Opinion/anecdote: Don't be afraid of increasing your dose

[gulangaloid]

It seems like overwhelmingly, no matter where I see GLPRA discussion, there is a great amount of advice to keep your dose as low as humanly possible and to start and stay at doses far below even the normal STARTING clinical trial values. I'm not sure how much of this is already lean and healthy bodybuilder types, but for people that the drug was actually designed for (overweight/obese/T2D) I would personally suggest (I am not a doctor) that you ignore most of that unless you find yourself being a super responder.

While the sentiment that if you are achieving healthy results that you are happy with you don't necessarily need to increase the dose on a rigid schedule I certainly agree with, I don't think being overly cautious about increasing dose (assuming side effects are tolerated) is going to help people trying to deal with obesity (the people the drug was meant for) provided that the doses and the titration are in line with the clinical trials. If you are obese and just happen to be a super responder losing all they weight they can dream of, I really am thrilled for you, and I don't want to make you change what you're doing. However, this advice is not for you.

To be clear, I don't mind that bodybuilders are taking drugs for obese people, people can do whatever they want with their bodies. Thin people can take whatever they want, but the needs of a thin, healthy person and an obese person are extremely different, and I strongly believe that the latter following the dosing examples/advice of the former can impede progress and be harmful. I would also strongly suggest not worrying about getting into stacking or changing your GLPRA before you have been on the maximum dose of your GLPRA of choice for at least a month or two without meaningful results.

This sort of stems from my anecdotal situation, where I saw little to no results from the early doses of reta. I was staying the same weight, occasionally gaining or losing a pound. I was even worried I might have gotten a bum shipment. However, when I started the maximum dose, I fairly quickly started to see strong results with manageable side effects. This has also been consistent across multiple shipments from multiple suppliers, so the quality or fill of the product does not appear to have been the issue.

 

[Labcat]

It seems like overwhelmingly, no matter where I see GLPRA discussion, there is a great amount of advice to keep your dose as low as humanly possible and to start and stay at doses far below even the normal STARTING clinical trial values. I'm not sure how much of this is already lean and healthy bodybuilder types, but for people that the drug was actually designed for (overweight/obese/T2D) I would personally suggest (I am not a doctor) that you ignore most of that unless you find yourself being a super responder.

While the sentiment that if you are achieving healthy results that you are happy with you don't necessarily need to increase the dose on a rigid schedule I certainly agree with, I don't think being overly cautious about increasing dose (assuming side effects are tolerated) is going to help people trying to deal with obesity (the people the drug was meant for) provided that the doses and the titration are in line with the clinical trials. If you are obese and just happen to be a super responder losing all they weight they can dream of, I really am thrilled for you, and I don't want to make you change what you're doing. However, this advice is not for you.

To be clear, I don't mind that bodybuilders are taking drugs for obese people, people can do whatever they want with their bodies. Thin people can take whatever they want, but the needs of a thin, healthy person and an obese person are extremely different, and I strongly believe that the latter following the dosing examples/advice of the former can impede progress and be harmful. I would also strongly suggest not worrying about getting into stacking or changing your GLPRA before you have been on the maximum dose of your GLPRA of choice for at least a month or two without meaningful results.

This sort of stems from my anecdotal situation, where I saw little to no results from the early doses of reta. I was staying the same weight, occasionally gaining or losing a pound. I was even worried I might have gotten a bum shipment. However, when I started the maximum dose, I fairly quickly started to see strong results with manageable side effects. This has also been consistent across multiple shipments from multiple suppliers, so the quality or fill of the product does not appear to have been the issue.

Very quality anecdotal data. I’ve been consdering about the things that couldl cause a vial to seem weak, this is a great reminder that sometimes a person just responds later and if you don’t with different “brands” you wouldn’t really know.

 

[Foggy-Hollow]

This sort of stems from my anecdotal situation, where I saw little to no results from the early doses of reta. I was staying the same weight, occasionally gaining or losing a pound. I was even worried I might have gotten a bum shipment. However, when I started the maximum dose, I fairly quickly started to see strong results with manageable side effects. This has also been consistent across multiple shipments from multiple suppliers, so the quality or fill of the product does not appear to have been the issue.

Your personal response is exactly that: personal. If someone is getting good response (1-2 pounds per week) on half the amount you are taking, there’s no data-driven reason to up the dose.

