Start dose Reta

[skaylife]

Hi friends,

A good friend of mine weighs 146kg (322lbs) and have been using Ozempic couple of years at highest dosage. He could ever lose 20kgs. But gained back and at the moment it doesn't help anymore. He wants to try Reta and asked me advice about dosage. But I am not a Reta user. Sometime ago tried Reta for a few weeks. But did not work for me. Stopped after getting 3 days long heavy diarrhea.

I know how Reta protocol is. But I didn't ever reach such a high weight and don't have any idea what should be his start dose? Good advice will be much appreciated.
Almost forgotten! He has also diabetes II.

 

[eidos]

It should be noted that the effect of retatrutide on the glucagon receptor is really felt from 8mg/week in clinical studies (7.5 significantly lowered my blood sugar). This is what is really important for diabetes.

I started at 2.5mg to test my reaction and then gradually increased the dose up to 10mg/week. My blood sugar level is below 100 mg/dl, even though it's after dinner. I have a CGM and it projects an HbA1c of 6.5% whereas I was at 10.5 in February, under Tirz and before switching to Reta. BMI from 31-32 to 27-28.

 

[skaylife]

It should be noted that the effect of retatrutide on the glucagon receptor is really felt from 8mg/week in clinical studies (7.5 significantly lowered my blood sugar). This is what is really important for diabetes.

I started at 2.5mg to test my reaction and then gradually increased the dose up to 10mg/week. My blood sugar level is below 100 mg/dl, even though it's after dinner. I have a CGM and it projects an HbA1c of 6.5% whereas I was at 10.5 in February, under Tirz and before switching to Reta. BMI from 31-32 to 27-28.

Thanks for your advice. I was also thinking that start doses like 0.5~1mg like most people do, should be too low for him. Thought may be start at 2mg and after a month titrate to 4 and so on unltil we find the good response dosage. But could not dare to give any advice without asking opinion of researchers with Reta experience.

At first he was also sceptisch about Reta and had concerns about long term unexpexted consequences which are not known yet. Asked, what if he after 10 years get some other health issues because of Reta use. He is already 61 years old and has a passive office job. Walking 2 steps takes 2 seconds. I had to ask him if he was expecting to live 10 more years at that weight, age and condition? It was not easy to say that to him. But as a friend I had to confront him with truth. I hope he can live healthier and longer thanks to Reta. In Belgium insurance pays only semaglutide. He has to pay full price for Mounjaro 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]

He has to pay full price for Mounjaro and 10mg costs €400/month which he can't afford.

Same thing in France, just a little cheaper at my pharmacy, which doesn't take a margin. I switched to Grey, and I have no regrets.

How many psychologists does it take to change a light bulb?
Just one. But the light bulb has to want to change.

 

[BBA1969]

I helped my sister get started on Retatrutide. She had a history on Ribelsus (oral Semaglutide). We started off on 1mg for 4 weeks for adaptation. She really responded right away so she stayed on 1mg for 6 weeks before going to 1.5mg. Now after 4 months she's still on 2mg per week and will likely stay there until she reaches her goal weight (8kg to go).
After that I will probably advise her to swith to Tirzepatide or cagrisema at a minimal dose for maintenance.

My advice is to start really low like 1 to 2mg max for a couple of weeks and then go up 1mg at a time.

Or you can get grey Tirzepatide and follow the Mounjaro route > 2.5 - 5 - 7.5 -10 and so on. If pure weightloss is the main driver, nothing beats Tirzepatide in my opinion.

Feel free to DM me 😉

 

[Mochizuki0124]

My recommendation is start at .5 regardless of his experience with GLP's. Do .5 1 week then titrate by .5 weekly until he finds a sweet spot or 4mg whichever comes first. I would stay at 4mg for a few weeks before going up again.

 

[Don]

It should be noted that the effect of retatrutide on the glucagon receptor is really felt from 8mg/week in clinical studies (7.5 significantly lowered my blood sugar). This is what is really important for diabetes.

I started at 2.5mg to test my reaction and then gradually increased the dose up to 10mg/week. My blood sugar level is below 100 mg/dl, even though it's after dinner. I have a CGM and it projects an HbA1c of 6.5% whereas I was at 10.5 in February, under Tirz and before switching to Reta. BMI from 31-32 to 27-28.

Not sure I agree that the glucagon effect only starts being relevant at 8 mg.

The liver fat data already showed around 51% reduction at 1 mg and 59% at 4 mg after 48 weeks. The biggest jump was between 4 mg and 8 mg 82%, but there was clearly a substantial effect before 8 mg as well and on 12mg it didn't increase much to 86%
To me, the data suggest that the glucagon component may become more noticeable at higher doses, but not that it suddenly switches on at 8 mg.

