing. In trial data published last year, retatrutide helped people lose more than 17 percent of their body weight, or 41 pounds, after 24 weeks. It's not the first time the government has floated Medicare coverage of obesity drugs. The first includes those who are overweight, with a body mass index greater than 27 or with prediabetes or established cardiovascular disease. But Medicare coverage could have a bigger impact on who gets the drugs because the program covers about 66 million people, and is the primary source of insurance for people ages 65 and above. AOMs may counter the effects of metabolic adaptation and prevent weight regain. Additionally, drugs targeting hunger or satiety signaling have been actively studied and have shown increased adoption by physicians. Keep in mind that obesity is a disease, and no drug can permanently “cure” it. Even when a patient is engaging in exercise and other lifestyle adjustments, medications can help with hunger, cravings, and metabolic preservation. Some patients who are less comfortable with injections may ask about weight-loss pills.