lessthanhalf said:
Zelmar702 said:
Just so you know — over on YT there's a physician who also uses GLP meds, Dr. Kevin Joseph, and he put out a video covering exactly this topic not long ago. The main takeaways are:
- Turning On the Glucagon Receptor: Retatrutide works as a triple agonist, hitting GIP, GLP-1, and glucagon [00:53]. Below 4 mg, only GIP and GLP-1 get activated, so it basically behaves like a pricey Tirzepatide [01:42]. The glucagon receptor, which drives greater fat burning and liver clearing, needs a higher concentration before it switches on, and clinical markers indicate it kicks in exactly at the 4 mg threshold [01:31, 03:35].
- Evidence That It's Active: According to Dr. Joseph, the mild effects that show up at 4 mg — a particular tingling of the skin (dysesthesia), a small rise in heart rate, and a 57% reduction in liver fat — act as clinical confirmation that the glucagon receptor is now engaged [02:15, 03:23].
- Remarkably Well Tolerated: Side effects at 4 mg of Retatrutide are extremely uncommon. In the trials, only 4.1% of participants dropped out because of side effects at 4 mg (practically the same as the 4.9% seen in the placebo arm), while the 12 mg dose had an 18% dropout rate [04:12, 04:29].
His overall message is that pushing the dose as high as possible isn't always necessary; at 4 mg a patient gets the distinct advantages of all three receptor targets safely, and tolerability stays on par with placebo [
04:42,
05:40].
Apologies for drifting a bit off the main subject, but this particular guy comes up fairly often, and it looked like the OP was replying to something he'd said. In my view, what he claims isn't grounded in the science we actually have.
The notion that a drug only "turns on" once you hit some specific dose, say 4mg, is complete nonsense — that isn't how pharmacology works in general, and it isn't how incretin receptors and their agonists behave either. Holding a medical degree counts for nothing when someone gets the fundamentals of pharmacology wrong and doesn't bother reading the studies. As with every other GLP drug, reta's effects grow as the dose goes up, until a point where further increases stop adding useful benefit while possibly worsening side effects — and that point sits somewhere past 12mg.
There's nothing wrong with people sharing their personal takes on these medications, but once you're posting youtube videos and putting a Dr in front of your name, I think you take on an obligation to make sure what you're putting out there is scientifically accurate. I realize that's not really how the whole celebrity Doctor phenomenon in the US operates, where fame seems to correlate with how much BS gets said. Still, because of that Dr in front of the name, people are much more inclined to take his word for it, so it does matter.
The claim about effects only beginning at 4mg is especially strange, since reta — unlike sema or tirz — performs remarkably well at very low doses, where 1mg across a year produces an average of 9% weight loss, roughly matching the effect of 2.5-5mg of tirz. That makes reta at fairly low doses, hopefully with low side effect rates too, potentially a strong option for people using it for being overweight without needing to shed a lot of weight (as well as for those with severe obesity at higher doses). At 4mg it's more effective — no surprise there — with about 18% weight loss, and 12mg is more effective still, reaching up to 29% weight loss over a year. He isn't wrong that low doses of reta work pretty well, but the idea that glucagon receptors do nothing at 3mg and then abruptly kick in at 4mg simply isn't how the drug behaves. The examples he gives of effects that supposedly begin at 4mg are also invented out of nowhere. Dysesthesia/allodynia from reta is certainly dose related, but most people on 12mg don't experience it, and there's no particular dose at which it will or won't show up.
To answer the OP: low dose reta ( 1-4mg ) genuinely has a decent chance of getting you where you want to be, though it will take a year or a little longer. Assuming 1mg and 9% weight loss starting from a BMI of 28.3, you'd land at a bmi slightly above 25, and at 4mg with 18% you'd reach a bmi of 23. These are averages, of course, and responses to GLP drugs vary from person to person, but it's still helpful for setting reasonable expectations. Raising doses very slowly lowers the odds of sudden severe side effects, yet it can make weight loss slow enough that you feel like the progress you want to see isn't happening. Raising doses somewhat faster tends to deliver more satisfying weight loss sooner, but at the cost of greater risk of unexpected side effects. Unless you intend to climb all the way to 12mg just to fix a not-severe overweight problem a bit faster — which sounds like overkill — you're still looking at a year to get there. And if being overweight isn't causing you medical problems, staying conservative with dosing to keep risks as low as possible is probably the sensible approach.