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Ozempic And Wegovy: What To Know About Semaglutide Weight Loss Drugs

A new class of weight loss drugs on the market have been making waves since they were authorized as a treatment for obesity in 2021. Semaglutide injections, which you may know as Wegovy or Ozempic, have become wildly popular over the past several months, thanks to the buzz they’ve received from TikTok influencers (and rumors of use among some celebrities).

The prescription injections were introduced as a diabetes treatment in 2017, but people soon realized that the medications — which help people with diabetes to manage their blood sugar levels — also led to significant weight loss in people with obesity who’d struggled to lose weight with other treatments.

From there, interest in the drugs grew, and after clinical trials confirmed what people suspected — that semaglutide injections help people lose weight — demand soared, so much so that pharmacies across the country are experiencing shortages in both Wegovy and Ozempic. Obesity specialists understand the hype; this kind of prescription weight loss medication has been a long time coming.

“For those of us who treat obesity, this is a game-changer we’ve never seen before,” said Dr. Dan Azagury, a bariatric surgeon at Stanford Health Care. “This is the first time ever that we have really effective drugs to treat obesity.”

Obesity is one of the most common chronic health conditions in the United States, but until recently, we haven’t had very effective drugs to address the health complications it’s commonly linked to, such as high cholesterol and high blood pressure. Aside from lifestyle changes like diet and exercise, the go-to intervention for obesity has been surgery (think: gastric bypass or the duodenal switch).

According to Azagury, many obesity specialists noticed that, in the wake of receiving bariatric surgery, many patients were suddenly no longer diabetic. Upon investigating the reason for this, researchers identified new gut hormones, including one called glucagon-like peptide (GLP-1), that reacted to food going into the gut.

Further testing revealed that GLP-1, which increases after bariatric surgery, improves blood sugar levels, and consequently helps with diabetes. “That’s why major diabetes goes away within days of surgery,” Azagury said.

After this discovery, pharmaceutical companies set out to form a diabetes drug that could activate those GLP-1 receptors. That’s what led to the development of semaglutidea synthetic compound that mimics the effects of GLP-1 ― and later the semaglutide-based diabetes drug Ozempic, which got approval from the Food and Drug Administration in 2017.

The other key finding about GLP-1: It slows down digestion and reduces food intake, according to Dr. Janelle Duah, a Yale Medicine internist. This is why Ozempic, which is intended for diabetes, has been and continues to be prescribed off-label for weight loss, Azagury said.

The weight loss effects of GLP-1 (which are revved up through semaglutide), combined with the wild demand for Ozempic, drove the drug manufacturer, Novo Nordisk, to create a very similar drug specifically for weight loss: Wegovy. Essentially just a stronger dosage of Ozempic, Wegovy got FDA approval in June 2021.

Who’s a candidate for the medications?

Wegovy, a once-a-week shot, is for adults who have a body mass index over 30, or who have a BMI above 27 with at least one weight-related health issue (think: high blood pressure, diabetes or high cholesterol). It’s also meant to supplement physical activity and dietary changes, which is why obesity specialists like Azagury recommend that patients work with a comprehensive team of providers, including dietitians and therapists, if they can afford to. Patients can get the prescription through their primary care doctor, too.

Many people find that the injections help them feel fuller longer and reduce sugary cravings. It “makes them crave protein and fiber more — thus helping them stick to diet changes that can further enhance their weight loss,” Duah said. Some people say it also reduced their desire to drink alcohol, and helped them to get better sleep.

Ozempic is approved for Type 2 diabetes, not obesity or weight loss, although people are getting it off-label for weight loss purposes. It’s entirely legal for doctors to prescribe meds off-label, but this is likely adding to ongoing drug shortages — which is a major issue for people with diabetes who can’t get hold of the medications.

Obesity doctors are excited that there’s finally a medication to help people, but there are some barriers and side effects to note.

What’s the overall take on these weight loss medications?

Obesity doctors are thrilled. Often, people retain weight because of health problems out of their control, not for lack of willpower or discipline. Many patients with obesity have tried it all, only to see minimal results. “Now we have something to help them,” Azagury said.

According to Duah, the recent surge in prescriptions, for the most part, is for good reason. “It is by far the most efficacious weight loss medication on the market, with users losing up to 20% of their starting body weight,” Duah said.

And even though interest in these drugs is soaring, Azagury thinks they can help still more people. The original class of obesity drugs from the 1960s and ’70s had nasty consequences and likely soured many people on the whole idea. It might take some convincing for more people to accept that there’s finally an effective drug for weight loss available, Azagury said.

There’s also the issue of cost. These drugs aren’t always covered by insurance, Azagury said, so it can get expensive (to the tune of $1,500 to $1,800 a month). “That is the biggest challenge people will face,” Azagury said. “It’s FDA-approved; that doesn’t mean insurance is going to pay for it.”

According to Duah, this is one of the main reasons providers end up prescribing Ozempic instead. Unlike Wegovy, Ozempic is often covered for diabetes or insulin resistance, so patients looking for semaglutide injections can get access to them at a reasonable price.

There are some risks associated with semaglutide injections

As with any drug, there are risks — but the injections are surprisingly well tolerated, Azagury said. The most common side effects are gastrointestinal issues, like nausea, vomiting, constipation, gas and heartburn. These GI-related side effects should subside as your body gets used to the injections; until then, they can mostly be handled by eating smaller, more frequent meals or taking over-the-counter medications like bismuth subsalicylate or heartburn relief tablets, Duah said. (If the side effects persist, be sure to talk to your doctor about finding relief or other, more tolerable options.)

In rare cases, semaglutide injections can lead to thyroid tumors, which can be cancerous. Other potential serious side effects include pancreatitis, gallbladder problems, low blood sugar, kidney issues, allergic reactions and depression. The injections also shouldn’t be used with other drugs that contain semaglutide or that target GLP-1 receptors.

We’re still learning about long-term side effects, since the drug is relatively new. The injections aren’t a quick fix, and most people will have to stay on the medications for at least a year (and likely longer) to meet their weight loss goals and improve their health, according to Azagury. One study found that many people who stop taking the medications rapidly gain the weight back, supporting the growing belief that the injections are meant to be taken for the long haul.

Other than a slightly higher risk of gallstones (which is common with many types of rapid weight loss), we haven’t seen any long-term effects with liraglutide, a similar drug that’s been on the market since 2010. Azagury expects the same will be true with semaglutide-based medications, given their similarity ― but, of course, time will tell.

