Tirzepatide - a better semaglutide? (GIP + GLP1 agonism). Also LY3437943

tirzepatide

https://www.nejm.org/doi/full/10.1056/NEJMoa2107519

GIP agonism might be better for the bones too (compared to Miglitol - a better acarbose? Increases UCP1, decreases gastric inhibitory peptide (GIP) + decreases body weight )

Can also increase osteoblast activity - Tirzepatide's Unique Mechanism of Action - GIP/GLP-1 Dual Agonist - YouTube

It IS possible to get via india-mart

THEN THERE IS a BETTER one (LY3437943) -

God I find out about things so late… I only learn of semaglutide within 1 year of learning of ALL the newer stuff (similarly with canagliflozin)

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Friend I know just tried it and says it’s way better than semaglutide

Better in what ways? Please provide more detail…

20% weight loss versus 15%

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Can 1mg tirzepatide work as well as 1mg semaglutide? (tirzepatide uses higher doses but is more effective, so uh, maybe half or 1/4 the dose of tirzepatide for similar effect?)

Tirzepatide is also way more expensive per mg.

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I just injected 1mg 2 days ago, and another 1mg yesterday. did not have appetite loss yesterday.
the “effective starting dose” is 2.5mg titrated up to 5 mg per week. Also, half-life of 5 rather than 7 days.

it is MUCH more expensive than semaglutide. Since SLG works well enough for me, I don’t feel the extra cost is worth it (right now)

What degree of CR do you aim for? Are people in the CRON world using these meds to help with CR?

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I am on my 4th month of tirzepatide. Most amazing medication I have ever taken. From day 1 it gave me total control to eat only healthy foods. I do time restricted eating, low calorie, and can easily fast for a day or more. Several health markers improved and I lost 40 lbs in 9 weeks.
Titrating up the dose and the day after an injection can be a little rough sometimes. I never had any gastrointestinal issues that some do, but I have had occasional general malaise, feeling cold, heart burn, and insomnia.

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The vast majority of people I know of (myself included) who have tried tirzepatide and semaglutide greatly preferred tirzepatide because of the side effects profile. It’s also often immediately effective without the weeks/months of slow dose titration that many need on sema because of the sides.

Retatrutide is even better in that regard. You can feel very much normal, even energetic on retatrutide. Tirzepatide… not as much.

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I agree, from the 1st day I could go without eating. After being on it for a while, my energy level is pretty good. It has been life changing for me.

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You don’t need slow dose titration on semaglutide. I know because I didn’t need it the first time I did it.

I wish finances were not a concern, but they are a bit of one. 5mg of tirzepatide (which is 1-2 doses) is $70. 5mg of $70 semaglutide is 10-20 doses…

[if you source properly…]

(and semaglutide lasts longer)

Semaglutide is like $7-8/dose. Tirzepatide is $35-70 per dose… [though if it made you eat proportionately less food, then even tirzepatide could be worth it]. Semaglutide side effects have never been too much for me.

I tried half the active dose of tirzepatide [~1mg] yesterday and it isn’t decreasing my appetite…

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Not generally true, so you could be an exception. What was your starting dose though? I’ve been on half a dozen forums with people on these drugs for over a year, and most need to start very low and titrate up slowly (as officially recommended) or they get pretty sick. I was already used to tirzepatide when I had to try semaglutide due to a shortage, and sema at a supposedly equivalent dose was a bit rough.

Re 1mg, I started tirzepatide at 2.5mg. I wouldn’t expect you to have any appetite suppression at 1mg, though I know of one reported case at 1.25. Even at 2.5 some people don’t “feel” anything for a few days or even a few doses or until a higher dose. Some get lucky and can stay at 2.5 for quite a while, but most need to steadily increase as time goes on.

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Great example of n of 1.
Essentially every patient I’ve seen with a complication of a GLP1 has resulted from too high an initial dose or too large an increase in dose either accidentally or intentionally.

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I prescribe these quite a bit, so have a lot of experience - and like @KarlT get to see the issues when things go bad, in the ER.

Given that semaglutide is really just a GLP-1 agent, and tirzepatide is stronger on GIP and weak on GLP-1, we see some patients do better on one than the other in regard to tolerability. In regard to efficacy, I find ~1 mg of semaglutide to get the same efficacy as ~2.5-3.75 mg of tirzepatide.

Overall maximal wt loss will occur on tirzepatide - but is dose dependent and also highly dependent on the advice and plan the patient has been given by hopefully a highly skilled physician who doesn’t just Rx the med (which seems the norm these days) and not provide all the other scaffolding needed.

I get semaglutide in the U.S. for 12.5 mg for ~ $260 and tirzepatide 34 mg for ~ $300 - depending on dose there isn’t a massive difference in cost per week if looking at 1 mg vs. 2.5 mg. However, I know others are getting it off shore - but this is a problem as these drugs degenerate quickly if not refrigerated -and who knows what happens in transport???

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“this is a problem as these drugs degenerate quickly if not refrigerated -and who knows what happens in transport???”

Do they degenerate quickly if just left as lysophilized powder at room temperature though? They can supposedly last several months if just powder. it’s adding teh water that maeks them easily degraded at room temp

[i left them at room temperature as lysophilized powder, this might have been a mistake]

" Essentially every patient I’ve seen with a complication of a GLP1 has resulted from too high an initial dose or too large an increase in dose either accidentally or intentionally."

These are still a minority

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Yes - the powders are fine in the fridge - not freezer generally - but look at the container - most of the time storage 50-75 degrees F. The issue is often rapid degeneration at really high temperatures - and in transit - really easy, especially in summer to be at 120-140F.
My shipping to patients is refrigerated.

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This discussion is timely, because the peptide community, for lack of a better term, has actually been performing a lengthy series of tests looking at degradation of tirzepatide under different conditions. All of the potential issues above have been concerns and the subject of much speculation and debate since the GLP party started.

The test results are currently held by those who helped pay for the testing, but they will eventually be publicly released. All I can say at this time is that I think all concerned would find the results surprisingly reassuring and would be more inclined to consider buying from overseas. I continue to store vials in the freezer…

Enough hints. :slightly_smiling_face: I hope to be able to share data at a later date.

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are the powders fine at room temperature for several months? [as long as one doesn’t dissolve them]

[that’s what i did with my tirzepatide, but I left them at like 60F for several months

i’m on my 3rd straight day with a full appetite and ate 3 cans of black beans + quizno’s salad + strawberries + nuts, it’s not great for me [though i can survive it because I went through some semaglutide weight loss]

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Just injected 4/10 of 5mg

I think the increased self control/decreased noise might be better, but I’ll need more time to assess

I injected an air bubble first, it doesn’t hurt much, though it created a cavity/bump

Larger injection sizes are more likely to cause injection area side effects, maybe this is minimal with experience

TIPS ARE REALLY FRAGILE , mine almost broke

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What is your BMI if I may ask, what are you targeting?