Also, I wouldn't use improved glucose control as evidence of a glucagon effect. Glucagon on its own tends to increase blood glucose. The HbA1c improvement is more likely the result of the overall effects of retatrutide: GLP-1, GIP, weight loss, reduced food intake, and improved insulin sensitivity

 

[Don]

At 146 kg I still wouldn't start higher just because of body weight. I would start low and up the dose normally every 2-4 weeks. With Reta, tolerance is usually the limiting factor, not weight

Also if Ozempic stopped working, I wouldn't read too much into that. Plenty of people plateau on Sema and still respond very well to Tirz or Reta

The biggest mistake I see is people rushing the escalation because they want to get to the "effective" doses as fast as possible. I would rather take an extra few weeks and stay on the drug than push too hard and end up dealing with side effects. Most people who run into trouble do so because they increase too fast, not because they started too low

 

[skaylife]

I helped my sister get started on Retatrutide. She had a history on Ribelsus (oral Semaglutide). We started off on 1mg for 4 weeks for adaptation. She really responded right away so she stayed on 1mg for 6 weeks before going to 1.5mg. Now after 4 months she's still on 2mg per week and will likely stay there until she reaches her goal weight (8kg to go).
After that I will probably advise her to swith to Tirzepatide or cagrisema at a minimal dose for maintenance.

My advice is to start really low like 1 to 2mg max for a couple of weeks and then go up 1mg at a time.

Or you can get grey Tirzepatide and follow the Mounjaro route > 2.5 - 5 - 7.5 -10 and so on. If pure weightloss is the main driver, nothing beats Tirzepatide in my opinion.

Feel free to DM me 😉

Thanks. I was also better responsive to Tirz than Reta. My 2 weeks Reta trial was ended with getting sick from it and reached my GW in 8 months at 5mg Tirz without titrating. Reta was his own choise. I can suggest once more. But he has a compensation mechanism. Convinced his own that he doesn't eat so much. He tells that his weight gain is related with high level of cortisol. May be a reason for eating too much. But eating too much wrong things without using any calories is a reason for gaining weight. Doasn't hear that when I tell it to him. We shall see

 

[skaylife]

Not sure I agree that the glucagon effect only starts being relevant at 8 mg.

The liver fat data already showed around 51% reduction at 1 mg and 59% at 4 mg after 48 weeks. The biggest jump was between 4 mg and 8 mg 82%, but there was clearly a substantial effect before 8 mg as well and on 12mg it didn't increase much to 86%
To me, the data suggest that the glucagon component may become more noticeable at higher doses, but not that it suddenly switches on at 8 mg.

Also, I wouldn't use improved glucose control as evidence of a glucagon effect. Glucagon on its own tends to increase blood glucose. The HbA1c improvement is more likely the result of the overall effects of retatrutide: GLP-1, GIP, weight loss, reduced food intake, and improved insulin sensitivity

I was also not planning to jump to 8 from 4. But to 6 in place. 4 to 8 is a very big step.

 

[eidos]

Not sure I agree that the glucagon effect only starts being relevant at 8 mg.

The liver fat data already showed around 51% reduction at 1 mg and 59% at 4 mg after 48 weeks. The biggest jump was between 4 mg and 8 mg 82%, but there was clearly a substantial effect before 8 mg as well and on 12mg it didn't increase much to 86%
To me, the data suggest that the glucagon component may become more noticeable at higher doses, but not that it suddenly switches on at 8 mg.

Also, I wouldn't use improved glucose control as evidence of a glucagon effect. Glucagon on its own tends to increase blood glucose. The HbA1c improvement is more likely the result of the overall effects of retatrutide: GLP-1, GIP, weight loss, reduced food intake, and improved insulin sensitivity

I didn't mention a threshold effect; that's your interpretation.

That is precisely what makes Reta so interesting: its agonism with glucagon, though counterintuitive, enables regulation in situations where GLP-1 agonism is insufficient.

 

[lessthanhalf]

The only real difference the high start weight has is that over time increasing doses towards maximum 12 mg is very likely to be needed and a good idea.

Assuming he is currently taking semaglutide at 2.4 mg , starting at 4mg of reta should be fine, but if sema has been stopped for a while, then starting at 2mg would be safer, reta does have some different side effects to sema like more increased heart rate and skin sensitivity. But has less nausea and vomiting than sema.

The other thing to consider is the type 2 diabetes. GLP drugs rarely cause hypoglycaemia on their own, but once you start combining it with other diabetes drugs, it is more likely, so careful glucose monitoring is needed with starting it and with dose increases. Unfortunately diabetes patients consistently lose less weight than non diabetics, just to keep expectations realistic , so maybe average of 15 - 20 % rather than 29% for non diabetics, and the response to semaglutide was actually pretty good considering it is about 15-18% for non diabetics, and 20/146 is 13.8%.