If you’re interested in semaglutide injections, talk to your doctor. Understand the risks and benefits, and keep in mind that due to inflation, supply issues and growing demand, these drugs tend to be back-ordered — often for the people who need them most. Hopefully, supply will ramp up soon and more insurers will cover the cost. That, Duah said, will help more people get the drugs at a fair price.

“If insurances covered weight loss medications like Wegovy and supply was increased, we wouldn’t be seeing these issues with keeping Ozempic stocked on our pharmacies’ shelves,” Duah said.

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Type 2 diabetes drug Ozampic is facing shortage after approved by FDA as weight loss drug Wegovy

Monday, January 16, 2023 1:57AM

Demand for a diabetes drug is on the rise, but the reason for that demand is being called into question.

The drug semaglutide was initially marketed under the name Ozempic to manage type 2 diabetes, but last year, it was approved by the FDA to be used for weight loss under the name Wegovy.

But now, the drug manufacturer Novo Nordisk is struggling to meet demand, which doctors say is creating a problem for type 2 diabetes patients.

RELATED: National Diabetes Awareness Month: Knowing signs and symptoms

“Our patients with diabetes are struggling just to get their medications to control their blood sugars and so we’re having to substitute other medications, increase their insulin requirements. People are gaining weight back from not being on these medications and so it really is becoming a problem for our patients that are dealing with type 2 diabetes. But then again, there is an epidemic of obesity, as well and we need to treat the obesity to prevent the diabetes in the first place,” said Dr. Disha Narang.

According to the CDC, more than 37 million Americans have diabetes 90% to 95% of them have type 2 diabetes.

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An Effective Obesity Drug Has Now Been Approved for Teens

Photo: Shutterstock (Shutterstock)

The Food and Drug Administration has recently expanded the eligibility of an effective obesity drug known as Wegovy to children as young as 12. In a clinical trial, children who took Wegovy lost far more weight than those who took a placebo. The label expansion is the latest success for this new generation of obesity treatments, though the drugs themselves continue to be in short supply and expensive without insurance coverage.

The FDA approved Wegovy in June 2021 for adults with a BMI over 30 (the definition of obesity) or with a BMI over 27 and at least one possibly weight-related condition, such as high blood pressure. It was the first new obesity treatment approved in seven years. However, the active ingredient of Wegovy, called semaglutide, had previously been approved in a lower dose formulation by the FDA for type 2 diabetes in 2017, sold under the brand name Ozempic. Both Wegovy and Ozempic are made by the Danish pharmaceutical Novo Nordisk.

In the major randomized and controlled clinical trials that led to Wegovy’s original approval, the once-weekly injectable drug was shown to help people lose an average of 12.4% of their initial body weight over a 68-week period compared to people who received placebo, or about a total 15% weight loss. And Wegovy appears to be just as effective in teens.

According to the results of the company’s STEP TEENS trial, published last month in the New England Journal of Medicine, teens who took the drug lost an average 14.7% of their initial body weight over a year’s time, while those on placebo gained 2.7% on average. The treatment group also saw an average 16.1% loss in BMI, compared to a 0.6% increase in the placebo group. The safety profile of Wegovy seems to be similar in teens. The most common adverse events reported in these trials include nausea, vomiting, and diarrhea, which often appeared early on in treatment as people gradually increased their dosage and waned over time. The rate of discontinuation, or people who decide to stop taking treatment, was low and similar across both groups (around 5%).

Obesity rates have continued to increase in the U.S. and many parts of the world over time, including among teens and young children. These trends only seem to have accelerated during the covid-19 pandemic. And though there remains much debate over the exact health effects of obesity, childhood obesity is thought to raise the risk of serious health problems later in life, such as type 2 diabetes.

“The prevalence of teen obesity in the U.S. continues to rise, affecting teens and their families. Now, more than ever, we need new options to support teens,” said Aaron S. Kelly, co-director of the Center for Pediatric Obesity Medicine at the University of Minnesota and one of the STEP-TEENS study authors, in a statement released last week by Novo Nordisk following the FDA’s decision. “This FDA approval offers an additional tool to address this serious, chronic, progressive disease.”

Up until now, medications have been modestly effective at best in helping people lose weight, or have come with dangerous side-effects, such as stimulants that can cause an unhealthy dependence. And while a balanced diet and exercise is healthy for many reasons, people generally do not achieve and maintain significant weight loss through lifestyle changes alone. Many, but not necessarily all, experts agree that semaglutide represents the first in a class of drugs, known as incretins, that can lead to sustained and safe weight loss, along with many other possible health benefits.

At the same time, Wegovy has been in short supply since its debut, due to unexpected demand and production issues last year that caused the temporary shutdown of one of Novo Nordisk’s key manufacturing facilities. These shortages have likely led to an increase in off-label prescriptions of Ozempic, which is now also in limited supply. At least some patients have complained that they’ve been denied Ozempic for their previously existing diabetes as a result.

Novo Nordisk has claimed that these supply issues will be cleared up by early next year. But even if that happens, Wegovy and similar drugs expected to be approved soon will remain out of reach for many people, due to their hefty price tag. Obesity drugs in general aren’t eligible to be covered by Medicare currently, and many private insurers have been reluctant to cover Wegovy so far. Without insurance, Wegovy can cost upwards of $1,500 a month, and it’s likely that many patients will need to keep taking it in order to maintain their weight loss.

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5 Weight Loss Tips Obesity Doctors Recommend Before Trying Semaglutide

  • Semaglutide is a medication that can help people lose weight when other strategies haven’t worked.
  • Obesity doctors recommend starting with lifestyle changes like diet and exercise, or combining them. 
  • Other factors in weight should also be assessed first, including other health conditions and medications. 

The weight loss drug semaglutide has been called a “game changer” for significant, sustainable weight loss in instances where more traditional lifestyle changes have failed to produce lasting changes, according to research. 

Designed to treat diabetes, the medication was approved in June 2021 to treat obesity, quickly selling out. 

It works by mitigating hormonal and metabolic changes that typically make long-term weight loss difficult, according to Dr. Rami Bailony, an obesity medicine specialist and CEO and co-founder of the obesity management platform Enara Health. 

“It’s not a shortcut. What is does is make it so your biology rewards you instead of tries to fight you,” Bailony told Insider. 

