It gets even thinner: The Ozempic Diet Injection was just the beginning

They lack willpower, they are lazy, they only eat unhealthy things and too much anyway. Overweight people often face such stigmatization. “I used to think so too,” says Ralph Peterli, obesity surgeon and deputy chief physician for visceral surgery at the University Abdominal Center in Basel. “But once you know the science, you change your mind.”

In fact, we now know that metabolism and feelings of hunger and satiety are controlled by neurobiological processes. They cannot be influenced at will. They are programmed into the genes, shaped by the mother’s behavior during pregnancy and influenced by her own lifestyle. “Obesity originates in the brain,” notes Peterli.

And that’s exactly where the diet injections come in that have been hyped as miracle cures for a while: Ozempic and Wegovy with the active ingredient semaglutid. The preparations are seen as a game changer in the treatment of morbid obesity. According to studies, an average of 10 percent of body weight simply melts away. “It’s really amazing how well the drugs work. How some people just stop thinking about food and feel incredibly good as a result,” says Peterli.

For the first time, there is an effective medical weapon in the fight against the widespread disease of obesity and overweight, which affects 42 percent of the population in Switzerland. That is three times as many as thirty years ago. The economic costs of this epidemic amount to eight billion francs per year.

The demand for the funds is high and sometimes leads to bottlenecks. This despite the fact that unpleasant side effects can occur, especially at the beginning of the treatment. Complaints are also made about this on social media, about nausea, vomiting, stomach cramps, and diarrhoea. “These side effects are due to the fact that the active ingredient triggers hormonal signals similar to when we stuff our stomachs with cake at a birthday party,” explains Wolfgang Langhans, emeritus professor of physiologist and behavior at ETH Zurich.

In fact, the drugs actually developed for type 2 diabetes mimic the satiety hormone GLP-1. This is produced in the gut and, if we overeat, in the central nervous system. With the latter, the brain not only registers the signal ‘I’m full’, but the appetite is also lost, you feel uncomfortable, in the worst case you have to vomit.

But apart from the sometimes severe nausea, there are no significant side effects of Semaglutide and the related preparations. On the contrary. A recent study of 17,500 patients found that weekly administration of Wegovy reduced the risk of cardiovascular disease by 20 percent.

Another study showed that the active substance is even good for the brains of overweight people. Obesity leads to decreased insulin sensitivity, which in turn reduces the capacity for associative learning. The active ingredient reverses this after a single dose.

For decades, the road from pharmacological agents to weight loss was paved with “disasters,” as Wolfgang Langhans puts it. The recent case of rimonabant, an active ingredient that makes people want to eat, was sensational and tragic. But, “The drug has taken away not only patients’ desire to eat, but also some of the desire to live,” says Langhans. After reports of suicides in Great Britain and suicidal thoughts, the drug was withdrawn from the market in 2008 after a short time.

So it’s not surprising that pharmaceutical companies are now rubbing their hands — and working in a gold rush mood on even more effective weight loss injections. This includes the Eli Lilly group with the active ingredient Tirzepatide, which leads to an average weight loss of 16 percent, according to a study published in June in The Lancet. The highlight: Tirzepatide has a double effect: it not only imitates the satiety hormone GLP-1, but also the intestinal hormone GIP. The preparation, which goes by the trade name Mounjaro, has been approved in Switzerland for adults with type 2 diabetes mellitus since November 2022, but is not yet available.

Newer preparations even have a triple effect: they not only stimulate the receptors for GLP-1 and GIP, but also those for glucagon. In a study just published in the renowned “New England Journal of Medicine,” a preparation called Retatrutid, also from Eli Lilly, achieved a whopping 24 percent reduction in body weight.

“As far as I know, it has not yet been clarified why this triple agonist works so well,” says Langhans. But he has a hunch: glucagon plays a role in how many of the calories you eat are simply lost as heat instead of going to fat stores. If the proportion of heat is increased, one can – simply put – eat more without gaining weight.

In addition, a slimming capsule containing the drug candidate offorliprone will soon enter the final clinical phase. Instead of being injected, the drug can be swallowed.

Obesity expert Ralph Peterli is impressed by the numbers of the new preparations: “These drugs come very close to surgical procedures such as a gastric bypass or gastric sleeve.” With these surgeries, body weight can be reduced by 25 to 30 percent.

In addition to GLP-1 drugs, some obesity researchers are looking at the hormone leptin. This reports fat status to the brain and helps the satiety hormones develop their function. Leptin resistance can develop in obese people. The result: hunger is not satisfied, even if the fat stores have long been full. Research shows that giving the hormone amylin can partially reverse this nasty resistance in overweight people.

Instead of the satiety mechanisms, some scientists devote themselves to starvation. The AgRP neurons play a “fascinating role in the brain” for this agonizing feeling, as Wolfgang Langhans says. Experiments on mice have shown that if you switch off these nerve cells, the animals starve.

As researchers recently discovered, diets can profoundly disrupt the way these neurons communicate. Diet mice sent out more hunger signals. That also remained the case after the diet. If this could be prevented, it could spell the end of the dreaded yo-yo effect. “Our long-term goal is to find therapies for people that can help maintain their body weight after dieting,” lead author Henning Fenselau of the Max Planck Institute for Metabolism Research is quoted in a press release.

While all the new drugs and starting points in the fight against the global obesity epidemic sound extremely promising, some researchers urge caution. For example, the American psychiatrists Cynthia Bulik and Andrew Hardaway. In the journal ‘Science’ they recently warned that effective diet drugs can cause people to stop exercising because they are slim anyway. Overall, however, this would be detrimental to health. Other experts fear that the stigma of being fat could only get worse as societal pressures to be thin increase.

According to Ralph Peterli, a first and important step would be for Switzerland to recognize obesity as a chronic disease, as the World Health Organization did more than 20 years ago. The association “Allianz Obesity Switzerland” also fights for this. Among other things, he calls on politicians to recognize obesity as a disease in itself and to expand the criminal law against discrimination in such a way that obese people are better protected against stigmatisation. (bzbasel.ch)