The advice to start low and slow is coupled with watching how the body is reacting. It’s not standalone advice.

 

[yrrdead]

I don't get posts encouraging people to send it regarding doses. Grey market, unknown fill, unknown reaction. Caution is warranted imo. Also this is a marathon not a sprint. Hard to have a longer term outlook and no instant gratification but that gets easier with age (at least for me).

It is easy to take another dose after 3 days. Or bump it next week. Quite a bit harder to uninject 12mg.

My anecdote - obese 220@5'8"M. Currently @ 185. Started Oct 1st @ .5mg e3d. But what is that worth?? Nothing.

If anyone asks me I link them the trials showing many different titration schedules. Maybe show them a shotsy chart or glp1plotter to give them an idea of buildup. But to be fair most people don't want to read or actually research. They want simple numbers and an easy schedule.

 

[Labcat]

Your personal response is exactly that: personal. If someone is getting good response (1-2 pounds per week) on half the amount you are taking, there’s no data-driven reason to up the dose.

The advice to start low and slow is coupled with watching how the body is reacting. It’s not standalone advice.

Not at allsuggesting anything happens to everyone. But it’s still very helpful to see what variations people have when they systematically vary something (like compounding source). Because there is s paucity of research, and many RS’s who communicate their experience, a kind of lore around glps has developed that include things like how a response is wildly and intensely individual, and while some say tirz is tirz (which is what the fda believes), many say that something about compounds are different. ) (I wonder if some of that is from inaccuracies in formulating, sourcing, or storage.) In this particular case it was just super interesting to see a systematic report that compounders did not differ for them, and the increased tolerance stayed with this RS, even though official conclusions from EL’s papers say that tolerance does not develop.

 

[gulangaloid]

Your personal response is exactly that: personal. If someone is getting good response (1-2 pounds per week) on half the amount you are taking, there’s no data-driven reason to up the dose.

The advice to start low and slow is coupled with watching how the body is reacting. It’s not standalone advice.

Did you not read what I wrote?

 

[desinr-gal]

Did you not read what I wrote?

You acknowledged the point, but then negated it's value. You are wrong. In the latest studies there is a percentage of people who lost just as much weight while on placebo. The previous trials showed a percentage of people lost the highest % of weight on minor doses. These % were small in comparison, but statistically significant.
Meanwhile there are a not insignificant number of users who end up in the hospital, because they dosed too high and had severe reactions.
I raised my dose of reta by 1 unit yesterday and my BPM jumped to over 100 for several hours.

Every body reacts differently. Since thousands of new users have joined this forum to learn, it is
irresponsible to tell them to up their doses willy nilly.

 

[bogardbilla]

If anyone asks me I link them the trials showing many different titration schedules.

Would you be so kind and post links to these different titration schedules? I'd love to learn more, thank you.

 

[dndgeek]

You acknowledged the point, but then negated it's value. You are wrong. In the latest studies there is a percentage of people who lost just as much weight while on placebo. The previous trials showed a percentage of people lost the highest % of weight on minor doses. These % were small in comparison, but statistically significant.
Meanwhile there are a not insignificant number of users who end up in the hospital, because they dosed too high and had severe reactions.
I raised my dose of reta by 1 unit yesterday and my BPM jumped to over 100 for several hours.

Every body reacts differently. Since thousands of new users have joined this forum to learn, it is
irresponsible to tell them to up their doses willy nilly.

Seriously one unit did that to you?

 

[yrrdead]

Would you be so kind and post links to these different titration schedules? I'd love to learn more, thank you.

Here's kind of a meta analysis that was done with tables and links to the original studies. Its a bit much but dig in;

Efficacy and safety of retatrutide, a novel GLP-1, GIP, and glucagon receptor agonist for obesity treatment: a systematic review and meta-analysis of randomized controlled trials - PMC

Retatrutide is a novel triple agonist targeting the receptors of glucagon-like peptide 1 (GLP-1), gastric inhibitory polypeptide (GIP), and glucagon. We sought to assess the efficacy and safety of retatrutide in obese patients with or without ...

pmc.ncbi.nlm.nih.gov

 

[dndgeek]

Here's kind of a meta analysis that was done with tables and links to the original studies. Its a bit much but dig in;

Efficacy and safety of retatrutide, a novel GLP-1, GIP, and glucagon receptor agonist for obesity treatment: a systematic review and meta-analysis of randomized controlled trials - PMC

Retatrutide is a novel triple agonist targeting the receptors of glucagon-like peptide 1 (GLP-1), gastric inhibitory polypeptide (GIP), and glucagon. We sought to assess the efficacy and safety of retatrutide in obese patients with or without ...

pmc.ncbi.nlm.nih.gov

Gold, thank you!

