First Reta Dose for a 146 kg Friend?

[skaylife]

Hey everyone,

A close buddy of mine is at 146kg (322lbs). For a couple of years he's been on Ozempic, maxed out on the dose. The most he ever managed to drop was 20kgs. Then it came back, and right now the medication isn't doing anything for him anymore. He's interested in giving Reta a shot and came to me for dosing guidance. Problem is, I've never used Reta myself. A while back I gave it a try for several weeks, but it didn't agree with me. I quit after 3 days of severe diarrhea.

I'm familiar with how the Reta protocol works. That said, I've never been anywhere near that heavy, so I have no clue what his starting dose ought to be. Any solid advice would be greatly appreciated.

Oh, almost left this out! He's also dealing with diabetes II.

 

[eidos]

Worth pointing out: in clinical trials, retatrutide's glucagon receptor effects only become clearly apparent starting at 8mg/week (for me, 7.5 brought blood sugar down substantially). That's the piece that matters most when it comes to diabetes.

My own approach was to begin with 2.5mg just to see how I'd react, then step the dose up over time until reaching 10mg/week. Now my blood sugar reads under 100 mg/dl, and that's even post-meal. With my CGM, the projected HbA1c comes out at 6.5%, compared to 10.5 back in February when I was on Tirz and hadn't yet made the switch to Reta. BMI has gone from 31-32 down to 27-28.

 

[skaylife]

eidos said:

Worth pointing out: in clinical trials, retatrutide's glucagon receptor effects only become clearly apparent starting at 8mg/week (for me, 7.5 brought blood sugar down substantially). That's the piece that matters most when it comes to diabetes.

My own approach was to begin with 2.5mg just to see how I'd react, then step the dose up over time until reaching 10mg/week. Now my blood sugar reads under 100 mg/dl, and that's even post-meal. With my CGM, the projected HbA1c comes out at 6.5%, compared to 10.5 back in February when I was on Tirz and hadn't yet made the switch to Reta. BMI has gone from 31-32 down to 27-28.

I appreciate the suggestion. My own reasoning was that beginning at 0.5~1mg, which is what the majority of users do, would likely be insufficient for someone his size. I considered maybe beginning with 2mg, then after 1 month moving up to 4 and continuing that way until we identify the dose that works well. Still, I did not feel confident offering any recommendation before checking what people with actual Reta research experience think.

Initially he too was sceptical about Reta, and he worried about long-term unexpexted consequences that are not yet known. He asked: what if, 10 years from now, he develops other health issues caused by Reta use? He is already 61 years old and works a passive office job. Walking 2 steps takes 2 seconds. I had to ask him whether he really expected to live 10 more years at that weight, age and condition? Saying that to him was not easy. But as a friend I had to confront him with truth. I hope Reta allows him to live healthier and longer. In Belgium insurance pays only semaglutide. For Mounjaro he must pay full price, and 10mg costs €400/month, which he can't afford. Grey market is the only good solution for him at the moment. I can even pay it for him, if he accepts. But I don't think he will.

 

[eidos]

skaylife said:

eidos said:

Worth pointing out: in clinical trials, retatrutide's glucagon receptor effects only become clearly apparent starting at 8mg/week (for me, 7.5 brought blood sugar down substantially). That's the piece that matters most when it comes to diabetes.

My own approach was to begin with 2.5mg just to see how I'd react, then step the dose up over time until reaching 10mg/week. Now my blood sugar reads under 100 mg/dl, and that's even post-meal. With my CGM, the projected HbA1c comes out at 6.5%, compared to 10.5 back in February when I was on Tirz and hadn't yet made the switch to Reta. BMI has gone from 31-32 down to 27-28.

I appreciate the suggestion. My own reasoning was that beginning at 0.5~1mg, which is what the majority of users do, would likely be insufficient for someone his size. I considered maybe beginning with 2mg, then after 1 month moving up to 4 and continuing that way until we identify the dose that works well. Still, I did not feel confident offering any recommendation before checking what people with actual Reta research experience think.

Initially he too was sceptical about Reta, and he worried about long-term unexpexted consequences that are not yet known. He asked: what if, 10 years from now, he develops other health issues caused by Reta use? He is already 61 years old and works a passive office job. Walking 2 steps takes 2 seconds. I had to ask him whether he really expected to live 10 more years at that weight, age and condition? Saying that to him was not easy. But as a friend I had to confront him with truth. I hope Reta allows him to live healthier and longer. In Belgium insurance pays only semaglutide. For Mounjaro he must pay full price, and 10mg costs €400/month, which he can't afford. Grey market is the only good solution for him at the moment. I can even pay it for him, if he accepts. But I don't think he will.

