#244

Actually, I am glad to know that Tirzepatide gives a resting heart rate spike.

I ordered some Tirzepatide from a vendor I have never used before. It arrived undiluted, with no filler.
10mg in a 10cc bottle. It sure didn’t look like very much. Some of it looked like it was deposited on the side of the bottle. In any case, I reconstituted it with bacteriostatic water and took a 2.5mg dose around 11 a.m. Yes, indeed, it spiked my resting heart rate from 58 to 80 bpm.
So, maybe I got the real deal. No other peptide has raised my resting heart rate so far.
I will check my HRV, but my experience is that too many things affect it.
None of my healthcare providers give a shite about it.

This was the first day, and I will closely monitor my resting heart rate for the next few days.

FYI: My BMI is ~22, and I am in good shape. I am trying to eliminate a couple of pounds of lower abdominal fat.

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#245

Eli Lilly to test obesity medications as treatments for alcohol and drug addiction, CEO says

Company also wants to work toward over-the-counter access for weight loss drugs
“These medicines, we think and we’ve aimed to prove, can be useful for other things we don’t think about connected to weight. These are often called anti-hedonics, so they are reducing that desire cycle,” said Ricks, speaking at an event hosted by The Economic Club of Washington D.C. “Next year, you’ll see Lilly start large studies in alcohol abuse and nicotine use, even in drug abuse.”

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#246

Yes you did get the “real deal” :slight_smile:

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#247

My weight loss on Mounjaro is impressive and the health benefits for me indesputable. But the face ageing!?! :scream: Any hacks?

Am using NIRA laser daily. Tretenoin. Retinol and Ferulic Acid.

Hear its because adipose tissue loss and associated MSC.

#248

I’d avoid drastic weight loss over short period of time (if it’s too late for that, then I’d slow it down by lowering your dose so the problem doesn’t get worse). I’m currently alternating Fraxel laser 1 month with RF microneedling the next month along with daily adapalene + vitamin C/E/ferulic serum, but yeah, losing that subcutaneous fat (and muscle?) isn’t easy to fix without a “lift” of some sort. I avoid fillers because I don’t want to look like a person who’s obviously had fillers.

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#249

Just over three weeks of Retatrutide now. I dropped the dose a little so my appetite is back but it is still controlled, which is perfect. I’m trying to stay on 0.5mg 3x per week, so 1.5mg per week total.

Heart rate is still a little higher, but I feel good on it. I already had a full six pack before starting but I wanted to try it anyway because I felt like I was missing out on all the fun. I try to stay away from the scale but I did check and was down a few pounds.

One thing I do notice is that whenever I have a big cheat meal at a restaurant, I don’t feel as bloated from it and it’s all gone by morning. I’m thinking this is from the Reta. I have no plans of stopping.

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#250

Given that it is still experimental, what research or thinking did you use to decide your starting dose and subsequent protocol? Most of the sites I have looked at suggest a once-a-week dose. Did you experience any
For example:

"Retatrutide Dosing | Research Only
Researchers are advised to follow specific dosing protocols to ensure the safety and efficacy of retatrutide in weight loss studies. The dosing regimen starts with a low dose of 1 mg per week, which is gradually increased to minimize side effects. The recommended schedule is as follows:

Weeks 1-4: Start with 1 mg weekly
Weeks 5-8: Increase to 2 mg weekly
Weeks 9-12: Increase to 4 mg weekly
Weeks 13-16: Increase to 8 mg weekly
Week 17+: Reach the full dose of 12 mg weekly
It’s essential that researchers do not exceed the maximum recommended dosage of 12 mg per week. Retatrutide is designed for once-weekly subcutaneous administration, and due to its extended half-life, it can be injected at any time of day, with or without food [6, 7]."

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#251

Lots of people prefer multiple smaller doses per week to smooth out the peaks and valleys of the medication regimen. For instance with semaglutide and tirzepatide, many report a resurgence of hunger on day 5/6 on a once weekly dose regimen, but no such resurgence if they split the dose in half or in thirds and spread the dose out throughout the week.

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#252

My experience is that once weekly remains the gold standard.

I’m not going to say how many people I know doing this weekly but it’s more than 2. A few even strayed from the weekly protocol and all came back home. Yes the first month or so can be more “difficult” to adapt to but that is also part of the process of acclimating to GLP1-R’s. Once people are past that, the lights turn on and the energy level and happiness that comes with the new body image cements the process,

A bit of “food noise” near the end of a week should be tolerable… for an adult :slight_smile:

Having a high peak and a declining level of the GLP1-R of choice is not bad thing, in fact it’s the way it was designed to work and all the weight loss trials show this dosing protocol is very effective.

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#253

I was hoping to get the benefits and reduce potential side effects. There are people on TRT who do this as well. It probably wouldn’t make much of a difference either way, I don’t think. The only side effect I’ve had is increased resting heart rate.

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#254

My plan as well, love Reta.

But some people find Tz to be their cup of tea.

If a person is really bothered by “food noise” they will probably prefer Tz over Rt early on.

I too don’t mind being a bit hungry and eating more than I should once in a while, it feels more human to me. And the Reta looks after my indiscretions the next day or two.

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#255

The weekly doses are designed around one thing – minimum injection frequency to sell the drug. Less frequent injections are a huge incentive for needle-averse prospective patients. Maritide will be the first once-monthly GLP/GIP injection, and that’s its biggest selling point.

Even if the drug is more effective and better tolerated with 3 smaller injections per week, no pharmaceutical company is going to try and market this if they can get away with once per week because the overwhelming majority of patients simply aren’t motivated enough to start (or stick with) a 3x weekly vs 1x weekly regimen.

