ForumDosing & Titration

Start dose Reta

12 replies6 peopleJun 9, 2026☆ Follow
Summary

what starting dose of retatrutide makes sense for someone at 146 kg with type 2 diabetes who has stopped responding to high-dose semaglutide

Participants recommend beginning at 1-2 mg weekly regardless of body weight or prior GLP-1 experience, then increasing by 1-2 mg every 2-4 weeks while watching tolerance. Several note that retatrutide can still produce good glucose and weight results even after semaglutide plateaus, though diabetics tend to lose less than non-diabetics. Slow titration is repeatedly stressed to avoid side effects that cause people to quit.

What this discussion establishesWhere people disagree

whether meaningful glucagon effects begin only near 8 mg or are already visible at 1-4 mg

Still open

how far to titrate before adding another agent such as cagrilintide

Nothing here is advice.

12 replies · 6 people
SlowBramble67archiveopening postJun 9

A friend of mine is 146 kg and has used the highest dose of Ozempic for years. He only lost about 20 kg at most and has now regained it; the medication no longer works. He wants to try retatrutide and asked about a starting dose. I tried it myself for a few weeks but quit after three days of bad diarrhea, so I have no real experience to offer. I know the usual schedule but have never been that heavy and do not know what dose would suit him. He also has type 2 diabetes. Any suggestions would help.

GreyAlder39archiveJun 9

The glucagon part of retatrutide really shows up at 8 mg per week in the studies, and that matters most for diabetes control. I began at 2.5 mg to check tolerance, then worked up to 10 mg weekly. My blood sugar now stays under 100 mg/dl even after dinner on a CGM, and it projects an HbA1c of 6.5 percent; it was 10.5 percent in February on tirzepatide. My BMI dropped from 31-32 to 27-28.

GreyAlder39archiveJun 9

Same situation here, just slightly lower at the pharmacy that adds no markup. I switched to the unregulated source and have no regrets.

AmberCinder46archiveJun 9

I started my sister on it after she had been on oral semaglutide. We began at 1 mg for four weeks, then stayed there another two because she responded well, and moved to 1.5 mg. After four months she is still at 2 mg and will probably remain there until she reaches her goal. After that I would likely move her to tirzepatide or cagrisema at a low dose for maintenance. Start low, 1 to 2 mg at most for a couple of weeks, then raise by 1 mg at a time. Tirzepatide is still the strongest option for pure weight loss in my view.

WarmCompass44archiveJun 9

Begin at 0.5 mg no matter what prior GLP-1 experience he has. Do that for one week, then add 0.5 mg each week until he finds a comfortable level or reaches 4 mg. Hold at 4 mg for several weeks before going higher.

RustSignal22archiveJun 9
↳ replying to @GreyAlder39

I am not convinced the glucagon effect only matters at 8 mg. Liver-fat reduction was already 51 percent at 1 mg and 59 percent at 4 mg after 48 weeks, with the largest further drop between 4 and 8 mg. The data show a clear effect well before 8 mg. Improved glucose numbers are also not proof of glucagon activity, since glucagon alone raises blood sugar; the HbA1c drop is more likely from the combined GLP-1 and GIP effects plus weight loss and better insulin sensitivity.

RustSignal22archiveJun 9

Even at 146 kg I would not start higher simply because of size. Begin low and increase every two to four weeks as usual. With retatrutide, tolerance is the real limit, not body weight. If semaglutide stopped working, that does not mean much; many people plateau on it yet respond well to the newer drugs. The main error I see is rushing the dose increases to reach the higher levels quickly. Taking a few extra weeks is better than pushing too fast and ending up with side effects that force a stop.

SlowBramble67archiveJun 10
↳ replying to @AmberCinder46

Thanks. I also responded better to tirzepatide than to retatrutide. My short trial of the latter ended with side effects, while 5 mg of tirzepatide got me to goal in eight months without much titration. Retatrutide was his choice, so I can mention tirzepatide again but he has a way of rationalizing that he does not overeat and blames cortisol instead. He does not really hear it when I point out that eating the wrong foods without burning calories is what drives the gain. We will see how it goes.

SlowBramble67archiveJun 10
↳ replying to @RustSignal22

I was not planning to jump from 4 mg straight to 8 mg anyway. I would go to 6 mg instead. Four to eight is a big increase.

GreyAlder39archiveJun 10
↳ replying to @RustSignal22

I did not claim there is a sharp threshold; that was your reading. The interesting part of retatrutide is precisely that the glucagon activity, even though it seems counterintuitive, helps when GLP-1 alone is not enough.

CopperSignal27archiveJun 10

The main practical difference with his starting weight is that he will probably need to go toward the top end of 12 mg over time. If he is still on semaglutide at 2.4 mg then 4 mg of retatrutide should be tolerable, but if he has been off it for a while then 2 mg is safer. Retatrutide can raise heart rate and cause skin sensitivity more than semaglutide, though it tends to cause less nausea and vomiting. Because he has type 2 diabetes, careful glucose monitoring is needed when starting or raising the dose, especially if he uses other diabetes medications. People with diabetes consistently lose less weight than non-diabetics, so realistic expectations are around 15-20 percent rather than the higher figures seen in non-diabetics. The standard approach of 2 mg to start with 2 mg increases every four weeks is reasonable.

SlowBramble67archiveJun 10
↳ replying to @CopperSignal27

Thank you for the detailed reply. He still has some response to semaglutide but it is very small and he hits plateaus quickly. Losing 7-8 kg takes about ten weeks, then nothing happens for another two months. The doctor then suggests stopping for a month, after which he regains the same amount or more. I will have him start at 2 mg and raise by 2 mg every four weeks until we find his effective level. Adding another agent is something to consider later. He already checks his blood sugar daily, so I can ask more questions later if needed.

SlowBramble67archiveJun 10
↳ replying to @RustSignal22

Sorry the earlier reply was so short; I had to leave for work. Thanks again for the input. His response to semaglutide is modest at best. I agree that rushing the schedule often leads to problems, and I have seen people around me lose a lot quickly at high doses only to deal with vomiting and nausea. I will help him go slowly and not let him hurry, even if he gets annoyed with me. I can always outrun him anyway.

Related discussions

Add your experience

If you have tried it, this topic is still open. Sign in to reply — it takes a minute.