High Cortisol Chad
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I've heard claims that they are supposedly miracle drugs that solve obesity and will change the world (and people are supposed to take them for the rest of their lives).
I myself have never needed, do not need, nor will I need to lose weight, but I am very interested in any remedy that supposedly changes the net human phenotype. My hypothesis, which so far I have not been able to falsify, is that it is not possible to significantly, long-term change the net phenotype by pharmacology, the closest thing are anabolic steroids, but they still can't move someone even just halfway on the normal distribution when it comes to the phenotype associated with building strength/muscle mass. Another example: my grandmother is a very neurotic, anxious, non-energetic person - if she had fresh receptors, and we gave her a reasonably high dose of alprazolam with methamphetamine then for the duration of these drugs she would show a significantly different phenotype of a much less neurotic, anxious and more energetic person, but tolerance forms quickly and these drugs will stop working, moreover, after they are withdrawn from her blood there will be a withdrawal which will completely equalize her net phenotype.
But back to Semaglutide/GLP-1, many of the studies I've seen have been short-lived (in my opinion it takes about 5 years of chronic administration of the substance, the same dose, to be able to assess with high probability whether it works long-term), some studies also use dose escalation which also shortens the time of the study in which the same dose was administered. The longest single study so far (16 weeks dose escalation then 88 weeks of the same dose) shows that there is a rapid weight loss (an average of about 1893 kcal deficit per week), but after 68 weeks there is a reversal of the trend, and they start to gain weight (for the next 36 weeks, that is, until the end of the study, an average of 410 kcal surplus), it does not look promising.
I was curious to know how much % body fat they really lost, because that's the point, no one wants to lose 20 kg of lean body mass and 0 fat, even for the severely obese this is very undesirable, I think everyone will agree that % body fat lost and not % weight lost is the only important thing here. It's known that it's impossible to know exactly what true % bf they started with, because all methods except maybe magnetic resonance imaging are inaccurate, but one can make a reasonably good estimate of the trend in bf loss by the amount of weight lost and waist circumference(which btw is also a very important indicator correlated with insulin sensitivity and desired metabolic changes).
So, using a simple YMCA calculator like this https://planetcalc.com/184/ which did a pretty good job of estimating relative bf% loss/gain for me when I was still exercising a few years ago, I calculated how much the Semaglutide group and the placebo group lost on average.
The Semaglutide group lost an average of 3.631846% bf%, the placebo group lost an average of 2.51376% bf%. This gives a difference of 1.118086% %bf loss between placebo and semaglutide (sic!). Of the weight they lost, the semaglutide group lost 58.217% body fat and 41.783% lean body mass(sic!), you might think well ok that's probably also a lot of water because they are obese, and you know you lose some muscle on a cut, but it turns out that it's not, because the placebo group lost NO lean body mass, what's more they even made a slight recomposition xD which is not surprising because when an obese person starts to exercise (which in this study they did) a slight recomposition is not unusual.
www.nature.com
I myself have never needed, do not need, nor will I need to lose weight, but I am very interested in any remedy that supposedly changes the net human phenotype. My hypothesis, which so far I have not been able to falsify, is that it is not possible to significantly, long-term change the net phenotype by pharmacology, the closest thing are anabolic steroids, but they still can't move someone even just halfway on the normal distribution when it comes to the phenotype associated with building strength/muscle mass. Another example: my grandmother is a very neurotic, anxious, non-energetic person - if she had fresh receptors, and we gave her a reasonably high dose of alprazolam with methamphetamine then for the duration of these drugs she would show a significantly different phenotype of a much less neurotic, anxious and more energetic person, but tolerance forms quickly and these drugs will stop working, moreover, after they are withdrawn from her blood there will be a withdrawal which will completely equalize her net phenotype.
But back to Semaglutide/GLP-1, many of the studies I've seen have been short-lived (in my opinion it takes about 5 years of chronic administration of the substance, the same dose, to be able to assess with high probability whether it works long-term), some studies also use dose escalation which also shortens the time of the study in which the same dose was administered. The longest single study so far (16 weeks dose escalation then 88 weeks of the same dose) shows that there is a rapid weight loss (an average of about 1893 kcal deficit per week), but after 68 weeks there is a reversal of the trend, and they start to gain weight (for the next 36 weeks, that is, until the end of the study, an average of 410 kcal surplus), it does not look promising.
I was curious to know how much % body fat they really lost, because that's the point, no one wants to lose 20 kg of lean body mass and 0 fat, even for the severely obese this is very undesirable, I think everyone will agree that % body fat lost and not % weight lost is the only important thing here. It's known that it's impossible to know exactly what true % bf they started with, because all methods except maybe magnetic resonance imaging are inaccurate, but one can make a reasonably good estimate of the trend in bf loss by the amount of weight lost and waist circumference(which btw is also a very important indicator correlated with insulin sensitivity and desired metabolic changes).
So, using a simple YMCA calculator like this https://planetcalc.com/184/ which did a pretty good job of estimating relative bf% loss/gain for me when I was still exercising a few years ago, I calculated how much the Semaglutide group and the placebo group lost on average.
The Semaglutide group lost an average of 3.631846% bf%, the placebo group lost an average of 2.51376% bf%. This gives a difference of 1.118086% %bf loss between placebo and semaglutide (sic!). Of the weight they lost, the semaglutide group lost 58.217% body fat and 41.783% lean body mass(sic!), you might think well ok that's probably also a lot of water because they are obese, and you know you lose some muscle on a cut, but it turns out that it's not, because the placebo group lost NO lean body mass, what's more they even made a slight recomposition xD which is not surprising because when an obese person starts to exercise (which in this study they did) a slight recomposition is not unusual.
Two-year effects of semaglutide in adults with overweight or obesity: the STEP 5 trial - Nature Medicine
Results from the STEP 5 trial, testing semaglutide as an adjunct to behavioral interventions in adults with overweight or obesity, demonstrate sustained weight loss over a period of 104 weeks.
www.nature.com
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