Studies show that virtually everyone regains most if not all of the weight upon discontinuation. She should stay on the latest dose that allows her to stay at weight maintenance. So if she was continuing to lose weight at 5mg/week past her target goal, she might try reducing the frequency (eg every 8 days) or going back to 2.5mg/week. I would imagine that if she needed 5mg/week to continue losing weight, reducing the frequency is the right call. This is one of the issues with the large jumps in dosage with no simple way to do an in between dose with the auto-injectors. She could empty the injector into a syringe or other sterile container to draw up a custom dose.
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FWIW:
Taking into account that I am an ~84-year-old male:
I took tirzepatide for several weeks to lose that last bit of belly fat.
2.5 mg weekly was very effective. The two main things I experienced were appetite suppression and increased satiety from small meals.
It has been ~six weeks since I stopped. I still have very little appetite and the satiety factor remains the same. I am now struggling to eat enough to maintain my target BMI of 22.
So, for me, the most important thing that made tirzepatide work for me was its impact on satiety.
If I am hungry, it takes very little food to satisfy me.
The takeaway is this: Is your appetite still suppressed, or more importantly, do you eat less at meals?
If your experience is anything like mine, I would monitor my weight. If you are having trouble maintaining weight, start retaking tirzepatide.
I am unsure what dose you would take, but I would try 1 mg/week. I am surprised at how long the effects of tirzepatide last.
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Davin8r
#367
Any of the above doses/regimens could be true, and the experience between person a, b, and c is often completely different and requires self-experimentation. One thing is certain: she’ll regain the weight without at least some sort of maintenance regimen, unless she made permanent changes to energy intake habits that she can stick with despite the return of “food noise”.
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You shouldn’t go off the pharma protocol because of immunogenicity problem. It’s a real problem and even more if you’re using UGL peptides
The nice thing about GLP1-R’s is that you can easily measure the results. This allows rational dose modification to find the sweet spot. All one needs is a scale.
I lost on 3.5mg pretty consistently (1 lb a week), when I hit my goal wt I reduced the dose to 2.5, lost a bit more, but slowly (0.5lb a week) and then I went to a 2.0mg weekly dose, gained a few, that I was happy to welcome back 
and have maintained ideal wt.
My wife needed a bit more to lose (4.0mg) and her maintenance dose is 2.5mg.
The key is not to be in a hurry to make changes. Slow and measured is the way to go.
Weight management is a lifetime endeavor. Having failed at that for 40 years with “conventional” approaches, GLP1-R’s have given us an opportunity to be more healthy as we age.
With the many additional benefits, this peptide will be a staple until something “better” comes along.
I firmly believe it’s important to only do weekly doses so there is a peak and trough. People who do 2 or 4 “micro doses” (<1.0mg) a week are not doing themselves any favors. The 6 day half life then causes a consistent low level effect that seems to cause people to experience long term “stalls”
The peak and the trough are important.
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100% agree about the peak and trough. IME there seems to be a benefit to a larger deficit with the peak and then, at least for me, sometimes even a slight surplus in the trough. Historically I’ve had good success with calorie counting, however after 6-8 weeks I have lots of trouble with sleep, thyroid issues, testosterone dropping, etc. With tirzepatide I don’t seem to have these issues, despite being on average in a deficit for much much longer.
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Davin8r
#371
This appears to be a myth. For example, this study with exenatide showed less immunogenicity with more frequent dosing, and also decreased immunogenicity over time. More frequent dosing and time appears to create an immune tolerance effect:
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That’s great, but it’s only for exenatide. Every peptide is different. The FDA is really precocious about immunogenicity, every change of excipient, product concentration, injection frequencies have to pass new tests for approval
Davin8r
#374
There’s no reason to believe other GLP-1s are more immunogenic at higher dosing frequencies (if anything, the opposite given the study w/exenatide).
The drug companies use once weekly dosing because it is the least frequent regimen that still works and because the less frequent the dose, the better for sales. There’s no incentive for them to test 2x or 3x weekly doses (even if it were to work better and cause less side effects) because it would be a disaster for marketing.