 

[gulangaloid]

You acknowledged the point, but then negated it's value. You are wrong. In the latest studies there is a percentage of people who lost just as much weight while on placebo. The previous trials showed a percentage of people lost the highest % of weight on minor doses. These % were small in comparison, but statistically significant.
Meanwhile there are a not insignificant number of users who end up in the hospital, because they dosed too high and had severe reactions.
I raised my dose of reta by 1 unit yesterday and my BPM jumped to over 100 for several hours.

Every body reacts differently. Since thousands of new users have joined this forum to learn, it is
irresponsible to tell them to up their doses willy nilly.

so you didn't read what i wrote, got it

 

[bogardbilla]

Here's kind of a meta analysis that was done with tables and links to the original studies. Its a bit much but dig in;

Efficacy and safety of retatrutide, a novel GLP-1, GIP, and glucagon receptor agonist for obesity treatment: a systematic review and meta-analysis of randomized controlled trials - PMC

Retatrutide is a novel triple agonist targeting the receptors of glucagon-like peptide 1 (GLP-1), gastric inhibitory polypeptide (GIP), and glucagon. We sought to assess the efficacy and safety of retatrutide in obese patients with or without ...

pmc.ncbi.nlm.nih.gov

Thank you!

 

[Calm Logic]

Here's kind of a meta analysis that was done with tables and links to the original studies. Its a bit much but dig in;

Efficacy and safety of retatrutide, a novel GLP-1, GIP, and glucagon receptor agonist for obesity treatment: a systematic review and meta-analysis of randomized controlled trials - PMC

Retatrutide is a novel triple agonist targeting the receptors of glucagon-like peptide 1 (GLP-1), gastric inhibitory polypeptide (GIP), and glucagon. We sought to assess the efficacy and safety of retatrutide in obese patients with or without ...

pmc.ncbi.nlm.nih.gov

Damn, a couple of them had 4 mg to start. Crazy.

 

[Waclive]

In all my years of experimenting with new things, what's always served me well is starting low and adding more as I see fit.

I feel like encouraging people to go full bore will deter them from using the tool as intended and having good results versus their first experience with a GLP-1, since they didn't start with a doctor, being a bad experience and are robbed of the joy of seeing the pounds melt away.

 

[desinr-gal]

Seriously one unit did that to you?

yes There is no other explanation. I had been pinning 1.2 of reta, and yesterday I pinned 1.3.

 

[desinr-gal]

so you didn't read what i wrote, got it

I did. I just disagree. Your points are like those tv commercials for drugs. "dont take if allergic"
A person cannot know what the effects of jumping up in their dose will have until they've done that. I have been reading the sub reddits for months seeing peoples stories. That is why I am very precise and slow in titrating. The ER visits and hospitalizations are happening.

 

[BellyD]

Yup, completely agree slow and grow. I started feeling the sensitive skin after 5mg of Reta. Everyone will have different results and responses.

 

[Waclive]

yes There is no other explanation. I had been pinning 1.2 of reta, and yesterday I pinned 1.3.

Have you noticed that happening at any other dosages?

 

[yrrdead]

Damn, a couple of them had 4 mg to start. Crazy.

Yeah some of the trials were/are spicy. Shoot even the guy that recently joined here is still scheduled for almost another year of 12mg and he's already in normal bmi range (flawed I know)

 

[Waclive]

Yeah some of the trials were/are spicy. Shoot even the guy that recently joined here is still scheduled for almost another year of 12mg and he's already in normal bmi range (flawed I know)

I would like to see some studies with people within a normal BMI take microdoses to study the insulin sensitivity affects and visceral fat.

 

[bogardbilla]

Damn, a couple of them had 4 mg to start. Crazy.