Most patients considering semaglutide have repeatedly tried to lose weight by other means, which can result in feelings of guilt, shame, or feelings of failure, endocrinologist and obesity medicine specialist Dr. Scott Isaacs told Insider.

“If someone is working really hard at losing weight and not getting anywhere, that’s the time when you’d want to see a specialist,” he said.

You can get the best weight loss results by working with a qualified obesity medicine doctor to assess all your potential treatment options, including lifestyle changes and other medications or conditions, before trying semaglutide, according to Bailony and Isaacs. 

A sustainable diet is often the first step for healthy weight loss

The vast majority of patients requesting semaglutide or other weight loss medications have repeatedly tried different weight loss diets without success, the doctors said. 

While many restrictive weight loss diets can work for a few weeks or months, people rarely stick to them over time and regain the weight (and sometimes more), research suggests.

“Anything you do temporarily, you’re going to get temporary results,” Isaacs said. 

Isaacs recommends a reduced-calorie Mediterranean diet for health benefits like lower risk of disease — it’s flexible,  allows enjoyable foods, and is rich in nutritious leafy greens, whole grains, and healthy fats.

But it can be tricky to lose weight and keep it off no matter how healthy your diet, because your body will often adjust hormones and metabolism in an effort to keep your weight stable, known as your weight set point. 

“We often think of weight loss as an equation, but weight loss is more like a tug-of-war. You’re pulling, and eventually your weight set point will realize and start pulling back,” Bailony said. 

Exercise is helpful for weight maintenance

While working out is commonly suggested for weight loss, research now indicates that exercise isn’t very effective for significant, long-term weight loss, since the body can adapt by burning fewer calories over time.

However, exercise is great for overall health and can also build and maintain muscle mass to keep your metabolism strong, especially if you do resistance training. 

“Exercise doesn’t help much with initial weight loss but it’s very important to keep it off,” Isaacs said. 

Check your medications — some can cause weight gain

As many as 20% of Americans may be on medications linked to obesity, research suggests. 

The most common ones include: 

Prioritizing sleep can help you reduce appetite and cut calories 

Getting at least 7-9 hours of sleep per night is an underrated way to help manage weight, Isaacs said.

Sleeping well may significantly reduce your calorie intake, according to one study. 

Get tested for underlying conditions that may interfere with weight loss

Other medical issues can contribute to or complicate obesity, including Cushing syndrome, hypothyroidism, and metabolic disorders.

Treating underlying conditions may not entirely resolve weight gain, but it’s important for overall health and wellbeing, Isaacs said. 

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Wegovy Weight Loss Drug Approved—So What’s Next?

In early February this year, on her YouTube channel “The Hangry Woman,” Mila Clarke Buckley shared her positive experiences taking Ozempic, an antidiabetic medication taken via weekly subcutaneous injection that was first approved by the Food and Drug Administration in 2017.

After two months on it, she recounted, her too-high average blood sugar level (the defining characteristic of diabetes) had steadily declined, her constant and intrusive cravings for food had gone away, and she began to lose weight consistently. But she also, like many users, experienced a week or so long bout of gastrointestinal symptoms like nausea and constipation once she moved up to a slightly higher dose, which was almost enough to make her stop taking the drug. Buckley stuck through the initial turbulence, though, and in a six-month update video, she called it a wonder drug that finally helped her lower her blood sugar—a years-long frustration that she had discussed in earlier videos. In the comments of both her videos were curious onlookers and Ozempic users who backed up her claims of newfound success in managing their diabetes and losing weight.

“After I started taking it, it was almost immediate. I dropped like eight pounds within two months doing nothing differently. So for me, this was awesome, because I’ve always had trouble with this,” Buckley, an author, speaker, and blogger who largely talks about her experiences with diabetes on her channel, told Gizmodo over the phone. “But it’s really interesting that it’s working in this way. Both for weight loss, which is always something that I wanted for myself—my doctor’s never said that I have to lose weight—and then to also have it be something that was helping with my diabetes management.” 

Buckley’s review would soon be relevant to an even greater number of people than the 34 million Americans currently thought to have diabetes. Days after her latest video, Ozempic’s makers, Novo Nordisk, obtained approval from the Food and Drug Administration to sell a new, higher dose version of the drug called Wegovy—one explicitly meant to help people with obesity, long since (and more controversially as of late) defined as having a body mass index over 30, lose weight.

Scientists and doctors have praised the active ingredient in both drugs, known as semaglutide. They’re gone as far as to call it a “game-changer” that could usher in a new era of obesity treatment, both because it’s helped people lose considerably more weight than past remedies and because it seems to work on several aspects of our biology linked to obesity, like our metabolism.

Yet, there remain many hurdles standing in the way of its potential, from whether insurance carriers will even cover it to the unknown long-term risks of a treatment that’s likely to be needed for a lifetime. Additionally, some activists and experts question the inherent value of antiobesity drugs and worry about the floodgates of medical fatshaming and pharmaceutical profiteering that Wegovy’s approval will open up.

Semaglutide belongs to a class of drugs known as GLP-1 agonists, GLP-1 standing for the hormone glucagon-like peptide 1, which helps regulate many bodily functions. One of these roles, according to Donna Ryan, a longtime obesity researcher and professor emerita at the Pennington Biomedical Research Center in Louisiana, is being part of the natural balancing act that is digestion and metabolism.

In the pancreas, for instance, it stimulates insulin production when blood sugar spikes, which stabilizes blood sugar levels. In the stomach, it slows down the emptying of food and decreases stomach acid production, leading to the sensation of fullness. And in the brain, it tamps down our appetite and cravings between meals. Because GLP-1 drugs resemble GLP-1 molecularly, they essentially boost the body’s supply of it; but they also stick around in the body for longer.

“The drugs differ from native GLP-1 in that they have modifications to make them last longer—native GLP-1 only has a half life of 1-2 minutes, while Ozempic has an over 150 hour half life,” Ryan, who has received consulting fees and other financial payments from Novo Norodisk, told Gizmodo in an email.

By amplifying GLP-1, you can help rebalance the biological process that’s gone awry in most people with diabetes, specifically when it comes to insulin. (People with type 1 diabetes no longer produce insulin, but those with type 2 and latent autoimmune diabetes can continue to produce it until their condition progressively worsens.) And because some of these metabolic problems arise in people with obesity, itself a suspected risk factor for type 2 diabetes, the hope is GLP-1 drugs will repair these problems found in people with obesity, too.