Those of us in the biohacking community, however, are perfectly willing to do what it takes for optimal efficacy and better tolerability. :smiley: Just check the GLP forums – many, many, many people break up the dose to reduce side effects while maintaining efficacy.

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#256

I frequent a few of those sites for amusement :slight_smile:

Interestingly “many, many, many” is not 10’s of millions, with over 35 million in the US alone who have used GLP1’s in the prescribed way “many” doesn’t even come close and that is not counting another 100 million or so in the rest of the world.

Most of those sites are setup to support a vendor or 2. If you see specific discount codes, limited vendors, what you are seeing is money. I’m not against that, but I do understand those groups were not setup for honest discourse on difficult scientific subjects. They were set up to make someone money. Either the Admins with side hustle “consulting”, product promotion, or vendor promotion that in turn is compensated through affiliate links.

I’m way more familiar with that business model than most as I’ve used it in the past and will use it in the future.

I love it when people decry “big pharma” and then use their products though :slight_smile:

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#257

Just to be clear, I’m not saying it’s a bad idea to use the GLPs once weekly. After all, as long as it’s working and side effects are tolerable, the fewer the injections the better. People using the branded versions don’t really have a choice with the fixed dosing pens and doctor’s instructions. I’m also not decrying big pharma for making money or using the best dosing schedule to promote sales – just stating that’s how it is when it comes to the studies using the least frequent dosing regimens – it’s to promote maximum sales uptake of the drug, not because of inherently enhanced efficacy vs more frequent, lower doses. It’s also to keep things as simple as possible for the average patient who might might very well screw up the dosing regimen the more frequent and/or complicated it is.

I don’t know of any published data comparing efficacy and side effects of (for instance) 5mg tirzepatide Q week vs 2.5mg twice weekly, and I don’t see anyone paying for such a study when it would only potentially complicate things for Eli Lilly.

#258

I would make a significant modification on this as this is starting too low and then not putting parameters for dose adjustment.

For Retatrutide, I start folks on 2 mg q7 days subcutaneously.
Wt loss the first 4 weeks is not predictive, and if losing >1 lb per week don’t get excited, but beyond 1 month, need to stick with the 0.5-1 lb wt loss/week. Closer to 0.5 is ideal. Slow and steady wins the race, but also avoids the situation of muscle preferentially being lost.

I have people adjust dose from 2 mg to 3 mg and only go up 1 mg/dose/month, but most folks are going to get to the goal at 4 mg with these parameters, then once at ideal body weight (or better yet looking good by DEXA) then adjust dose down to what has you sustain this body weight.

Going off of these is not good, as weight gain happens rapidly, and is almost all fat, and as such, your body composition will often times be worse than when you started.

Weight lifting is critical with being on GLP and actively losing weight.

Apart from $$ there is no reason to come off these, they are drugs that have substantial longevity benefits.

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#259

That’s probably true. The first GLP1RAs were twice daily (exenatide as Byetta in 2005) and once daily (liraglutide 2010 and lixisenatide 2016). The class took off with once-weekly injections (exenatide long-acting as Bydureon in 2012 and albiglutide and dulaglutide in 2014 until King semaglutide in 2017).

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#260

These peptides are evolving in the R&D dept’s of quite a few drug companies, almost all seeking to make it easier and longer lasting. Easier through an oral solution and longer acting, up to a month per '“dose”. Even Eli Lilly is going down this path, not sure they are concerned about “complicating things” not to mention Novo Nordisk…

Free market forces at work, adapt or get left in the dust :slight_smile:

Versanis’ lead asset is bimagrumab, a monoclonal antibody that binds activin type II A and B receptors to block activin and myostatin signaling. Bimagrumab is currently being assessed in the BELIEVE Phase 2b study alone and in combination with semaglutide in adults who are overweight or obese.

https://investor.lilly.com/news-releases/news-release-details/lilly-acquire-versanis-improve-patient-outcomes-cardiometabolic

The acquisition of Inversago includes the company’s lead development asset INV-202, an oral CB1 inverse agonist. INV-202 is designed to preferentially block the receptor protein CB1 – which plays an important role in metabolism and appetite regulation – in peripheral tissues such as adipose tissues, the gastro-intestinal tract, the kidneys, liver, pancreas, muscles and lungs.

INV-202 demonstrated weight loss potential in a phase 1b trial and is currently in a phase 2 trial for diabetic kidney disease (DKD). Additional pipeline assets are also being developed for metabolic and fibrotic disorders. Novo Nordisk intends to investigate the potential of INV-202 for obesity and obesity-related complications.

This is a huge market (no pun intended) with many players looking to get fat off the fat…

#261

My bet is that the suicide risk is directly related to the weight loss efficacy. Being in a caloric deficit over a long period of time is a big hit to mood, and a deeper deficit should be expected to lead to greater mood disturbance.

#262

Some studies have also reported cases of anhedonia associated with GLP-1 RA use. And albeit not the best source, Reddit has quite a lot of reports of people that claim to experience this - not just when it comes to food (or alcohol) consumption, but also reduced interest in daily aspects of life or reduced sexual desire, etc.

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#263

I mean complicating things if they paid for a study that found 3x weekly tirzepatide worked better and was more tolerable than 1x weekly. They don’t want a more complicated dosing regimen (once weekly or once monthly or less for injections, once daily for a pill). For a new 3x weekly dose, Eli Lilly would have to manufacturer a bunch of new fixed dosage pens and there would be all kinds of confusion and mistakes from the prescriber to the pharmacy to the patients. It would be a dumpster fire.

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