Doing the standard 2mg start and 2mg increases every 4 weeks is likely to be fine, the fact that 2.4 of sema was tolerated means it is very unlikely that 12mg of reta would have worse side effects.

I also have some pretty unpleasant 10 year heart attack risk numbers, even with 80 kilos of weight loss. Reducing those risks is not just weight , good blood glucose control, reta will help there, but also making sure blood pressure and lipids are optimally treated, can reduce those risks a lot , and at least by a factor of 2.

If I had to guess he is going to lose some weight , but not likely to be more than 15-20% on reta. Even if this is a long way from perfect it can dramatically change health risks and is worth trying hard to preserve it. By staying on it and not stopping like was done with the sema, even if the results are a bit disappointing. Once he gets to a real plateau in a year or so, adding in cagri or eloralintide might be an option. At least with grey reta the price is not much of an issue compared with the legit versions. And at that level of overall health risk, the risks of grey peptides or combination therapies are likely to be much lower than the untreated obesity.

 

[skaylife]

The only real difference the high start weight has is that over time increasing doses towards maximum 12 mg is very likely to be needed and a good idea.

Assuming he is currently taking semaglutide at 2.4 mg , starting at 4mg of reta should be fine, but if sema has been stopped for a while, then starting at 2mg would be safer, reta does have some different side effects to sema like more increased heart rate and skin sensitivity. But has less nausea and vomiting than sema.

The other thing to consider is the type 2 diabetes. GLP drugs rarely cause hypoglycaemia on their own, but once you start combining it with other diabetes drugs, it is more likely, so careful glucose monitoring is needed with starting it and with dose increases. Unfortunately diabetes patients consistently lose less weight than non diabetics, just to keep expectations realistic , so maybe average of 15 - 20 % rather than 29% for non diabetics, and the response to semaglutide was actually pretty good considering it is about 15-18% for non diabetics, and 20/146 is 13.8%.

Doing the standard 2mg start and 2mg increases every 4 weeks is likely to be fine, the fact that 2.4 of sema was tolerated means it is very unlikely that 12mg of reta would have worse side effects.

I also have some pretty unpleasant 10 year heart attack risk numbers, even with 80 kilos of weight loss. Reducing those risks is not just weight , good blood glucose control, reta will help there, but also making sure blood pressure and lipids are optimally treated, can reduce those risks a lot , and at least by a factor of 2.

If I had to guess he is going to lose some weight , but not likely to be more than 15-20% on reta. Even if this is a long way from perfect it can dramatically change health risks and is worth trying hard to preserve it. By staying on it and not stopping like was done with the sema, even if the results are a bit disappointing. Once he gets to a real plateau in a year or so, adding in cagri or eloralintide might be an option. At least with grey reta the price is not much of an issue compared with the legit versions. And at that level of overall health risk, the risks of grey peptides or combination therapies are likely to be much lower than the untreated obesity.

Thank you for detailed information.

He is not totally unresponsive to sema. But the progress is too small to be mentioned about and reaches the plateaus too fast. Losing 7-8 kgs takes about 10 weeks and then reaches the plateau. Stays pinning 2 more months without any changes and doctor advises to stop for a month and then start back. But during that month gains the same weight or more back.

I will let him start at 2mg and titrate 2mgs every 4 weeks until we find his sweet spot. Adding Cagri or Elarolintide is a far step at the moment. But I will keep it in mind until we get there.

As far as I know, he is checking his blood sugar every day. According to changes, I can ask further advice, if you don't mind?

 

[skaylife]

At 146 kg I still wouldn't start higher just because of body weight. I would start low and up the dose normally every 2-4 weeks. With Reta, tolerance is usually the limiting factor, not weight

Also if Ozempic stopped working, I wouldn't read too much into that. Plenty of people plateau on Sema and still respond very well to Tirz or Reta

The biggest mistake I see is people rushing the escalation because they want to get to the "effective" doses as fast as possible. I would rather take an extra few weeks and stay on the drug than push too hard and end up dealing with side effects. Most people who run into trouble do so because they increase too fast, not because they started too low

Sorry for my short response this morning. I had to start working and it was just before I left home. Thanks for your advice mate. He has a light response to sema. But not worth to talk about.

I agree and see also people around me beginning with rush and ending with regret. Saw them losing so many weight in a short time at high dosages with side effects like vomiting , nauseating..... I will support him through his journey and won't let hurry. He can get angry with me. But I am not scared. I can run faster 🤣 😉