Reta users - anyone experience increase in appetite initially?

[tendency]

So my wife started Reta a couple weeks ago at .5mg 2x/week. She's noticed a slight increase in her appetite at times along with some additional eating. Is this common for folks when they start off at a low initial dose?

 

[Such1943]

I was on semaglutide for 3 months at 1 mg per week, but after my prescription coupon expired, I switched to Reta. My appetite came back after a week. I started at 1 mg once a week, then increased to twice a week. Each week, I raised both doses by 1 mg until I found that 3 mg twice a week provided similar appetite suppression. I’ve now settled at 4 mg on Mondays and 5 mg on Thursdays. I titrated pretty fast. I haven’t tried a 9 mg single dose yet. I’m pretty sure it would make me sick.

There’s a chart circulating that compares receptor activation strength among the big three, and Reta ranks as the weakest for GLP-1 activation, which explains what she’s experiencing. I’d suggest starting at 1 mg twice a week and adjusting from there.

 

[tendency]

I was on semaglutide for 3 months at 1 mg per week, but after my prescription coupon expired, I switched to Reta. My appetite came back after a week. I started at 1 mg once a week, then increased to twice a week. Each week, I raised both doses by 1 mg until I found that 3 mg twice a week provided similar appetite suppression. I’ve now settled at 4 mg on Mondays and 5 mg on Thursdays. I titrated pretty fast. I haven’t tried a 9 mg single dose yet. I’m pretty sure it would make me sick.

There’s a chart circulating that compares receptor activation strength among the big three, and Reta ranks as the weakest for GLP-1 activation, which explains what she’s experiencing. I’d suggest starting at 1 mg twice a week and adjusting from there.

Good stuff thanks for the info; I'll talk to the wife about raiding her dose.

 

[zpped]

So my wife started Reta a couple weeks ago at .5mg 2x/week. She's noticed a slight increase in her appetite at times along with some additional eating. Is this common for folks when they start off at a low initial dose?

Is she gaining weight? If not, it doesn't really matter if she has more appetite. Most people have more appetite on reta than other glps.

There’s a chart circulating that compares receptor activation strength among the big three, and Reta ranks as the weakest for GLP-1 activation, which explains what she’s experiencing.

That chart is completely irrelevant to real world effects. It doesn't explain anything because it doesn't apply to how the drug works in a real human body.

 

[EXTRA TERRESTRIAL]

Does the chart show relative effects? I'd be interested in seeing that.

 

[Such1943]

[Imported image pending local asset: attachments-looking-for-an-infographic-comparing-glp-1-gip-and-glucagon-v0-5h6ybguk3brf1-webp.9546]

LY3437943 (Retatrutide)

Source: Wu et al. = Eli Lilly scientists; Diabetes, Obesity and Metabolism = peer-reviewed medical journal; 2024 = year published; DOI: 10.1111/dom.15803 = unique ID to find the paper online; Table S2

AI laymen terms breakdown, because its hard for me to follow...

Drug GLP-1R (Appetite) GIPR (Insulin Boost) GCGR (Fat Burn) Semaglutide (Ozempic) EC₅₀ = 0.35 nM ← Best (lowest) Eₘₐₓ = 105–109% EC₅₀ > 995 nM ← No effect Eₘₐₓ = ND EC₅₀ > 9950 nM ← No effect Eₘₐₓ = ND Tirzepatide (Mounjaro) EC₅₀ = 6.95 nM ← Weakest Eₘₐₓ = 107–117% ← Strongest EC₅₀ = 0.346 nM ← Good Eₘₐₓ = 100–104% EC₅₀ = 4060 nM ← Very weak Eₘₐₓ = 80% Retatrutide EC₅₀ = 0.775 nM ← 2nd best Eₘₐₓ = 110–112% ← Strong EC₅₀ = 0.064 nM ← Best (lowest!) Eₘₐₓ = 103–104% EC₅₀ = 5.79 nM ← Best (only one that works well) Eₘₐₓ = 104%

Receptor Winner Why GLP-1R Semaglutide Lowest EC₅₀ = needs tiniest dose GIPR Retatrutide Lowest EC₅₀ by far = super strong GCGR Retatrutide Only one with strong effect

You Take Same GLP-1R Effect As 1 mg Semaglutide 0.45 mg Retatrutide 1 mg Tirzepatide 9 mg Retatrutide

Semaglutide is 2.2× stronger than Retatrutide → need less Retatrutide.