What’s made semaglutide so tantalizing to researchers isn’t just the biology behind it but the actual results. Earlier this year, Novo Norodisk published the first of several double-blinded, placebo-controlled, and randomized large trials testing out semaglutide for people with obesity. Compared to those on placebo, with both groups given standard counseling on dieting and exercise, people taking the drug—injected once weekly just under the skin—lost substantial amounts of weight. In one of the pivotal trials reviewed for FDA approval, the average weight loss from a person’s baseline was around 15% over 68 weeks.

Like Ozempic, Wegovy is taken via a weekly subcutaneous injection in gradually increasing doses to help users adjust. It’s formally approved for people with obesity or people with a BMI over 27 and at least one suspected weight-related condition, and it’s the first new weight loss drug approved since 2014. But even that undersells how difficult it has been to find any treatment capable of helping people lose weight and keep it off.

Exercise is one of the best things you can do to have a long, healthy life, for instance, but it’s not a major driver of weight loss. Eating healthy is great, too, but even with sustained changes to your diet, it’s notoriously difficult to maintain long-term weight loss. And most medical treatments now marketed for weight loss only provide a modest boost, if any at all, while past treatments like Fen Phen and 2,4-Dinitrophenol (DNP) were pulled from the market for their dangerous, sometimes fatal side effects (DNP in particular could cause heat stroke by raising a person’s core body temperature too high). The most effective bariatric surgeries help people lose 20% to 30% of their original weight on average, but they are often an expensive and life-altering option that only a small percentage of those eligible for it actually take.

“[The results] were very impressive—it’s not something that any of the other drugs have gotten close to. So there’s really very strong reason to think about using this kind of drug as a primary form of weight loss,” Clifford Rosen, one of the editors at the New England Journal of Medicine who co-authored an editorial discussing Novo Nordisk’s research on semaglutide, told Gizmodo by phone.

Rosen, who is also director of clinical and translational research at the Maine Medical Center Research Institute, added: “After the editorial came out, I got a note from one of my physician colleagues who said she lost like 35 pounds with it, that it’s a miracle drug.”

On paper, Wegovy does seem to be the sort of miracle people worried about their weight dream about, particularly in the wake of scolding media coverage and research telling us that people have gained weight during the covid-19 pandemic. Even before the pandemic, it’s estimated that about 42% of American adults were obese from 2017 to 2018. In reality, though, it’s likely to be a more complicated bargain.

For one, there’s the problem of medical coverage. Traditionally, despite the possible health benefits, approved weight loss treatments are considered cosmetic, meaning that Wegovy wouldn’t be covered through basic insurance plans provided by employers or by the government via Medicare and Medicaid. And without coverage, Wegovy is expected to cost somewhere between $1,000 and $1,500 a month out of pocket, or somewhere around one-fifth of the median American’s household income annually.

On their website, Novo Nordisk is now offering potential patients coupons and other ways to save on out-of-pocket costs. It’s also reportedly doing a full court press in trying to convince private insurers and third party pharmacy benefit managers that Wegovy should be considered an essential treatment just like other medications taken for chronic conditions, including type 2 diabetes. But it’s not clear whether these efforts will bear fruit.

Of the several major insurers in the U.S. that Gizmodo reached out to regarding Wegovy, only Cigna responded. Soon after its approval, Cigna announced that its health services company Evernorth would include Wegovy for coverage in its specialty weight management program (the program is offered through Express Scripts, the pharmacy benefit manager that merged with Cigna in 2018). But it’s a plan that employers would have to agree to provide to employees and that employees would have to buy into first for them to gain access to Wegovy with a doctor’s prescription. Cigna’s own baseline coverage of Wegovy is up in the air.

“As with any newly approved medication, our independent Pharmaceuticals & Therapeutics committee will be reviewing Wegovy and making a coverage determination in the coming weeks,” Cigna said.

The situation looks even more dire for those on public plans. In the very statutes that established the Medicare Part D program in 2006, which provides coverage for prescription drugs, weight loss drugs are considered exempt from basic coverage. Individual Part D providers might still cover Wegovy, but only under enhanced plans, and state Medicaid plans are allowed to cover these drugs if they choose. But under the current law, a representative for Centers for Medicare & Medicaid Services told Gizmodo, basic Medicare plans will not cover weight loss drugs, Wegovy included.

Beyond the financial hurdles, there are the lingering long-term questions about semaglutide left unanswered.

Many common drugs we take, like antibiotics, are only taken for a brief time, until the relevant condition is cleared up. But it’s looking unlikely that semaglutide will be one of those, at least if you want the weight to stay gone. In another trial funded by Novo Nordisk, people who had taken the drug for about 20 weeks and then went off it were compared to those who had kept taking it for the next 48 weeks. While both groups remained at a lower BMI than before they started the trial, those off semaglutide regained more than half of the weight they lost on average, while maintainers continued to lose weight.

Sixty-eight weeks is a decent length for a clinical trial to run, but it still won’t represent the years, possibly decades of time that some users may take semaglutide. And though it was generally well tolerated in trials, with the most common side effects being the sort of temporary gastrointestinal symptoms described by Buckley and other users, there is at least a theoretical possibility of more serious or longer term risks. Acute pancreatitis, or an inflamed pancreas, has been rarely linked to GLP-1 use, which has raised concerns of a possible further risk of pancreatic cancer. And in trials with rats, GLP-1 drugs were found to raise the risk of a relatively rare form of thyroid cancer called medullary thyroid cancer.

There’s also precedent for this issue showing up with weight loss drugs. Just last year, the FDA successfully requested that Japanese pharmaceutical Eisai pull its appetite suppressant drug Belviq from the U.S., after postmarket safety data suggested that those on it were more likely to develop cancer.

There isn’t evidence that any such cancer risk exists with semaglutide specifically. But some researchers have noticed a possible connection between medullary thyroid cancer in people and different GLP-1 drugs. Other research, however, has so far found no connection between pancreatic cancer and GLP-1 use. All GLP-1 drugs on the market, including Wegovy, do warn people to be on the lookout for pancreatitis and warn doctors against prescribing them to people with a family history or genetic mutations linked to a higher risk of medullary thyroid cancer.

