午夜福利1000集合

For as long as Kimrey Rhinehardt can remember, she has been trying to lose weight. The keto and paleo diets seemed to work鈥� for a while. But when the weight came off, her emotional eating and sugar cravings ruined her efforts.

Rhinehardt鈥檚 battle to control her weight has been frustrating, but for the management consultant from Pittsboro, North Carolina, it is also dangerous. She has high cholesterol, asthma and a family history of breast cancer. Her weight raises the likelihood she will die from one of these risk factors.

Then, six months ago, a doctor prescribed her weekly injections of a new kind of medication, and everything changed. She lost more than 27 kilograms and her body mass index (BMI) dropped from 41 鈥� considered severely obese 鈥� to 32, just over the threshold for obesity. The drug even changed her perspective on food. Rhinehardt isn鈥檛 interested in many of the unhealthy snacks she used to love. 鈥淐ravings for sugar and bread don鈥檛 exist any more,鈥� she says.

This new drug, semaglutide, marketed as Wegovy in the US, was approved last year by the US Food and Drug Administration (FDA). For Rhinehardt, it has been the boost she needed to finally lose the weight she has struggled with for decades. But for some in the medical profession, the hope is that the drug might revolutionise our fight against one of the most prevalent and lethal health problems in much of the world. Not only could it help treat obesity in people finding it hard to lose weight, but it might even be used to prevent the condition in the first place.

Obesity is a chronic health issue that puts people at risk for other chronic conditions, including cancer, diabetes, heart disease and sleep apnoea. It is also the most common health condition in both the UK and US: 28 and 42 per cent of their adult populations, respectively, are obese. In 2016, when the latest figures from the World 午夜福利1000集合 Organization (WHO) were made available, 13 per cent of adults globally were obese, a figure that had nearly tripled since 1975. now live in countries where being obese or overweight kills more people than being underweight.

Obesity on this scale may be a modern malady, but the promises of quick fixes for losing weight have been with us for centuries. In the 1800s, soap and arsenic were touted as good options for those wanting to slim down. By the 1930s, compound that can cause rapid breathing, a fast heart rate and heavy sweating and can, in some cases, prove fatal 鈥� was promoted for weight control. And prior to a US ban in the 1970s, , despite powerful side effects, including the risk of heart problems.

Even drugs approved by the FDA have flopped. Fen-phen, named after the two appetite-suppressing drugs it contained, fenfluramine and phentermine, was considered the star of diet drugs in the 1990s until it was withdrawn from the market because it caused . In 2020, another diet drug, , was pulled from sale when it was linked to a range of cancers, including pancreatic, colorectal and lung.

Despite this chequered past, with obesity rising globally 鈥� coupled with the fact that when people do lose weight, they 鈥� there is still a thirst for medicines that could help.

This is where a hormone called GLP-1 comes in. As food moves from the oesophagus to the gastrointestinal tract, it activates a system of hormones that help control the digestion of food. GLP-1, which is released from the small intestine, is of particular importance. It signals to the pancreas to release insulin, a hormone that allows cells to take up and use additional glucose from the foods we eat, while cutting the amount of the hormone glucagon 鈥� also produced in the pancreas 鈥� which boosts blood sugar levels. Together, this means fewer sugars are left in the body.

People with type 2 diabetes tend to produce insufficient amounts of GLP-1, which can result in too much glucose in the bloodstream. Semaglutide, however, increases the amount of the hormone circulating the body, helping to bring blood sugar levels under control.

Given these effects on the pancreas, semaglutide was originally approved for diabetes in 2019. But during the , participants also saw significant weight loss. That is because GLP-1 slows gastric emptying, and keeping food in the stomach for longer creates a greater feeling of fullness. The hormone also results in nerve signals being sent to the hypothalamus, a hormone control centre in the brain, telling it to reduce hunger. 鈥淧atients benefit because it both decreases the desire to start eating and, when you do eat, you stop sooner because you feel full,鈥� says .

Following these hints that semaglutide might also be useful for those with weight issues, new trials took place with an increased dose to boost weight loss, and the results were dramatic. Almost 2000 people who were obese were given weekly injections of 2.4 milligrams of the drug 鈥� more than twice what the participants in the diabetes trial received 鈥� or a placebo, and they also undertook lifestyle interventions, such as diet and exercise. Those given the drug , on average, around 15 per cent of their body weight during the 68-week trial, compared with 2.4 per cent in the placebo group.

Just last month, another drug that mimics the effects of GLP-1, as well as those of another satiety hormone called GIP, was shown in a large clinical trial to be even more effective. Participants taking injections of the drug called tirzepatide lost 22.5 per cent of their body weight on average.

Experts are cautiously impressed by these results, and semaglutide was , the first weight-loss drug to gain such approval since 2014.

As well as working well compared to a placebo and lifestyle changes, it also compares favourably to other available weight-loss drugs, because it targets a hormone in the body, rather than just targeting the brain, says Wadden. Contrave, for example, is a combination of the antidepressant bupropion and the addiction drug naltrexone. It works on the hypothalamus to help regulate appetite, but it doesn鈥檛 provide the double whammy of satiation on the gut, and people taking it typically lose between 5 and 10 per cent of their body weight. Those taking it also commonly experience dizziness, a dry mouth, insomnia and intense dreams.