Here in France it's the same situation, only my pharmacy charges slightly less since they don't add a markup. I moved over to Grey and haven't looked back.

How many psychologists does it take to change a light bulb?

Just one. But the light bulb has to want to change.

Click to expand...

 

[BBA1969]

My sister began Retatrutide with my help. Before that, she had used Ribelsus (oral Semaglutide). For the first 4 weeks we used 1mg to let her adapt. Her response was quick, so 1mg continued for 6 weeks in total, after which we moved to 1.5mg. 4 months in, she remains at 2mg weekly and in all likelihood won't change that until she hits her target weight (8kg left).

Once that happens, my suggestion will likely be a switch to Tirzepatide or cagrisema at the smallest dose, for maintenance.

What I'd recommend is beginning very low, no more than 1 to 2mg, for a few weeks, then increasing by 1mg each time.

Alternatively, grey Tirzepatide following the Mounjaro path > 2.5 - 5 - 7.5 -10 and so on is an option. If losing weight is the primary goal, Tirzepatide is unmatched as far as I'm concerned.

DM me anytime

 

[Mochizuki0124]

For him, I'd say begin at .5 no matter what GLP history he has. After 1 week at .5, increase by .5 each week until either a sweet spot shows up or 4mg is reached, whichever happens first. Once at 4mg, I'd hold there for a few weeks prior to any further increase.

 

[Don]

eidos said:

Worth pointing out: in clinical trials, retatrutide's glucagon receptor effects only become clearly apparent starting at 8mg/week (for me, 7.5 brought blood sugar down substantially). That's the piece that matters most when it comes to diabetes.

My own approach was to begin with 2.5mg just to see how I'd react, then step the dose up over time until reaching 10mg/week. Now my blood sugar reads under 100 mg/dl, and that's even post-meal. With my CGM, the projected HbA1c comes out at 6.5%, compared to 10.5 back in February when I was on Tirz and hadn't yet made the switch to Reta. BMI has gone from 31-32 down to 27-28.

I'm not convinced the glucagon effect only becomes meaningful once you hit 8 mg.

Looking at the liver fat findings, there was roughly a 51% decrease at 1 mg and 59% at 4 mg by week 48. The largest step up occurred from 4 mg to 8 mg at 82%, yet a clear and meaningful effect was already present below 8 mg, and at 12mg it only rose slightly to 86%

From my reading, these results point to the glucagon part becoming more apparent as the dose goes up, rather than abruptly turning on at 8 mg.

I also wouldn't point to better glucose control as proof of a glucagon effect. Glucagon by itself generally raises blood glucose. The HbA1c improvement is more plausibly explained by retatrutide's overall actions: GLP-1, GIP, weight loss, lower food intake, and greater insulin sensitivity

 

[Don]

Even at 146 kg, body weight alone wouldn't make me choose a higher starting dose. My approach would be to begin low and then raise it on the usual schedule, every 2-4 weeks. When it comes to Reta, what typically caps the dose is tolerance rather than weight.

And if Ozempic has quit working, I wouldn't draw big conclusions from that. A lot of people hit a plateau on Sema yet still do really well when they switch to Tirz or Reta.

The error I notice most often is people forcing the titration upward because they're eager to reach the "effective" doses quickly. I'd prefer to spend a few extra weeks and remain on the medication than to escalate aggressively and wind up managing side effects. In most cases, those who get into difficulty do so from climbing too fast, not from having begun too low.

 

[skaylife]

BBA1969 said:

My sister began Retatrutide with my help. Before that, she had used Ribelsus (oral Semaglutide). For the first 4 weeks we used 1mg to let her adapt. Her response was quick, so 1mg continued for 6 weeks in total, after which we moved to 1.5mg. 4 months in, she remains at 2mg weekly and in all likelihood won't change that until she hits her target weight (8kg left).

Once that happens, my suggestion will likely be a switch to Tirzepatide or cagrisema at the smallest dose, for maintenance.

What I'd recommend is beginning very low, no more than 1 to 2mg, for a few weeks, then increasing by 1mg each time.

Alternatively, grey Tirzepatide following the Mounjaro path > 2.5 - 5 - 7.5 -10 and so on is an option. If losing weight is the primary goal, Tirzepatide is unmatched as far as I'm concerned.

