I have searched the forum and seen others have been getting high resting heart rate from tirz but didn’t see anyone finding a solution. I’m currently using around 3 mg weekly and mg resting heart rate has gone from 60 to 80 is there anything I can do to help apart from stop the Tirzepatide? Is an increase like that a cause for concern with no other health issues? I know lots of people have a rhr of 80 and my fitness watch tells me my heart rate is average to good for my age group but I’m used to being a lot lower so it’s bothering me.
MESO-Rx
Anabolic Steroids
Anyone found a solution to high heart rate on Tirzepatide?
- Thread starter Hardtimes
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roofer22
Well-known Member
I should have been more specific. Lets not call it tolerance. But the ability to eat food and want to eat food comes back. When I first started sema I could barely eat on .25mg. Now I'm on a bulk taking 2.5mg eating fine. That's what I mean by tolerance. That doesn't come and go with weight fluctuation. At least not with me.GLP isn't an appetite suppressant. It's a naturally produced hormone that's central to the energy homeostasis (weight regulation) system.
Tolerance doesn't develop to insulin, or testosterone, requiring ever increasing doses.
All the evidence shows at a fixed dose, weight drops to a certain level, and stays there, with some minor variation, until the dose is titrated up, then weight drops more, and stays there until it's titrated up again.
Once treatment is stoped, in the overwhelming majority of cases, weight gradually returns.
If tolerance developed, then weight wouldn't stabilize for years at the same dose, but gradually return as tolerance builds. A "maintainance dose" wouldn't be possible, yet it clearly exists.
When people get bariatric surgery, weight loss and improved glucose control aren't because their stomachs are reduced in size, but because food moves into the intestines quickly, stretching them more than usual. Intestinal hypertrophy releases GLP-1, and this increased level of GLP has all the same effects as a shot of the exogenous GLP.
Basically, this is the *hard way* of compensating for a GLP hormone deficit vs injecting it.
The Role of GLP-1 in the Metabolic Success of Bariatric Surgery - PMC
Two of the most popular bariatric procedures, vertical sleeve gastrectomy (VSG) and Roux-en-Y gastric bypass (RYGB), are commonly considered metabolic surgeries because they are thought to affect metabolism in a weight loss–independent manner. In ...pmc.ncbi.nlm.nih.gov
If someone stays on the same dose of exogenous GLPs, and weight starts to return, that's a sign of immunogenicity, with antibodies developing to neutralize the drug. Immunogenicity didn't rise to a clinically significant level in the pharma trials of Sema and Tirz (it has with other pharma GLPs), but we're not dealing with carefully manufactured pharma products designed to minimize that reaction. It's entirely possible haphazard use of UGL versions are gradually making people immune to Sema and Tirz, reducing or completely eliminating their effectiveness.
Ghoul
Well-known Member
The other reason to avoid more frequent injections is that frequency of administration is a major factor in triggering stronger immunogenicity. Several small doses typically increase antibody levels much more than a single larger dose. In other words. the likelihood of immunogenicity going from "clinically insignificant", ie, not enough to have a measurable impact on the drug, to "clinically significant" leading to reduced effectiveness is higher.
"Typically, repeated administration is more immunogenic than a single dose, and immunogenicity increases with more frequent dosing and longer-term treatment "
Immunogenicity Challenges Associated with Subcutaneous Delivery of Therapeutic Proteins - PMC
The subcutaneous route of administration has provided convenient and non-inferior delivery of therapeutic proteins compared to intravenous infusion, but there is potential for enhanced immunogenicity toward subcutaneously administered proteins in a ...
pmc.ncbi.nlm.nih.gov
Ghoul
Well-known Member
If you've been going off and on, something I did years ago, the effectiveness when returning to Sema is often much lower. So much so I thought the batch for my second cycle was bunk. Then someone else with no prior use tried the same batch, and had as strong effect as I did the first time. A long time after that observation, others I spoke to had a similar experience, and more recently I've read anecdotal reports from clinicians who's observed the same in their patients. They needed much higher doses to get the same effect as before.
Obviously, it's still early days, research wise, with these compounds and even peptides in general, but re-exposure is a known risk factor with protein drugs. Meaning a break, vs continuous use, carries the risk of high immunogenicity when resuming treatment with the same peptide.
