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

Something I wanted to report here as I use tirzepatide is a potential for harmful effects. I use it from a multiuse vial. As a peptide sits around reconstituted the peptide degrades in strength.

I started at 2.5mg, and moved up to 5mg. I think by the time I had moved to 5mg the peptide strength had degraded to a fairly significant degree. When I got a new vial of tirzepatide and did my first 5mg dose from this I had a very dramatic reaction as it was freshly reconstituted. I had intense nausea and stomach gas.

For this reason it is advisable to get smaller amounts of mg in a vial and get more vials, and reconstitute them as you go (or have a compounding pharmacy do this for you.) This prevents anything happening like that.

It’s funny I just started rapamycin this week and I almost blamed rapamycin for all of these effects I was having, and it only just clicked last night as I was sitting up in bed with this nausea that this seemed more like a GLP1 reaction. I’m glad that is the case! While the side effects suck, they will pass and I will adjust to this dose of tirz. At least I’m not intolerant to rapamycin :sweat_smile:

I always keep mine refrigerated for that reason.

Mine was refrigerated. It just took a while to use it all up. Now that I’ve increased dosage it should go faster and not be as dramatic. I might look to lower the dose slightly every time I change vial to avoid this sudden unexpected jump however, I’ve had a rough couple of days haha.

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How old was the vial by the time you increased to the 5mg dose?

Correct, for most peptides one should only reconstitute a 30 day supply. This is the reason I do custom vials based on 30 day requirements.

One exception to this is TA-1 you must use this up in 7 days from reconstitution.

So it’s important to be aware of these time frames, your desired dose and how long a vial will last.

For example if you are on a 2mg dose of Tz you want a 8mg vial, if a 4.5mg dose you want a 18mg vial, etc.

For something like BPC 157 where you may be taking 500mcg per day you want a 15mg vial or 2x 10mg would work if you only reconstitute 1 at a time as you use them.

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I’m planning on titrating dose so I got larger vials. I’m going to lower the number of units on the syringe I use every time I start a new vial. What do you think of this idea?

The way to do this so you have good product over time is;

  1. vial size / by dose = total doses
  2. then dose frequency
    once a month?, 2, 5, 7 days a week x 4?
    Does that number then use up the vial in 30 days/?

For example, if you have a 20mg vial and use a dose of 3mg you would have 6 doses at 3mg and 1 at 2mg. This is 7 doses if you take 1 per week this is not a good vial size for that dose as it’s 3 weeks past the 1 month cut off.

When you say ā€œtitratingā€ that is a bit ambiguous, as I don’t know;

  1. starting dose
  2. up or down?

Also units is not dose, its a volume of liquid and the dose depends on the dilution ratio. This is one of the common issues with folks injecting, they often tell me ā€œI take x unitsā€ and that doesn’t tell me anything about the dose. What one would need to know is mg/unit or vial mg and mL of bac water used to reconstitute

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I know units aren’t the dose, but if the peptide strength degrades over time then the calculated mg to unit ratio is also not the dose.

I’m titrating the dose of tirz up by 2.5mg every 5th week as per the standard practice with it. The problem is when I do this the peptide degrades so that when I get the new vial that new higher dose is much stronger than I’m used to, so I may just use less units on the syringe compared to how I was calculating the dose on the previous vial to compensate for that and then slowly increase over the next few doses to adjust.

The stronger anti-inflammatory effects that I am seeking from it come from these higher doses I believe. It is shown in studies to benefit asthma and sleep apnea so I’m hopeful it helps me with these issues.

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And do you know the % of degradation over time? I don’t.

The 30 days is what is recommended and over that time period there is no degradation from what is indicated by ā€œbig pharmaā€. When it does start to be less potent, I don’t know if its linear or otherwise. So any titration to compensate would be a shot in the dark.

That’s why it’s best to stay in the ā€œstabile zoneā€ of 30 days for most peptides.

Generally speaking, if I went past the 30 days, personally I’d still go by the calculated mg dose as I’d know I would not go over. That may not be the most financially smart way to do it but it’s the safest way.

Although the worst case would depend on the peptide. Some it would not matter if one went 50 to 100% over, some it might. GLP1’s are probably in the ā€œit mightā€ category for me. A small bump up would probably not matter at all. So if you are doing a small compensation, you are probably not going to have any issues and if you did, you can fix it with the next dose :slight_smile:

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Luckily once I get to higher doses I will be in that 30 day window and it won’t be an issue.

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Reconstituted tirzepatide shouldn’t degrade that much over 30 days , assuming purity is over 99% to begin with. In fact, there have been several degradation tests where reconstituted tirzepatide was frozen 2 to 4 times, and significant degradation didn’t take place until the solution was frozen the 4th time.