“These weight loss studies are powered for FDA approval based on short-term data. And if you really think about it, we haven’t had long-term drugs for weight loss. But now we’re talking five, 10 years for certain drugs. That’s a whole different ballgame. And yes, there may be some off-target effects,” Clifford Rosen said. At the same time, he added, the chances of finding something “startlingly off target” are probably very small, and he points out that some people with type 2 diabetes have been taking these drugs for years now, with no major issues reported.

It’s worth noting that other weight loss aids have carried a risk of abuse. These drugs have typically been stimulants, which can not only reduce appetite but also provide a sense of euphoria that can become addictive. But none of the experts I talked to believed that Wegovy would have a similar risk, at least in the same way that stimulants do. For one, it doesn’t seem to affect mood, and any person trying to take a much higher dose for would probably be dissuaded by the added probability of experiencing nausea and vomiting, Ryan said. She also felt that the possibility of people using it when not indicated, including people with disordered eating patterns like anorexia, was low for the time being, given its current prescription requirements.

“I am sure that people with anorexia might want to take Wegovy, as would people who want cosmetic weight loss but don’t meet BMI criteria, but it would be hard to get it, and no reputable physician would prescribe it,” she said. “In Brazil, the GLP-1 RAs are taken off label for cosmetic weight loss, but this has not occurred in the U.S. The price tag ($1,300 per month) is a deterrent.”

No matter the drug, they all have their side effects and risks and have to be measured against the benefits they provide to see if they’re worthwhile for people to take. The FDA and many experts firmly believe that semaglutide meets that standard by treating obesity more effectively than any prescription drug that’s come along so far.

It’s a framing that presumes obesity and fatness are something to be repaired, though there’s disagreement on what that something is. The current medical consensus is that obesity is a chronic disease caused by a complex mix of not always controllable factors, including our environment and genetics—one that robs people of their good health and quality of life. Much of the general public, meanwhile, might agree that obesity is a serious health problem but still see it as an individual failing of lifestyle and willpower, despite the evidence that shows otherwise. Yet there are other people, including academic researchers and doctors, who are skeptical about both prevailing narratives. And to some of them, Wegovy isn’t a paradigm shift—it’s just more of the same propaganda they’ve seen their entire lives.

“It was immediate, these alarms in my head, because I was like, ‘There’s no such thing as a game-changer drug.’ In the past, with other medications that have been approved for weight loss, they have been extremely harmful, have had serious tolls on people taking them,“ Marquisele Mercedes, an activist in the fat acceptance movement, researcher, and doctoral student at Brown University’s School of Public Health, told Gizmodo by phone. “And pharmaceutical companies are notably shitty, so I was absolutely like, ‘There’s no way this is the whole story.’”

In late June, Mercedes wrote a detailed criticism of Wegovy’s approval and the praise surrounding it. Among other things, she noted that the trials used for approval were funded by Novo Nordisk and that many of the top researchers behind these studies or promoting the success of Wegovy had gotten research funding or outside payments from Novo Nordisk in the past. (Industry-funded research is an all-too-common practice, and these studies tend to provide rosier results than non-industry research.)

Mercedes also pointed out that the company once settled a lawsuit from the federal government and was forced to cough up $60 million over its attempts to downplay the possible risks of medullary thyroid cancer from another of its antidiabetic GLP-1 drugs, Victoza, in its marketing to doctors. (At the same time, FDA had endorsed Victoza for its added benefits in reducing the risk of heart disease and stroke in type 2 diabetes patients.)

Aside from these arguments, the underlying premise of weight loss treatment that Mercedes and others in the fat acceptance and body positivity movements criticize—that it’s something that absolutely has to be treated—may be on shakier ground than most think.

“There’s this assumption that runs so deep—that if you’re fat, it’s going to be bad for your health, end of story. Like it’s not even questioned,” Harriet Brown, an author and journalist who has written about the science of weight loss, told Gizmodo. In the past, she’s argued that diets and other true-and-tired methods of weight loss are both ineffective and counterproductive to helping people stay healthy.

Plenty of people have lamented the use of BMI as a standard measure of health for many reasons. It’s well known, for instance, that two people with the same BMI can have very different types of bodies, depending on how tall they are and how much muscle and body fat they have. But more perplexing is that a higher BMI isn’t always neatly correlated to worse health. At least some studies have shown a so-called obesity paradox, where people who are overweight or mildly obese appear to live longer or have better health outcomes than people at “normal” BMI (people on either extremes of BMI tend to have the worst outcomes).

Some researchers have also argued that while people living with obesity do experience worse health in some ways, much of that harm can be attributed to the weight stigma and discrimination they face from others, including from their own doctors (weight stigma might even keep people from adopting healthy behaviors like exercise). Other studies have suggested that frequently losing weight, only to gain it back, can damage people permanently and could account for some of the health risk linked to obesity.

This debate over obesity and health remains contentious, and there’s a stronger link between obesity and certain health conditions, particularly type 2 diabetes, than there is for others (even so, most people with obesity do not develop diabetes). But it at least brings up the possibility that being overweight or obese in of itself isn’t the death sentence it’s commonly portrayed to be (some researchers have even called for BMI to be abandoned as a primary screening tool for health). And if that’s the case, then maybe Wegovy isn’t the answer to our prayers—not because it doesn’t work as intended, but because it’s trying to solve a perceived crisis of fatness that might not be dire as many think it is.

“My question would be: Does this drug—does it actually make people healthier? And I don’t think we have an answer to that.” Brown said.

Social movements related to fat activism have existed for decades, and as of late, seem to have only gotten more positive attention as concepts like body positivity have become mainstream (if not always productively). But that’s not to say there won’t be people eager for Wegovy. And for many of these potential users, Wegovy won’t just represent a sure-fire way to lose weight. Some obesity doctors and researchers argue that finally having an effective antiobesity drug on hand will help reduce weight stigma by making it clear that obesity isn’t a matter of willpower—it’s a metabolic condition that doctors now have a reliable way to manage.

Raychel Vasseur is one of the first customers of Calibrate, a company aiming to help people lose weight by pairing nutritional and lifestyle counseling with prescription medication, particularly GLP-1 drugs (Donna Ryan is one of Calibrate’s scientific advisors). According to Vasseur, she had been hesitant to take medication for weight loss. But after consulting with her Calibrate doctor, she felt it was the best thing to keep her metabolic problems and overall health under control. She said in an email that it has also helped reduce her cravings for often unhealthy foods, along with the fatigue she regularly experienced after eating them, writing, “I finally feel, for the first time in my life, that I don’t give food power anymore.”