If using a compounded version and self-dosing, lots of people do lower doses multiple times per week and have great results and less rebound hunger or other side effects. Others prefer the convenience of once weekly and tolerate the side effects well enough to do it that way.
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Yikes. This feels like fearmongering, and really hurts his credibility for me.
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KarlT
#376
I don’t think he is in agreement with the majority of physicians who would start GLP1’s with life style changes, rather than waiting 3-6 months.
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In a few years the primary treatment for obesity will become glp1s with the recommendation of eating more protein and fiber instead of telling people for decades to “just move more and eat less bro”.
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Agreed, in the long run, that only works for about 10% of the population.
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I am very intrigued by this new GLP1 agonist on trial, which only requires 1 shot a month.
Months after posting weight loss of 7.5% at 36 days for patients taking MET-097i, Metsera releases mid-stage results of just over 11% average body weight reduction at 12 weeks, with no plateau and a promising safety profile.
Just over three months after it commanded the industry’s attention with impressive Phase I data, Metsera is back with more promising findings for its investigational subcutaneous GLP-1 therapy MET-097i, which in a Phase IIa readout on Tuesday showed strong weight reduction and an encouraging tolerability profile.
After 12 weekly doses, patients on MET-097i lost 11.3% of their body weight on average, as compared with placebo. In the 1.2-mg dose group, individual responses reached as high as 20% in some cases. According to the biotech, all patients treated with MET-097i, regardless of dose, achieved “clinically meaningful and statistically significant weight loss” after 12 weeks.
Notably, Metsera had not yet detected a plateau effect at the time of the readout, indicating that MET-097i could elicit even greater weight-loss with longer dosing, the company said.
More on the trial here https://www.clinicaltrialsarena.com/news/metsera-announces-positive-results-in-newest-phase-iia-glp-1ra/
The randomised, double-blind, placebo-controlled trial enrolled five cohorts of 120 obese patients who are not type 2 diabetic. In all five cohorts, 20 patients received the active drug while four patients were given a placebo. Four of the five cohorts received 0.6mg, 0.8mg, 1.0mg, or 1.2mg, weekly, without titration, for 12 weeks. Patients in the fifth cohort were also given weekly doses but instead received escalated doses of 0.4mg for four weeks, then 0.8mg for a further four weeks, then 1.2mg for another four weeks.
John Buse, director of the University of North Carolina Diabetes Center, said: “Taken together, this data suggests that MET-097i has the potential to be a foundational therapy for people with obesity and overweight, by virtue of its effectiveness, compelling tolerability profile and flexible options for dosing, including titration-free weekly dosing and monthly dosing.”
Looks like weekly dosing to me?
The relevant quote in Metsera Touts ‘Powerful’ Weight Loss Results—Again - BioSpace
Additionally, pharmacological exposure to MET-097i accumulated over the study’s 12-week period, hitting a four-fold increase in concentration in patients who were dosed without titration. According to Metsera, this prolonged exposure to the drug is driven by its 15- to 16-day half-life and ultra-long-acting profile, which in turn could support monthly dosing.
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OK, weght loss in the obese. Fantastic news for the obese. I think? But I’m like the window shopper behind the glass - I see it, but how does this fit me? I am not obese. I do not need to lose weight. Will this drug prolong my life? Will it prolong the life of the obese person - I know they’ll lose weght, but prolonging life needs to be shown. Understandably we cannot know. Same as with rapamycin - we cannot know. Might it improve health in the obese? In the nonobese - will it improve my health?
Has this drug - or drugs in the same class - extended lifespan in mice the way rapamycin has, or canagliflozin (in males)?
If you want to lose weight for whatever reason, tune in. If you are looking for lifespan/healthspan, your heels are getting cool, and will stay cool for a long while yet. YMMV.
Since the trial was done with weekly dosing, they will need to do another trial with monthly dosing to be able to remove the word “could”
That will be a great advance for weight loss.
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Yes, of course, if you don’t need to lose weight, then this is probably not for you. That’s a given.
