Intermittent (oral) Rybelsus / Semaglutide use in healthy individuals?

Let’s hope that tirzepatide will make semaglutide cheaper :slight_smile:

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Yikes. This is the Finasteride of weight loss medicines!

I am lean but took Sema 0.25 mg sq once to lose five pounds (which happened in a week) then I changed to taking it once every other week at 0.20 to maintain the weight loss. It’s been amazing. I eat less and blood sugars are lower I use it with patients very frequently, even just to lose 5-10 pounds. Many are also on metformin and I’ve been on Rapa for 3+ years.

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I agree. We’ve now used it very extensively with excellent results on glucose,weight, and even BP’s. Main side effect is nausea which is usually transient and tolerable.

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New study:

Amelioration of inflammatory myopathies by glucagon-like peptide-1 receptor agonist via suppressing muscle fibre necroptosis

https://onlinelibrary.wiley.com/doi/10.1002/jcsm.13025

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Since Semaglutide is only dosed once a week, and even doses of 1/10th of the recommended dose can offer big appetite suppressive effects (and, likely, some of the same improvements in insulin sensitivity, although I haven’t seen that studied in non-diabetic, non-obese populations), this drug is actually pretty affordable.

For example, Tailormade compounding pharmacy has Sema + B12 for around $215 for 5 mg. If you’re only taking 0.25 mg once weekly, that vial will last 5 months! Of course, some people will need to titrate up to see benefits, but I have patients (including myself) who stay on the “microdose” of 0.25 mg weekly and see enough appetite suppression to at least maintain weight.

I’d love to see more research on non-obese, non-diabetics taking Sema (or other GLP-1a’s) for “longevity” purposes. It think it could be pretty compelling.

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I hear this a lot from patients considering finasteride or rogaine (for instance) like it’s some terrible thing.
Until I remind patients that this is true of just about any medication (for it to keep working, you have to keep taking it) except in the case of antibiotics to treat an acute bacterial infection, for instance. I wish we had more options for curative meds, but that’s the way it is for now, unfortunately.

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Agreed. The studies went up to 2.4 mg’s but it’s remarkable how many people respond to just a fraction of that dose. This drug definitely needs to be tailored to the individual.

When you think of how many issues just spring from being overweight or obese, it’s a pretty amazing product. There’s some side effects but they can be managed fairly well in our experience.

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I’ve had a great experience with semaglutide for weight loss.

31 y/o (now 32) male, 5’ 10" and starting weight 211 lbs in Nov 2021, 171 lbs as of my last dose. I topped out at 1.25mg subcutaneous weekly (the Ozempic pen allows custom doses by “dialing clicks”), but at least half the weight loss occurred at the .25mg and .5mg doses. I’m sure I could have obtained even more dramatic results at the lower doses if I had been more attentive to improving my diet, but as it was the only real dietary change made was just eating much less frequently and in smaller portions due to the appetite suppression and delayed gastric emptying.

I know there’s a lot of ongoing research with GLP-1s and their effects on fatty liver disease, as well as potentially other positive effects on conditions and diseases mediated by inflammation. I’ve seen my hsCRP drop from 1.36 mg/L to <.3 mg/L while I’ve been on it, and in a few weeks will have some tests that include fasting glucose, A1C, and insulin, which should be interesting.

I was ordering Ozempic from Canada for ~$300 per pen with an rx from a telehealth provider (HelloAlpha). Both the .25/.5mg dose pen (2mg total per pen) and the 1mg dose pen (4mg total per pen) cost the same, so you could reduce cost significantly if using the 1mg dose pen to take a smaller dose. There’s a new 2mg dose pen that could give you even more of the small doses, but that’s not available yet in Canada last I looked. One caveat is that the manufacturer says that a pen should only be used for up to 56 days after the first dose is taken, even if it’s kept refrigerated. Another method might be to just stretch the doses out - it’s labeled for weekly use, but I found that the effects were still quite noticeable out to at least 10 days and somewhat noticeable for 14 days.

I just switched to tirzepatide due to availability and cost. While $300 per pen is much, much cheaper than the US out of pocket price, the $25 per month coupon for Mounjaro is really attractive. The Wegovy shortages have also started creeping over to Ozempic as well, so I figured it was a good time to try Mounjaro.

