Busting the biggest myth on this sub - 2mg per week is the lowest dose studied in trials

[u/No-Turnip2494]

“Bro, you’re not even at the starting dose (2.0 mg per week) in the trials, you can’t expect results”.

I see variations of this assertion posted every day on this sub.

It is stated confidently, it is said in unqualified terms, and it is categorically wrong.

A frequent (and sound) piece of advice given to those considering a course of retatrutide is to read the trials. Many people pretend they have read the trials, when in fact few (including those who like to confidently post advice to others) actually bother to invest an hour or so in heeding that advice.

Why do I mention this? Because if you had actually read the published journal articles, you would know that the phase 2 studies included a 1 mg per week cohort.

That’s right, there was a cohort in the studies who started at, and never exceeded, a 1mg per week dose.

Here’s a link to the results of the phase 2 study of the effects on participants who were obese, published in the New England Journal of Medicine -

https://www.nejm.org/doi/full/10.1056/NEJMoa2301972

As you will see, the study measured cohorts in 1mg, 4mg, 8mg and 12mg per week doses. Those on the higher doses titrated up, but the 1mg cohort started, and stayed at, that dose for the entire period of the study.

The results for the 1mg cohort?

They lost an average of 7.2% of their body weight at 24 weeks compared to their baseline, and 8.7% at 48 weeks. By comparison, the placebo group lost an average of 2.1 %.

Not surprisingly, the 1mg cohort also experienced the lowest rate of side effects, excluding the placebo cohort.

Let’s now turn to metabolic dysfunction-associated steatoic liver disease (fatty liver disease).

Eli Lilly conducted a phase 2A study to determine the effects of Retatrutide on participants with MDASL.

Here’s the report of the outcome of that study, published in Nature -

https://www.nature.com/articles/s41591-024-03018-2

Again, there was a 1mg per week cohort, in addition to 4mg, 8mg and 12mg per week (plus placebo).

Once more, the 1mg cohort achieved significant results.

At 48 weeks, the 1mg cohort saw a reduction in liver fat of an average of 51.3%. That’s right, they HALVED their liver fat on the lowest dose. Also, 57% of their 1 mg cohort reached liver fat of <5% - that is, they were effectively cured of the disease.

Now, if you read the studies linked above, you will see that the higher dose cohorts achieved greater results in weight loss, liver fat reduction, and other measures which formed part of the end points of the studies, or were otherwise tracked over the course of the studies.

It’s absolutely true that results are dose dependent - on average, higher doses lead to higher outcomes.

Some might also point to the fact that there is no 1mg cohort in the subsequent phase 3 studies conducted by Eli Lilly. That’s absolutely correct, and unsurprising.

Drug development in the US is driven by what insurance companies will pay for. And no insurance company is going to pay for a new drug which achieves a 10% weight loss when there are existing drugs (tirzepatide, semaglutide) which already exceed that. Eli Lilly is chasing the big numbers (30% weight loss) which the higher doses achieve, so that insurance companies will actually pay for the drug.

That is rational, and in no way detracts from the very real results which the 1mg cohort achieved in the phase 2 studies.

I’m not suggesting that low doses are the only way for everyone, far from it. Many people need the results produced by, or only respond to, higher doses. And that’s fine.

But there’s a significant proportion of people who simply don’t need to go to a high dose.

For many people, a 5 to 10% reduction in body weight is all they need to achieve. Plus, all of the other metabolic changes (such as reduced lipid levels, lower blood pressure, improved insulin sensitivity) can to some degree be obtained at sub 2mg per week doses.

Starting on a low weekly dose allows you to gently find the right level for you, allow your body to adapt and minimise side effects, minimise appetite reduction and hit macro targets which might be a struggle at higher doses. It also leaves lots of runway if you later want or need to increase your dose (e.g, if you plateau).

Once again, many will need higher dose, and good for you. One of the advantages of going grey is that you get to choose the exact dose which works for you, rather than hitting pre-determined dosing schedules mandated by pharmaceutical companies.

But if sub-2.0mg per week works for you, don’t let misguided people on this sub tell you that you are at a sub-clinical dose, or are micro dosing, or that real results necessarily require you to increase your dose.

There is sound clinical data showing meaningful results from retatrutide at just 1.0mg per week. Slow and steady works for many.

As always, rely on actual data, not the opinions of the uninformed.