In the months and years to come, Wegovy is likely to be only the first of many newfangled obesity treatments. Various pharmaceutical companies are running ongoing clinical trials of their own GLP-1 candidates, as well as drugs meant to mimic other gut hormones. This past May, Novo Nordisk released the preliminary results from a Phase I trial of semaglutide combined with the amylin analogue cagrilintide, which seemed to show an even greater weight loss effect than using semaglutide alone (albeit, with adverse events like nausea, vomiting, and indigestion being more frequently reported for the combination group).

Researchers like Donna Ryan are hopeful that future studies will not only demonstrate that GLP-1 drugs help people with obesity lose weight but also improve other markers of health. To that end, she’s one of many scientists behind the SELECT trial, which is measuring cardiovascular outcomes among overweight and obese people with a history of cardiovascular disease who take semaglutide or placebo.

“One of the barriers to obesity medicine is that we have not heretofore had evidence that weight loss improves hard outcomes (heart attack, stroke, death), only that it improves risk factors,” she said. “That is one thing that has contributed to the popular belief that weight is something that can be easily controlled and that obesity is really the patient’s fault.”

People who join Calibrate can enroll in a year-round program, which currently costs $129 per month or $1,550 per year. However, as part of this program, the company claims it will negotiate with private insurance companies to ensure drugs like Wegovy are covered, though those with high deductibles would still need to reach their out-of-pocket limit. According to Calibrate, it will refund customers if they’re unsatisfied with their insurance coverage.

And for those with Medicare who want Wegovy, that might be less of a problem in the future. This past March, Senators Kevin Cramer (R-ND), Tom Carper (D-DE), and Bill Cassidy (R-LA) reintroduced the Treat and Reduce Obesity Act, legislation that would remove the restriction of Medicare coverage for obesity treatments, including drugs like Wegovy. The bill is a rare example of bipartisanship these days, and it’s gotten backing from a long list of public health and obesity-related organizations. But it’s also gotten support from companies that would stand to benefit from the law, including Novo Nordisk, and two of the three co-sponsors have received significant campaign donations from the healthcare or insurance industry in recent years.

Wegovy may yet be the start of a new golden era for obesity research and treatment. And it may very well improve people’s health with little to no long-term complications, save for long-term weight reduction with continued use. But people like Mercedes and Brown fear what will come next if Wegovy does turn out to be every bit as popular and profitable as they expect it to be (even mediocre weight loss drugs like Novo Norodisk’s Saxenda have made around $1 billion in annual sales recently).

Leaving aside any direct risks from the drug itself, Mercedes brings up the possibility of users going through cycles of losing and gaining weight if they try to stop taking it, or others feeling further stigmatized for not using Wegovy. She also takes umbrage with the idea that simply having more effective antiobesity drugs around will actually make life easier for fat people. She says that treating fatness as a disease, even for the sake of arguing that people’s obesity is not their fault, is still harmful.

“It doesn’t matter, because you’re still pathologizing the condition,” Mercedes said, citing research suggesting that discrimination toward fat people, including from doctors, isn’t necessarily reduced when people believe that obesity is a disease. “So people are not going to experience less stigma just because there’s a medication that proves that their weight is not in their control.”

At the same time, Brown and Mercedes say they don’t begrudge anyone for wanting to take it.

“I totally understand why the idea of weight loss is appealing, and I would encourage anyone to do what it is they feel they want to do. But I would ask them to look at why they want to take this. Do you want to take this drug for the rest of your life, because you believe it will make you healthier? The jury’s out on that, I think,” Brown said. “But people will have other reasons in this fatphobic culture for wanting to live in a smaller body. And how can you not acknowledge that? I’ve been through that whole dieting cycle many times myself. But if health is really your concern, I would say that there are much more productive ways to go at thinking about that.”



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New obesity drug semaglutide is safe and effective for weight loss and diabetes

After learning that the venom of a Gila monster lizard contained hormones that can regulate blood sugar, Daniel Drucker started wondering why. And could the venom somehow help treat diabetes?

Drucker is a scientist and endocrinologist at the University of Toronto who has dedicated his career to understanding the universe of hormones in the body, which do everything from regulating appetite to helping with digestion. His curiosity about the Gila monster led to a call with a zoo in Utah. In 1995, Drucker had a lizard shipped from Utah to his lab and began experiments on the deadly venom.

Ten years later, a synthetic version of a hormone in the venom became the first medicine of its kind approved to treat type 2 diabetes. Known as a GLP-1 (for glucagon-like peptide-1) receptor agonist, the medicine set off a cascade of additional venom-inspired discoveries.

After doctors noticed mice and humans on the drug for diabetes appeared to lose weight, they began to consider its use in obesity science. In June 2021, another effective treatment, this one for obesity, got Food and Drug Administration approval. Called semaglutide and marketed as Wegovy, it also takes its structure from the lizard’s venom.

If this origin story sounds outlandish, consider the history of obesity treatments. Over the years, people have turned to extreme and unlikely interventions to try to lose weight, from jaw wiring, laxatives, and vagotomies to lap band operations and fen-phen, a “miracle” diet drug that was ultimately recalled.

The new treatment — a once-weekly injectable from Novo Nordisk, a Danish pharmaceutical company that has hired many leading diabetes and obesity scientists as consultants — is poised to safely help many people with health-threatening obesity, physicians and researchers say. It may even illuminate some of the mysteries around how appetite works in the first place.

“It’s phenomenal,” says Michael Krashes, a diabetes and obesity investigator at the National Institutes of Health. Semaglutide is “a big step forward — we finally have something that’s reliable and able to produce sustained effects over time,” adds Ivan De Araujo, a neuroscientist who studies brain-gut interactions at Mount Sinai’s Icahn School of Medicine. Neither scientist is affiliated with Novo Nordisk.

Doctors who treat obesity patients told Vox they wished they had a treatment option like semaglutide years ago, and patients described the drug as life-altering.

Yet many people with obesity may not seek out semaglutide, and doctors may not prescribe it to them — not only because of the dangerous history of weight loss medications, but also because of a persistent bias and stigma around a disease that now afflicts nearly half of Americans. Obesity is still widely viewed as a personal responsibility problem, despite scientific evidence to the contrary. And history has shown that the most effective medical interventions, such as bariatric surgery — currently the gold standard for treating obesity — often go unused in favor of dieting and exercise, which for many don’t work.

