* Blood sugar levels (or whatever this is a proxy for)
* Weight
* The changes the GLP-1 Agonists make to the body itself.
While it is simple to say if you reduce the weight, you reduce the blood sugar levels, and so the GLP-1 is unnecessary, you can look at many accounts of using Ozempic where it talks about reducing the "food noise."
That is, Ozempic makes it easier to eat the right things. I'm a "normal weight" through grit, but I don't think my life is better through said grit - in fact, I'd say it's significantly worse. In my earlier life, I was naturally thin, and I can say that my weight increase wasn't a significant change to my diet, nor was my weight loss: I just had to be hungry and irritable more.
So, fundamentally, the cause and effect doesn't matter, because the drug makes it easier to be a more healthy weight and to control the blood sugar.
Yes! I keep trying to explain to folks that this is the benefit of these drugs, they let you keep a healthy relationship with food, maintain "intuitive eating" where you aren't constantly fighting and discarding your hunger signals, and aren't (as) miserable doing it.
I did it the hard way, I wouldn't wish it on anyone.
Obviously we need some more double blind studies dedicated to this class of drugs and Alzheimer's, but this informs the direction researchers and drug companies will likely map out.
Losing weight is still a hard endeavor.
Plenty of people find their appetite capped at a level where the caloric intake will make them skinny. If they don't eat right and exercise, though, it won't necessarily bring them to great health. Like all caloric restriction, you will lose muscle mass if you don't ingest enough protein and perform resistance training, so you could still end up with a suboptimal lean body mass:fat ratio.
>IIRC it increases the effects of a healthy lifestyle change by 15%,
I'm not sure what this means. In the clinical trials for weight loss, semaglutide patients lost 10-15% of their body weight over the trial period, which might be what you mean? The trials don't indicate that this is the maximum, however - people have seen sustained weight loss for periods longer than the trials. Nor did it require people follow a specific diet or exercise plan. Plenty of people lose weight just eating less of what they were already eating - though this is generally not the best way to approach it.
>effect which is lost if you leave it.
Some number of people regain some or all of the weight they lost when going off the medication, but not all. However, the current indication is that people should be allowed to remain on the drug to maintain (generally at a lower dose) indefinitely if they need to. If the safety profile changes, this recommendation might also change.
>The life style change (activity and nutrition) alone is more important, cheaper, and as permanent as you want it to be.
Agreed. I'm someone who was quite fit when younger and let a variety of factors cause nutrition and exercise to fall farther and farther back on my priority list, and so far, tirzepatide has made it much easier for me to prioritize these things and enjoy them. I'm fairly confident once I have spent some time back at a healthier weight and developed long term habits around these things I'll be able to go off of it.
All we need to do is just tell a few million people to lose weight.
If it’s the drug and not the weight loss that lowers Alzheimers risk, then even people who are not overweight might benefit from the drug.
Those choices become easier when you have assistance.