You have probably heard these stories: For every man who cuts carbohydrates from the diet and loses 5 pounds, there is a woman who does exactly the same thing and loses only 1. Research confirms this frustrating data – diet and exercise often bring much better results to men than to women when it comes to weight loss.
Therefore, the results of recent clinical tests surprised – and animated – a lot of people: in study after study, the Injectable GLP-1 weight loss medications appear to work better on average in women than in men.
What is not yet known is why. And researchers say that understanding this is critical for doctors to use these powerful medications as effectively as possible for everyone.
The most recent study to identify this effect was presented on Sunday during the annual Congress of the European Obesity Association, and also published in the New England Journal of Medicine.
This was the first direct comparison between the injectable and tirzepatidal injecting drugs – sold with the trade names Wegovy and Zepbound, respectively, for weight control. About 750 people with obesity were randomly divided into two groups. Half received the maximum dose of Wegovy that could tolerate; The other half took the maximum dose of Zepbound.
Zepbound is a younger medicine than WeGovy. It stimulates two different intestinal hormones that influence appetite and blood sugar control, while WeGovy acts mainly on only one of these hormones.
Many doctors have already noted that Zepbound seems to be a more powerful medicine than WeGovy, so it was no surprise when this study – sponsored by Eli Lilly, a Zepbound manufacturer – reached the same conclusion. Participants who used Zepbound lost about 50% more weight than those who took Wegovy, making Zepbound the superior medication in terms of weight loss.
A curious data of the study is that all participants, on average, lost a little less weight than observed in other clinical trials with the same medications.
The researchers say this result was pulled by men, who lost about 6% less weight than women . About 35% of participants in this study were men, while in previous studies this number ranged from 20% to 25%.
“Because this works best in women, honestly I can’t say, but it’s great,” said Dr. Louis Aronne, director of Comprahensive Weight Control Center at Weill Cornell Medicine and study leader. “This has been observed repeatedly.”
For example, in a long -term follow -up of a study that compared semaglute with placebo, women who used semaglutado for two years lost an average of 11% of the initial weight, while men lost an average of 8%. In tirzepatidal studies compared to placebo, women even lost up to 28% of the initial weight, while men lost up to 19%.
Unraveling the specific effects by sex
“There may be several reasons for this, covering several biological and cultural aspects ”Said Dr. Melanie Jay, an obesity expert and a medical professor at Grossman School of Medicine at New York University.
The first hypothesis is related to the dosage of medicines. Women usually weigh a little less than men, but they receive the same doses, so they may be receiving a higher “relative” dose for body size. “Maybe they are getting a higher dose,” said Jay.
It may also have to do with how women store fat. Jay explained that women tend to have more skin fat, that is, under the skin, while men accumulate more visceral fat, which is around the internal organs, such as the liver. Perhaps the medications are more effective in one type of fat than in the other.
In addition, women face more social pressure To be thin, which, according to Jay, can increase the motivation to continue taking medicines – which are not always easy to use.
Jay said she has already observed this in her own clinical practice. Women seem more willing to tolerate and deal with the significant side effects of these medicines, which may include frequent nausea, vomiting and constipation.
“Some men tell me, ‘I can’t deal with constipation or nausea,’ while women often find out how to overcome these effects,” Jay said.
She commented that side effects tend to improve over time as people learn to feed differently and begin to practice more exercises.
Role of estrogen in weight loss
One of the most interesting clues to explain why women benefit more from LPG-1-based drugs is related to estrogen hormone, which is more abundant in women than in men.
Dr. Karolina Skibicka is a professor of molecular medicine at the University of Gotemburg, Sweden, and has a laboratory at the Penn State University Nutrition Department. “In general, I am a neuroscientist interested in gut communication and brain,” and that’s how she began to study LPG-1, an intestinal hormone that also acts in the brain.
Skibicka explains that scientists have known for about 30 years that estrogen has a role in metabolism, but did not understand exactly how. His research with mice has shown that estrogen interacts directly with GLP-1 and other intestinal hormones, making them more potent in the brain.
Several studies have shown that by injecting GLP-1 along with estrogen into rats, “you observe a much stronger effect in many ways, such as dietary behavior, motivated behavior and other LPG-1 actions,” she said.
It is possible to test this interaction in another way, he added. If you block estrogen action with a chemical inhibitor, the effect of LPG-1 also decreases.
“If we remove estrogen, the effect is reduced, then the animals will eat a little more, or the GLP-1 is simply not so effective in suppressing diet or food reward behavior, perhaps more specifically, when we take off estrogen,” she explained.
Estrogen seems to amplify the effects of LPG-1 by increasing the number of receptors-which we can imagine as boat docks-on the surface of the cells, where this intestinal hormone can bind. In many tissues, she said, cells have receptors for both estrogen and LPG-1. “So you end up having an amplified effect also inside the cell.”
Although all these theories are interesting, so far they are just founded hypotheses.
An incentive for further research
“We are dealing with a scarcity of data, even in relation to the basic data we have about what GLP-1 does,” said Skibicka. “Clinical studies usually do not investigate or confirm why they see this difference.”
Both Jay and Skibicka claim that differences between sexes are usually little explored when it comes to medicines, and GLP-1-based medicines are no exception.
In studies that have sex -separated data, women may lose between 50% and 90% more weight than men, but also seem to report more gastrointestinal side effects, according to Skibicka. Men seem to get more cardiovascular benefits with these medications.
Although most studies do not find negative impact of GLP-1 medicines on mood, some indicate that this may vary between sexes, with women being more likely to experience depression while using these medicines compared to men.
Understanding the impacts of these differences between sexes can be important for all patients.
If estrogen influences the intensity of the effect of drugs, this may have implications for treating women before or after menopause, as estrogen levels fall with age. It can also affect the effectiveness of LPG-1 medicines in women who make hormone blocking therapies after breast cancer, for example. In addition, it can lead to the development of strategies to help those who do not respond well to treatment – people who cannot lose weight with their medications or who stop losing weight before achieving their goals.
Jay said that understanding the mechanisms behind the differences between sexes can also help in adherence to treatment.
“I think this information is really important, because there may be something we can manage with men to enhance the effect … or we can adjust the dosage,” said Jay. “Men and women have different biologies, and we can’t always treat them the same way.”
This content was originally published in popular weight loss medicines have more effect on one sex on CNN Brazil.
Source: CNN Brasil
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