There’s also a practical challenge: Health insurers don’t typically cover obesity medications, says Scott Kahan, an obesity doctor and professor at Johns Hopkins Bloomberg School of Public Health and the George Washington University School of Medicine. “Medicare explicitly excludes weight medications,” Kahan, who consults with Novo Nordisk, says. “And most insurers follow what Medicare does.”

The new drug certainly won’t be a cure-all for obesity, Krashes adds. “You are not taking a 280-pound person and making them 130,” he points out, though reductions that are enough to improve health outcomes are typical. Drucker, who began consulting with Novo Nordisk and other drug companies after his reptilian discovery, agrees that it’s a starting point for obesity: “It will only scratch the surface of the problem in the population that needs to be healthier.”

But semaglutide is the most powerful obesity drug ever approved, he adds. “Drugs that will produce 15 percent body weight loss — we did not have that before in the medical therapy of obesity.” With additional, potentially more effective GLP-1 receptor agonists coming online in the future, we’re at the beginning of a promising new chapter of obesity therapeutics. A look at the fascinating science of how the medication works could also go a long way to changing how Americans think about this disease.

“We have to thank the lizard for that,” Drucker says.

What semaglutide reveals about weight problems

To understand how semaglutide causes some people to eat less, it’s helpful to understand what hormones do. They’re the body’s traveling messengers: Manufactured in one area, they move to another to deliver messages through receptors — molecules that bind to specific hormones — in distant organs and cells.

The gut makes dozens of hormones, and many of them travel to the brain receptors that either curb appetite or stimulate it, Drucker explains. GLP-1 is one such gut hormone. It’s unleashed in the gut in response to food and stimulates the pancreas to make more insulin after a meal, which lowers blood sugar. (GLP-1 is also made in the brain stem, where it may modify appetite.)

“It sends a signal to our brain that says, ‘You know, we’ve had enough to eat,’” says Drucker.

Enter semaglutide, one of a class of medicines — the GLP-1-receptor agonists — that imitate GLP-1, helping the body lower glucose (in the case of people with diabetes) and, researchers suspect, curb appetite (in the case of people living with obesity who may also have diabetes).

The precise way the drug works on obesity is still unknown, in part because scientists don’t understand exactly how appetite works. But researchers generally agree that the drug harnesses the brain’s GLP-1 receptors to curb food intake. When researchers delete the GLP-1 receptors from the brains of mice, the drug loses its appetite-suppressing effects, says Krashes.

Obesity is “primarily an issue of our brain biology, and the way it’s processing info about the environment we live in,” says Randy Seeley, a University of Michigan researcher focused on obesity treatments, who also consults with Novo Nordisk.

With semaglutide, the idea is that “we’re changing your brain chemistry for your brain to believe you should be at a lower weight,” Seeley added.

This brain-based pharmacological approach is likely to be more successful than diet and exercise alone, Seeley says, because “the most important underlying part of somebody’s weight has to do with how their brain operates,” not a lack of willpower.

Not quite a “game changer”

Some people with a higher body mass index are perfectly healthy and don’t require any treatment. Semaglutide was only indicated by the FDA for patients who classify as clinically obese — with a body mass index of 30 or greater — or those who are overweight and have at least one weight-related health problem.

For the many people who have used it, it has proved safe and effective, according to the FDA. In weight loss clinical trials, semaglutide helped people lose about 15 percent of their body weight on average — significantly more than the currently available obesity drugs and more than enough to improve health outcomes.

The drug’s most common side effects — nausea, diarrhea, constipation, and vomiting — were mostly short-lived. De Araujo is finding that adverse reactions might be caused by how the drug differs from the naturally occurring peptide hormone: The hormone acts mostly locally and degrades quickly, while the medicine works mainly on the brain and is designed to stick around in the body. “That’s where the nausea, vomiting probably derive from,” De Araujo argues.

Patients who have tried semaglutide told Vox that it helped them manage their weight and relationship to food, and that their side effects were manageable and quickly resolved.

Jim Eggeman, a 911 operator in Ohio, said that before taking semaglutide, “I could sit down and eat a large pizza, and now it’s one to two pieces at the most.” He started on the drug for diabetes after a heart attack in December 2019 and lost 35 pounds, bringing his weight to 220.

Paula Morris-Kaufman, of Cheshire, UK, used the drug to address weight gain following cancer treatments. It helped her bring her weight back to a normal range, she says, and curb her habit of compulsive eating. “If you give me a plate of food, I just eat a small portion of it — and feel full really quickly.”

It’s possible that some of the benefits of treatment come in part from lifestyle changes, which were encouraged by the clinical trials. In many cases, patients on semaglutide also switched to a healthier diet when they started on the drug and added exercise to their routines. But study participants taking the drug still lost significantly more weight than those under the same conditions who received a placebo.

The need for additional interventions — like diet and exercise — is one reason why Kahan stops short of calling this drug a game changer. “It’s an incremental improvement” over existing drugs, he says, and it’s still out of reach for many of the individuals who could benefit from it. “The ‘game changer’ description is not appropriate, because many people don’t have access to these medicines.”

A mindset shift

Only about 1 percent of eligible patients were using FDA-approved medications for obesity in 2019, a study showed. The same is true for bariatric surgery, currently the most effective intervention for obesity, which can also drive type 2 diabetes into remission.

“If someone walks into your office with heart disease and you as a physician don’t try to treat it, that’s malpractice,” Seeley says. “If somebody comes in with a BMI over 30 and you don’t treat it, that’s Tuesday.” He thinks some of the hesitancy for treating patients with obesity medications comes from the history of dangerous weight loss drugs.

Ingrained biases about obesity have also made it harder for patients to get access, Kahan says. “Obesity tends to be categorized as a cosmetic issue in health insurance policies,” he says. “In order to get coverage, employers have to explicitly decide to buy a rider and sign a contract to add weight management services and products to their insurance plans.” He’d like to see obesity treatments covered by insurers in the same way diabetes and hypertension drugs are.

That will require a shift in mindset, Drucker says. “We would never blame other individuals for developing high blood pressure or cardiovascular disease or cancer,” he says. It’s widely known that those conditions are driven by complex biological determinants, including genes, as well as environmental factors. “Obesity is no different.”

When Drucker started in endocrinology in the 1980s, he didn’t have many tools to help patients. With the addition of semaglutide, there are multiple surgical options and drugs for obesity and diabetes. The challenge now is helping those who would benefit gain access.