One of the studies referenced (this one: https://www.sciencedirect.com/science/article/pii/S1550413122003126 ) had an interesting titration schedule of 0.1mg, 0.3mg, 1mg, 3mg, 4.5mg, 6mg which is quite different from other studies. I would guess that this study was one of the very early ones, since it included both obese mice as well as human subjects.

In humans, doses of 0.1mg, 0.3mg and 1mg did not show statistically significant weight loss after one dose. 3mg, 4.5mg and 6mg showed a substantial statistically significant weight loss after one dose, and for 4.5mg and 6mg the weight loss persisted at those same levels for up to 45 days after that single dose!

My guess is that the results of that study are the reason why big clinical trials started at 2mg.

 

[lessthanhalf]

In response more to the original post than some of the comments.
There is a reason to increase the dose to or towards the standard maximum dose, that is strongly supported by the scientific evidence.
Most people taking these medications have significant problems with obesity, this does not apply as much to bodybuilders taking it or those who are younger than 40 or 50 or those who are only overweight. But the people with longstanding significant obesity , are most of the time at significant risk for cardiovascular disease, partly as obesity itself is a significant risk factor and also as high blood pressure, impaired glucose tolerance or diabetes, high cholesterol levels and lower levels of exercise, are strongly associated with obesity and the development of cardiovascular disease and stroke.
GLP medications ( less/not proven for retatrutide at this point ) reduce the chances of heart attack, stroke, heart failure , cardiovascular caused death, and death from all causes. As well as reduced blood pressure, reduced blood sugar and reduced cholesterol levels. Given that these are the commonest causes of death and disability as people age, this effect from GLP medications increases the chances of surviving in good health as you age. The doses of semaglutide and tirzepatide that have been proven to have these effects are the doses used in the trials, 2.4mg or lower if not tolerated for semaglutide, and 15mg for tirzepatide. The effect on improving these outcomes is partly due to the weight loss but the reductions in these levels and events is independent of weight loss, so the chances of these things happening is still reduced even if not much weight loss occurs.
GLP medications may also reduce the risks of developing alzheimer's disease, although recent studies suggest this may not be true, but there are more trials still underway. They also reduce the risks of developing quite a large number of cancers, including the most common ones, but may or may not increase the risks of thyroid and kidney cancer.
Lower doses of GLP medications will still have beneficial effects, but it is reasonable to assume that lower doses will have lesser effects. Demonstrating these effects requires large numbers of patients and long studies, and are therefore very expensive, so it is unlikely studies will be done at lower doses to prove this one way or another.
TLDR Taking GLP medications long term reduce the chances of most of the bad things that can happen to you or kill you as you get older, there is no reason to believe that lower doses are equally effective at doing this.
Increasing doses slowly is generally a good idea, and probably more important when it is being done without medical supervision, which applies to a lot of the people on this forum, but especially for older persons with significant obesity there are good reasons to increase the dose to the standard maximum dose.

 

[desinr-gal]

Have you noticed that happening at any other dosages?

I have had rise in BPM with Reta, since I got to 2mg? from 60 up to 70-80. It was a surprise to see 100-109

 

[ConnieL]

When I started GLP-1, it was with a compounding pharmacy. I started at their suggested dose and was so sick for three weeks. I felt like I had the flu or something worse. My blood pressure dropped, I passed out, and I ended up with a cut on my head and a wrist broken in three places plus a week in the hospital. That was the first time I had encountered dosage gone wrong.

Fortunately, since then I have discovered the wonderful gray market and also plenty of educational sources to guide me along. I am over 60, and I have lost 25 pounds since July using Reta. I am finally experiencing less joint pain and feel so much better about myself. I have carried that weight for about 30 years and spent thousands of dollars trying to lose it.

My family rats are now using GLP and they started at 5 units, and they are moving up very slowly. They have all successfully lost weight and had little to no side effects. I recommend everyone to follow what your body is telling you.

I do recommend that you read everything you can from well-informed people. But be careful and do not make decisions after just reading 2-3 or more articles from just one source. I have discovered lots of variations, and I recommend you try to find out what experiences someone has had under what circumstances before following guidelines.

Good luck. I am on to more peptide studies to help with some of these aging issues. I have had 2 surgeries on my wrist, and I really need to know how to get it healed!!!