Tirzepatide is 9× weaker → need 9× more Retatrutide.

That chart is completely irrelevant to real world effects. It doesn't explain anything because it doesn't apply to how the drug works in a real human body.

If this is all garbage, I'll delete for misinformation. Cannot trust everything on the internet.

 

[zpped]

If this is all garbage, I'll delete for misinformation. Cannot trust everything on the internet.

The key to the problem is in the chart title "in vitro assay".

So it's not that the data is wrong. It's that it doesn't mean what people think. In Vitro means in a test tube. And what something does in a test tube is not the same thing as how it acts in the real body. It's too complicated.

 

[Such1943]

"in vitro assay"

Good catch, I did not notice, but agree. It's clear why I’m not a Medicinal Chemist. Thanks for setting me straight. Like most things, take it with a grain of salt.

 

[nonyabizznez]

View attachment 9546

LY3437943 (Retatrutide)

Source: Wu et al. = Eli Lilly scientists; Diabetes, Obesity and Metabolism = peer-reviewed medical journal; 2024 = year published; DOI: 10.1111/dom.15803 = unique ID to find the paper online; Table S2

AI laymen terms breakdown, because its hard for me to follow...

Drug GLP-1R (Appetite) GIPR (Insulin Boost) GCGR (Fat Burn) Semaglutide (Ozempic) EC₅₀ = 0.35 nM ← Best (lowest) Eₘₐₓ = 105–109% EC₅₀ > 995 nM ← No effect Eₘₐₓ = ND EC₅₀ > 9950 nM ← No effect Eₘₐₓ = ND Tirzepatide (Mounjaro) EC₅₀ = 6.95 nM ← Weakest Eₘₐₓ = 107–117% ← Strongest EC₅₀ = 0.346 nM ← Good Eₘₐₓ = 100–104% EC₅₀ = 4060 nM ← Very weak Eₘₐₓ = 80% Retatrutide EC₅₀ = 0.775 nM ← 2nd best Eₘₐₓ = 110–112% ← Strong EC₅₀ = 0.064 nM ← Best (lowest!) Eₘₐₓ = 103–104% EC₅₀ = 5.79 nM ← Best (only one that works well) Eₘₐₓ = 104%

Receptor Winner Why GLP-1R Semaglutide Lowest EC₅₀ = needs tiniest dose GIPR Retatrutide Lowest EC₅₀ by far = super strong GCGR Retatrutide Only one with strong effect

You Take Same GLP-1R Effect As 1 mg Semaglutide 0.45 mg Retatrutide 1 mg Tirzepatide 9 mg Retatrutide

If this is all garbage, I'll delete for misinformation. Cannot trust everything on the internet.

Looking at this you'd think Tirzepatide performs the worst yet it beats Semaglutide hands down:

In a head-to-head human study (SURMOUNT-5), participants on tirzepatide lost an average of 47% more weight relative to those on semaglutide over 72 weeks.

Other trials show Tirzepatide out performs Semaglutide in glucose control and lowering A1c (.15 to .45 add'l).

In a world of no Tirzepatide if happily take Semaglutide though. Currently I'm taking Semaglutide (in maintenance) because I bought kits as a plan B (if Tirz became ineffective... which it didn't). My GFR is increasing with every set of labs so I'm going to stick with Sema a bit to see if kidney improvement continues. That would be a non scale victory! (stage 3 kidney disease).