“I would be delighted if no one needed GLP-1 for diabetes and obesity,” Drucker says. That might be possible in a food landscape that didn’t nudge people toward the overeating and poor diet that leads to these chronic conditions. But for now, “we have new options that are safe, appear to reduce complications, and are very effective. … We shouldn’t just throw up our hands and say there’s nothing we can do.”

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Diabetes Medication Semaglutide Reduces Excess Body Fat in People With Obesity

Findings suggest drug has potential to reduce risk of heart disease, diabetes, and stroke.

In adults with obesity or overweight, weekly treatment with the glucagon-like peptide 1 (GLP1) receptor agonist semaglutide leads to reduced excess body fat and increased lean body mass, according to an industry-sponsored study presented virtually at ENDO 2021, the Endocrine Society’s annual meeting.

“Our findings suggest that semaglutide, through body weight loss and improvement of body composition, has the potential to reduce the risk of heart disease, diabetes, and stroke in people with overweight or obesity,” said lead researcher John Wilding, D.M., F.R.C.P., of the University of Liverpool.

Obesity poses many health risks. Excess fat in the abdominal area, particularly fat in and around abdominal organs, also called visceral fat, contributes to major causes of death and disability, including heart attacks, strokes, high blood pressure, cancer, fatty liver disease and diabetes.

The study, called STEP 1, included 1,961 adults with a body mass index (BMI) of 27 or higher with at least one weight-related health condition, or a BMI of 30 or higher, without diabetes. A person is classified as overweight if their BMI is 25 to 29.9, and the range for obesity is a BMI of 30 or more.

The study participants were randomly assigned to inject themselves once weekly for 68 weeks with either 2.4 milligrams of semaglutide or a placebo. Semaglutide, already approved by the U.S. Food and Drug Administration at the lower dose of 1 mg weekly as a treatment for type 2 diabetes, is a synthetic version of the naturally occurring hormone glucagon-like peptide 1 (GLP1). It acts on appetite centers in the brain and in the gut, and produces feelings of fullness.

As part of the study, the researchers used dual-energy absorptiometry (DEXA), a technique that is widely used clinically to assess body composition, to monitor the effects of therapy on total body fat and fat around the stomach area in 140 of the participants.

They found treatment with semaglutide improved body composition by reducing excess body fat, including abdominal fat, and increasing the proportion of lean body mass, or the amount of weight someone carries that is not body fat. The more body weight a participant lost, the greater the improvement in body composition.

In February 2021, the researchers published findings from the STEP 1 trial in The New England Journal of Medicine showing that patients who injected semaglutide lost close to 15% of their body weight, on average, compared with 2.4% among patients receiving the placebo. More than one-third of participants receiving semaglutide lost more than 20% of their weight. Many patients experienced improvements in risk factors for heart disease, blood sugar levels and quality of life.

Meeting: ENDO 2021



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‘Game-Changer’ Drug Promotes Weight Loss Like No Medicine Ever Seen, Scientists Say

In the simplest terms, obesity is the product of a body’s energy output being less than its energy input. But in reality, there’s nothing simple about this complex and mysterious disease.

 

Obesity, which has skyrocketed in recent decades – now defining the body mass of over 40 percent of adult Americans – isn’t just difficult for people to endure and scientists to understand. It’s also incredibly hard to treat.

Beyond commitment to sustained lifestyle changes – healthy eating and exercise, effectively – there are really only two potential options that may help: bariatric surgery and weight-loss medications.

The former is invasive and carries various risks and complications. As for the drugs, they don’t always work, and can have their own adverse effects too.

However, an experimental treatment recently trialled by scientists and detailed in a study published this week could open new doors for treating obesity patients with a weight-loss drug.

In the study, which involved almost 2,000 obese adults across 16 different countries, participants took a weekly dose of a drug called semaglutide, an existing medication already used in the treatment of type 2 diabetes.

A control group took only a placebo, in place of the medication. Both groups received a lifestyle intervention course designed to promote weight loss.

At the end of the trial, the participants who took the placebo lost a small but clinically insignificant amount of weight. But for those who took semaglutide, the effects were pronounced.

 

After 68 weeks of treatment with the drug – which suppresses appetite due to a variety of effects on the brain – participants taking semaglutide lost on average 14.9 percent of their body weight. And over 30 percent of the group lost more than 20 percent of their body weight.

Broadly speaking, this makes the drug up to twice as effective as existing medications for weight loss, the researchers say, approaching the kind of efficacy of surgical interventions.

“No other drug has come close to producing this level of weight loss – this really is a game-changer,” says obesity researcher Rachel Batterham from University College London.

“For the first time, people can achieve through drugs what was only possible through weight-loss surgery.”

In addition to losing weight, participants registered improvements in other areas, showing reductions in various cardiometabolic risk factors, and reporting quality of life improvements.

While the results are compelling, semaglutide dosage for anti-obesity effects does come with some drawbacks.

Mild-to-moderate effects were reported by many participants (in both the semaglutide and placebo groups), including nausea and diarrhoea. While the effects were temporary, they were enough for nearly 60 of participants to discontinue their treatment, compared with just five in the placebo group.

 

At present, the drug requires a weekly injection to work – whereas an oral form of the medicine would likely be preferred by patients.

More significantly, we don’t yet have data on what happened to the participants after the drug regimen ceased at the end of the trial.

For at least one individual, however, who spoke to The New York Times, her weight began to creep up after the trial was over.

“While drugs like this may prove useful in the short term for obtaining rapid weight loss in severe obesity, they are not a magic bullet for preventing or treating less severe degrees of obesity,” says nutritionist Tom Sanders, an emeritus professor at King’s College London, who wasn’t involved with the study.

“Public health measures that encourage behavioural changes such as regular physical activity and moderating dietary energy intake are still needed.”

Nobody would deny the wisdom of that, but if further analysis of semaglutide turns out to be positive, we could also be looking at an important new pharmaceutical option to help combat obesity.

 

And that option might arrive sooner than we think.

The study, funded by pharmaceutical company Novo Nordisk – which sells semaglutide as an anti-diabetic medication – is now being tendered as evidence to international health regulatory authorities, in support of an application to market the drug as an obesity treatment.

The US FDA, along with its counterparts in the UK and Europe, is currently assessing the data.

The findings are reported in The New England Journal of Medicine.

 

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