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Have you tried taking a break from GLP-1 RAs? What was your experience then?
Also how do you compare “GLP-1 RA” v.s. “GLP-1 RA + rapamycin”, in case you take rapa and had an off-period?

I’ve had a couple of involuntary breaks from semaglutide due to logistical issues with orders from Canada, with the longest being about 3 weeks. The effects waned noticeably within 10 to 14 days. My weight loss stalled and even reversed just a bit, maybe gaining 3-4 lbs.

I’ve heard some doctors talk about how it’s possible that one could maintain the weight loss when discontinuing a GLP-1 if you spend an extended amount of time at your goal weight and sort of reset your metabolic “set point.” My breaks were around the 6 month mark while weight loss was still ongoing, so I can’t say what would happen after a longer amount of time at a stable weight. The time on a GLP-1 would also allow you to build some healthier habits and attitudes toward food. However, to my knowledge every GLP-1 trial for weight loss has shown that on the whole, patients will regain a significant amount of weight if they discontinue the med, so a lot of docs prescribing these meds will keep patients on a maintenance dose once they reach goal weight.

I can’t speak to the use of rapamycin with a GLP-1. While I’m interested in starting rapa in the near future, I have not done so yet. My number one priority with regard to health and life extension has been weight loss, as before starting semaglutide I was starting to cross from the overweight into obese BMI levels.

I will note that it’s somewhat common to combine metformin with a GLP-1. One of the big telehealth providers specializing in GLP-1s (Calibrate) does or at least did consider this their standard practice, partially due to some insurance plans requiring that you try and fail metformin before they would cover a GLP-1 for diagnoses like insulin resistance, pre-diabetes, or PCOS. I did try it briefly (500mg/day) when trying to break a stall, and it had no noticeable effects for me.

Edited to add - I also re-read your OP and saw your question about using it to start or sustain a fast. I think it would be very promising for that use, as many patients find the appetite suppression to be profound.

There is evidence to support the idea that rapamycin can help you maintain a new set point in weight.

Are you taking rapamycin now?

Single rapamycin administration induces prolonged downward shift in defended body weight in rats

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See these:

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This makes perfect sense. Rapamycin mimics fasting. From water fasting alone I reset my setpoint by 35 pounds.

Very interesting! I am not taking rapamycin yet. Still doing my research on regimens and sourcing, but as I just turned 32, I think it’s time to start getting more serious about it (I know there’s a pinned thread that has wealth of info for younger people starting rapa)

Thanks!

Couple of things I saw you mention in those linked posts/threads that I wanted to mention.

1 - Regarding semaglutide dosing for weight loss, I’ve heard some doctors say that instead of just following the every 4 week dose escalation as outlined for diabetics, we should only be increasing the dose when we hit a weight loss plateau. My telehealth provider had me on .25 for 4 weeks, then I moved to .5 where I stayed for several months until I plateaued.

2 - Regarding fatigue with semaglutide, this is a very common side effect. Anecdotally, many semaglutide patients who have switched to tirzepatide (including me) have found it much better in that regard.

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Subjectively that certainly seems to be the case for me. I am now on my second round of rapamycin and have taken rapamycin for a total of about 11 months. After I started rapa my weight decreased from about ~185 lbs to 173 lbs. What is interesting to me is that my body seems to have stabilized at ~173 lbs regardless of diet and exercise. Before taking rapamycin I had to watch very carefully what I ate and how much I exercised. I have been doing TRF since before taking rapamycin. That helped, but I was having a hard time getting to my goal of 175 lbs.

On rapamycin, my body seems to want to be 173 lbs which is great because I don’t have to be quite as careful as to what I eat. This does remind me of when I was a teenager and didn’t gain weight no matter what I ate.

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Have you also practised extended fasts? Do you see a difference between fasting and rapa when it comes to setting a set point?

Given how hazy this literature on set points is, my thinking was that set point is a function of how long somebody has maintained some weight. That is set point reduces if one has maintained a low weight for a long time, and vice versa.

I only do extended fasts once or twice a year and that is when I am experiencing some subjectively perceived overload of supplements or if I have just not been feeling well for more than a few days.
I believe this to be true today:
" Hippocrates of Kos, the Greek physician and an outstanding figure in the history of medicine, told his patients: “To eat when you are sick, is to feed your illness”. The Greek philosophers Plato and his student Aristotle were also advocates of fasting."

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