Other drugs work by blocking the digestion of fat in the foods you eat, so that about a quarter of it is excreted in your stools rather than being absorbed during digestion. This more primitive method results in around a 5 per cent weight loss and is accompanied by some pretty unpleasant side effects, such as loose stools, oily faeces and incontinence.

With semaglutide, by far the most common issues have been gastrointestinal. Forty-five per cent of trial participants reported nausea and 30 per cent experienced diarrhoea or constipation. Vomiting affected 24 per cent. This can put some people off, says Fatima Stanford at Massachusetts General Hospital. 鈥淲hen you hear that 45 per cent of patients will have nausea, that is high. Some of my patients fear having it and won鈥檛 try the medications as a result.鈥� Another 5 per cent developed gallstones due to the rapid nature of the weight loss, requiring surgery in some cases.

For the most part, however, doctors have been able to mitigate side effects by starting at a low dose and slowly increasing it as the body develops a tolerance and symptoms subside, says Patrick O鈥橬eil, director of the Weight Management Center at the Medical University of South Carolina. Only about 3 per cent of participants dropped out of the trial due to side effects. Still, we don鈥檛 yet have data on any long-term effects.

Lifetime commitment

The hope is that semaglutide could help people like Rhinehardt finally reach a healthier weight and, more importantly, keep it off. In fact, the drug鈥檚 approval seems to be accompanying a shift in the way that obesity is being treated, at least in the US, with the FDA categorising weight-loss drugs differently, says , a endocrinologist at Northwestern University in Illinois.

Semaglutide, for example, is in a new group of drugs called anti-obesity medications that are approved by the FDA for chronic weight management, an acknowledgement that the issue with obesity often isn鈥檛 just losing the weight, but keeping it off. 鈥淭hose of us that work in this field think of obesity as not just about losing weight, but about how we treat the disease of obesity and all the metabolic and health conditions that are associated with it,鈥� says Kushner. Some people may need help keeping the weight off for the rest of their lives.

These drugs are approved for both weight loss and weight maintenance, which means they need to be thought of as long-term solutions for a chronic relapsing condition, says Kushner. Similar to diabetes or high blood pressure medications, if you stop using the drug, the condition is likely to come back. Once people start taking it, they will probably need to do so forever.

Semaglutide is approved by the FDA for people who are obese, with a BMI of 30 or more, as well as individuals with a BMI of 27 and up 鈥� considered overweight 鈥� who also have a weight-related health condition, such as diabetes, high blood pressure, osteoarthritis or sleep apnoea. When prescribed, it should coincide with lifestyle changes like exercise and calorie-restrictive diets, says Kushner. 鈥淥besity is a public health issue that requires a widespread public health response,鈥� he says.

Since semaglutide is relatively new and was only approved for use in weight loss last June, it is too soon to know its true effectiveness. A given the drug or a placebo over two years is already under way. Some of those who work on obesity have been prescribing the drug regularly. So far, anecdotally, 鈥渢he effects from the trial are being reproduced in my patients鈥�, says Kushner.

Even so, not everyone responds in the same way. 鈥淲hile some patients achieve a 15 per cent or more weight loss, some only achieve a 3 per cent reduction,鈥� says Stanford. 鈥淭here鈥檚 high responders and low responders and those low responders may be better suited for some of the more traditional anti-obesity medications.鈥�

Then there is the cost. At around $1500 per month, the drug is out of reach for most people in the US. of the National 午夜福利1000集合 Service in the UK, it hasn鈥檛 yet been approved there.

Heavy cost

Given the global cost of high BMI, estimated at $990 billion per year, a drug that could prevent obesity in high-risk people could be worth the cost. But for insurers to get on board, we must not only be sure of its safety and efficacy, says O鈥橬eil. We will also need to eradicate antiquated stereotypes around obesity. Many still view obesity as a condition caused by a lack of willpower. Research has shown that with obesity in a negative light. 鈥淲e still, as a society, make assumptions about people based on their weight,鈥� says O鈥橬eil. 鈥淭he world can be very cruel to those with severe obesity.鈥�

Perhaps the biggest reason why the US state-funded healthcare programme Medicare and most private insurers in the country aren鈥檛 yet covering the cost of these drugs is due to the sheer number of people who could benefit. 鈥淭he market for these medications is just so big and if we cover them, it could cost a fortune,鈥� says . Even so, it isn鈥檛 out of the realm of possibility. Bariatric surgery is now covered by Medicare at $25,000 per procedure (see 鈥淧ills vs surgery鈥�).

For Rhinehardt, the cost has been the biggest challenge. 鈥淢y [insurance] plan will pay for [gastric] band or gastric bypass surgery twice, but not Wegovy, even with the results I鈥檓 experiencing,鈥� she says. It remains to be seen whether she can scrape together enough cash to stay on the drug that she thinks may save her life. 鈥淚 want to live a long and healthy life, and I have a better shot at both if I achieve a healthy-range BMI.鈥