"Intermittent treatment or re-exposure after a long treatment free interval may be associated with an increase in immunogenicity. Previous exposure to similar proteins can lead to pre-sensitisation and cause an immune response."
I never suggested splitting up the dose, I said just increase the frequency, 15 mg every 5 days instead of 7The other reason to avoid more frequent injections is that frequency of administration is a major factor in triggering stronger immunogenicity. Several small doses typically increase antibody levels much more than a single larger dose. In other words. the likelihood of immunogenicity going from "clinically insignificant", ie, not enough to have a measurable impact on the drug, to "clinically significant" leading to reduced effectiveness is higher.
"Typically, repeated administration is more immunogenic than a single dose, and immunogenicity increases with more frequent dosing and longer-term treatment "
Immunogenicity Challenges Associated with Subcutaneous Delivery of Therapeutic Proteins - PMC
The subcutaneous route of administration has provided convenient and non-inferior delivery of therapeutic proteins compared to intravenous infusion, but there is potential for enhanced immunogenicity toward subcutaneously administered proteins in a ...
Ghoul
Well-known Member
That's still increased frequency. 15mg every 5 days is the equivalent of spitting up a 21mg once a week dose.
In other words, that's 7 injections every 35 days vs 5. Not nearly as significant as micro dosing of course. It's just that minimizing the risk of immunogenicity involves a bunch of factors, cumulatively adding up to a potential problem.
It's a really complex issue, and since no one is having antibody levels tested it's all feels based, so we're blind.
(HGH users can easily get tested for growth hormone antibodies, since that's a regular part of GH treatment most walk in test centers offer it).
Pharma prescribing guidelines for Sema and Tirz call for termination of treatment if the patient can't titrate up to a certain dose within 6 months. I thought that was weird, and wondered why staying at a low dose indefinitely could possibly be an issue.
It turns out that low levels of a protein drug tend to develop a stronger immune response than higher levels, so they want you to reach a minimum level for long term use.
If one has developed GH antibodies, is there anyway to reduce the level of antibodies and have the GH work again? Or one is just fucked for life?
Ghoul
Well-known Member
Likely not for life, but it has happened.
There's a chart below to illustrate. Bear in mind all peptides are subject to similar dynamics.
When a patient under HGH treatment isn't responding as expected, they're given an antibody test (RIA #). If it's high, they can either increase the dose (immunogenicity doesn't always go up with dose) to overcome the immune system neutralizing the drug, take a break and retry if and when the antibody levels go down, or switch brand of HGH in the hopes it won't trigger the same reactions
Here, the 3 patients with the strongest immunogenic reactions stopped growing completely. Two of them, 10 and 11, switched brands, showed no improvement, and treatment stopped. 15 took a 3 month break. antibody levels dropped, brand was switched, and treatment continued successfully. Another needed a 2 year break before treatment could continue.
Inhibition shows how much of the HGH was being neutralized, effectively lessening how well the HGH worked. So often HGH is still effective, even with high antibodies, but less than it would be normally.
With GLP users that develop this problem, it usually manifests as a loss of glucose control.
So it's not an "all or nothing" problem. Notice it can take a LONG time for immunogenicity to build. Often, antibodies build up quickly, then stabilize, in which case it's no problem (other than some degree of effectiveness may be reduced). But change brand, batch, or use a cheap vial that has some particulates in it, or one of the many immunogenic inducing factors, and it could rise again and become a serious issue.
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HB_22
Well-known Member
Just so people know there is no evidence at all to back up this claim other than just a few anecdotal reports from users who claim it to be weaker.
SubparMarioBro
New Member
Sorry to derail this but given evidence that GLP-1 is involved in addiction pathways (with widespread anecdotal reports of reduction in alcohol consumption) and given that bariatric surgery also works along a GLP-1 pathway, is there a link here between bariatric surgery’s effects on GLP-1 and the high incidence of alcoholism in bariatric surgery patients?
For example could the increased endogenous production in the intestines of a hormone with a 2-minute half life be leading to deficiencies elsewhere that are creating a vulnerability to substance use disorders (whereas the longer half lifes of semaglutide and co provide systemic effects that create the opposite effect)?
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