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

| 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.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.
The key to the problem is in the chart title "in vitro assay".If this is all garbage, I'll delete for misinformation. Cannot trust everything on the internet.
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."in vitro assay"
Looking at this you'd think Tirzepatide performs the worst yet it beats Semaglutide hands down: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.