DM me anytime

Appreciate it. Tirz actually worked better for me than Reta did. I quit Reta after a 2 week trial because it made me sick, whereas 5mg of Tirz got me to my GW in 8 months with no titration needed. He picked Reta on his own. I could bring it up again. The thing is, he has a compensation mechanism. He's convinced himself that he doesn't eat that much. According to him, his weight gain comes from high cortisol. That might explain overeating. Still, overeating the wrong foods without burning any calories is what causes weight gain. When I say this to him, it doesn't get through. We shall see

 

[skaylife]

Don said:

eidos said:

Worth pointing out: in clinical trials, retatrutide's glucagon receptor effects only become clearly apparent starting at 8mg/week (for me, 7.5 brought blood sugar down substantially). That's the piece that matters most when it comes to diabetes.

My own approach was to begin with 2.5mg just to see how I'd react, then step the dose up over time until reaching 10mg/week. Now my blood sugar reads under 100 mg/dl, and that's even post-meal. With my CGM, the projected HbA1c comes out at 6.5%, compared to 10.5 back in February when I was on Tirz and hadn't yet made the switch to Reta. BMI has gone from 31-32 down to 27-28.

I'm not convinced the glucagon effect only becomes meaningful once you hit 8 mg.

Looking at the liver fat findings, there was roughly a 51% decrease at 1 mg and 59% at 4 mg by week 48. The largest step up occurred from 4 mg to 8 mg at 82%, yet a clear and meaningful effect was already present below 8 mg, and at 12mg it only rose slightly to 86%

From my reading, these results point to the glucagon part becoming more apparent as the dose goes up, rather than abruptly turning on at 8 mg.

I also wouldn't point to better glucose control as proof of a glucagon effect. Glucagon by itself generally raises blood glucose. The HbA1c improvement is more plausibly explained by retatrutide's overall actions: GLP-1, GIP, weight loss, lower food intake, and greater insulin sensitivity

I wasn't intending to go straight from 4 to 8 either. Instead, I'd move up to 6 without changing anything else. Going from 4 to 8 is a huge leap.

 

[eidos]

Don said:

eidos said:

Worth pointing out: in clinical trials, retatrutide's glucagon receptor effects only become clearly apparent starting at 8mg/week (for me, 7.5 brought blood sugar down substantially). That's the piece that matters most when it comes to diabetes.

My own approach was to begin with 2.5mg just to see how I'd react, then step the dose up over time until reaching 10mg/week. Now my blood sugar reads under 100 mg/dl, and that's even post-meal. With my CGM, the projected HbA1c comes out at 6.5%, compared to 10.5 back in February when I was on Tirz and hadn't yet made the switch to Reta. BMI has gone from 31-32 down to 27-28.

I'm not convinced the glucagon effect only becomes meaningful once you hit 8 mg.

Looking at the liver fat findings, there was roughly a 51% decrease at 1 mg and 59% at 4 mg by week 48. The largest step up occurred from 4 mg to 8 mg at 82%, yet a clear and meaningful effect was already present below 8 mg, and at 12mg it only rose slightly to 86%

From my reading, these results point to the glucagon part becoming more apparent as the dose goes up, rather than abruptly turning on at 8 mg.

I also wouldn't point to better glucose control as proof of a glucagon effect. Glucagon by itself generally raises blood glucose. The HbA1c improvement is more plausibly explained by retatrutide's overall actions: GLP-1, GIP, weight loss, lower food intake, and greater insulin sensitivity

I never brought up a threshold effect — that reading is yours.

What draws me to Reta is exactly this: its glucagon agonism seems paradoxical, yet it allows for control when GLP-1 agonism alone doesn't get the job done.

 

[lessthanhalf]

A high starting weight mainly means that, as time goes on, titrating up toward a maximum of 12 mg will probably be necessary and sensible.

If he is still on semaglutide at 2.4 mg, then a reta starting dose of 4mg ought to be okay; however, if sema has been off for some time, beginning at 2mg would be the safer route. Reta's side effect profile differs somewhat from sema's—things like a greater rise in heart rate and skin sensitivity can occur—though nausea and vomiting tend to be less than with sema.

Type 2 diabetes is another factor to weigh. On their own, GLP drugs seldom trigger hypoglycaemia, yet when they are used alongside other diabetes medications the chance goes up, so glucose should be monitored closely both when starting and when increasing the dose. It is also unfortunate that people with diabetes tend to lose less weight than those without it—just to keep expectations realistic—so perhaps an average of 15 - 20 % instead of 29% for non diabetics. His response to semaglutide was actually quite good given that non diabetics get about 15-18%, and 20/146 works out to 13.8%.

The usual approach of starting at 2mg and raising by 2mg every 4 weeks is likely to be fine; since 2.4 of sema was tolerated, it is very unlikely that 12mg of reta would bring worse side effects.