Anecdotally, I routinely go over 30 days with my reconstituted vials, and don’t notice a drop in efficacy. This is on tested product with over 99% purity.

This doesn’t generalize to all peptides, but this peptide in particular has shown itself to be pretty sturdy.

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I had it for longer than 30 days. First vial I had for about 2 months. Depending on what dose I go up to I can get a vial to last 6 weeks, or 4 weeks, or even less.

I may stick with the 4 week dose just for simplicity. I don’t necessarily need to go to a higher dose.

I could trial splitting the weekly dose in half and taking it 2x a week. Has anyone tried this?

Most people that I see doing split dosing do it to lessen side effects. They still lose weight, but splitting probably affects efficacy of the medicine, since in trials they don’t do split dosing. But that is just my guess.

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I would not do that due to the long half life of 6 days.

From what I’ve seen, people who do that do often have 1 side effect. Stalling. I see the ā€œstallā€ thing on many social media groups and many of those people are doing multiple shots per week ā€œto minimizeā€ side effects. If they did a low weekly dose for a few more months there would be zero side effects. Low and slow is the key for a life time program like this.

This peptide is designed for a once weekly dose to provide a high peak and a low trough before the next dose. Not having the low trough may be an issue and possibly cause desensitization.

Rigorous clinical trials have been run on Sema, Tirz and Reta with 1 dose per week and with great success. I don’t see the need to reinvent the wheel on this one.

Also they provide a dose dependent effect. I’ve also seen people asking why they are not losing any more when they have been on a sub-clinical dose of 2mg for 6 months. I see a lot of guessing, gnashing of teeth and additions of this and that to ā€œbreakā€ the stall. All that needs to be done is follow the clinical evidence, up the dose. I got banned on one chat forum for saying this. That would have had a negative effect on the influencers consulting fees and supplement sales LoL!

The clinical dose range of Tz is 2.5mg to 15mg per week. Keeping in mind the primary purpose of GLP1-RA’s is glucose control for T2D, an effective weight management dose is not typically that high for non-T2D people.

In my experience I’ve not had anyone I deal with need to go over 10mg per week and those are a few women in various stages of menopause. Most people do fine in the 2.5 to 6mg range with no side effects after full acclimation.

Full acclimation is not an overnight thing, it’s not even a 30 day thing so I encourage people to not worry about the weight loss for the first 2 to 3 months.

Been on 1 weekly dose of Tz and/or Reta for 21 months now, have never felt better :slight_smile:

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Personally I don’t typically do this. We shoot for a weight loss/management goal.

  1. are you losing 1lb per week? if yes you are on a good dose, don’t change it
  2. if not, then up the dose proportionally,
    if you are at 2.5mg go to 3.5
    If you are at 3.5mg go to 5mg

There is no rush :slight_smile:

If someone is losing more than 2 lb’s per week the dose is probably too high but again patience, wait a couple weeks to see if it stays at 2 or drops back down to 1.

From what I’ve seen, big changes cause discomfort. I encourage people to think of this as a life time intervention and that requires some patience with self and the product.

I was overweight for 50 years, expecting to be at a healthy weight in a few months was one how I got there.

Once I experienced the rock solid consistency of 1lb a week a weight was lifted (no pun intended) :slight_smile:

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I’m not obese. I’m using it for anti-inflammatory effects.

Also for sleep apnea. I know people think the primary mechanism of tirzepatide helping with sleep apnea is weight loss but I’ve seen evidence that it helps before weight loss is achieved meaning it has some other mechanism that benefits. I don’t remember what study that was.

I am trying to lose visceral fat though.

It’s possible higher doses are needed to achieve these effects.

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OK, you will still want to watch your weight then as you go up in dose. If you start losing weight you don’t want to lose, your dose may need to be lowered.

The scale is the best way to monitor this and help titrate up or down to the ideal dose for your goals.

I recommend to my clients that they weight themselves every day, same time, first thing in the morning for at least the first 2 to 3 months. It’s the easiest way to manage the dose.

Funnily enough my scale broke recently. I am certain I’ve lost fat, but maintained muscle.

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Steve_Combi is correct (at least for me). 2mg of tirzep evry 2 days was not very effective (poor wt loss and very little control of hunger) -same or more side effects, whereas 6mg every 7 days was extremly effective. HRV took about 4 months to return to normal and now I have zero side effects from Tirzep. (16 months user)

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Actually Eli Lilly states the shelf life of unopened refrigerated Mounjaro is 24 months. I thought Janoshik did a study on this, but I can’t find it right now.

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