I also have some rather grim 10 year heart attack risk figures, even after 80 kilos of weight loss. Bringing those risks down is not only about weight—good blood glucose control matters, and reta will help there—but also about making sure blood pressure and lipids are treated optimally, which can lower those risks a great deal, at least by a factor of 2.

If I had to guess, he will lose some weight, but probably not more than 15-20% on reta. Even if that falls far short of ideal, it can still dramatically alter health risks and is worth working hard to maintain. That means staying on it rather than stopping as happened with the sema, even if the results are somewhat disappointing. Once he reaches a genuine plateau in a year or so, adding cagri or eloralintide might be an option. At least with grey reta the cost is not much of a concern compared with the legit versions. And at that level of overall health risk, the dangers of grey peptides or combination therapies are likely to be far lower than those of untreated obesity.

 

[skaylife]

lessthanhalf said:

A high starting weight mainly means that, as time goes on, titrating up toward a maximum of 12 mg will probably be necessary and sensible.

If he is still on semaglutide at 2.4 mg, then a reta starting dose of 4mg ought to be okay; however, if sema has been off for some time, beginning at 2mg would be the safer route. Reta's side effect profile differs somewhat from sema's—things like a greater rise in heart rate and skin sensitivity can occur—though nausea and vomiting tend to be less than with sema.

Type 2 diabetes is another factor to weigh. On their own, GLP drugs seldom trigger hypoglycaemia, yet when they are used alongside other diabetes medications the chance goes up, so glucose should be monitored closely both when starting and when increasing the dose. It is also unfortunate that people with diabetes tend to lose less weight than those without it—just to keep expectations realistic—so perhaps an average of 15 - 20 % instead of 29% for non diabetics. His response to semaglutide was actually quite good given that non diabetics get about 15-18%, and 20/146 works out to 13.8%.

The usual approach of starting at 2mg and raising by 2mg every 4 weeks is likely to be fine; since 2.4 of sema was tolerated, it is very unlikely that 12mg of reta would bring worse side effects.

I also have some rather grim 10 year heart attack risk figures, even after 80 kilos of weight loss. Bringing those risks down is not only about weight—good blood glucose control matters, and reta will help there—but also about making sure blood pressure and lipids are treated optimally, which can lower those risks a great deal, at least by a factor of 2.

If I had to guess, he will lose some weight, but probably not more than 15-20% on reta. Even if that falls far short of ideal, it can still dramatically alter health risks and is worth working hard to maintain. That means staying on it rather than stopping as happened with the sema, even if the results are somewhat disappointing. Once he reaches a genuine plateau in a year or so, adding cagri or eloralintide might be an option. At least with grey reta the cost is not much of a concern compared with the legit versions. And at that level of overall health risk, the dangers of grey peptides or combination therapies are likely to be far lower than those of untreated obesity.

Thanks for laying all of that out.

Sema isn't doing nothing for him, but what he does get from it is so minor it's hardly worth bringing up, and he hits a ceiling very quickly. Around 10 weeks gets him down 7-8 kgs, then he stalls. He keeps injecting for another 2 months with nothing moving, and the doctor tells him to take a month off before restarting. That month off, though, puts the same amount back on him, sometimes more.

My plan is for him to begin at 2mg and go up by 2mgs every 4 weeks until his sweet spot shows up. Bringing in Cagri or Elarolintide is too big a jump right now. Still, I'll hold onto the idea for when we reach that point.

From what I understand, he tests his blood sugar daily. Depending on how that shifts, would you mind if I came back with more questions?

 

[skaylife]

Don said:

Even at 146 kg, body weight alone wouldn't make me choose a higher starting dose. My approach would be to begin low and then raise it on the usual schedule, every 2-4 weeks. When it comes to Reta, what typically caps the dose is tolerance rather than weight.

And if Ozempic has quit working, I wouldn't draw big conclusions from that. A lot of people hit a plateau on Sema yet still do really well when they switch to Tirz or Reta.

The error I notice most often is people forcing the titration upward because they're eager to reach the "effective" doses quickly. I'd prefer to spend a few extra weeks and remain on the medication than to escalate aggressively and wind up managing side effects. In most cases, those who get into difficulty do so from climbing too fast, not from having begun too low.

I apologize for the brief reply earlier today. Work was starting and I was about to head out the door. Appreciate the guidance, mate. Sema gives him only a mild effect, though it's not really worth discussing.

I'm with you on this, and I've also watched people close to me dive in fast and wind up sorry. They dropped a lot of weight quickly on high doses, but dealt with things like throwing up, feeling sick..... I'll be there for him the whole way and won't allow rushing. He might get mad at me. That doesn't worry me, though. I can outrun him