ForumResults & Progress

Sema non-responders, have you had better luck with tirz or reta?

5 replies6 peopleJun 22, 2026☆ Follow
Summary

Do people who see no results from semaglutide respond better to tirzepatide or retatrutide?

Several users report zero weight loss or appetite effects on sema despite dose increases, with only fatigue noted. Switching to retatrutide produced clear appetite changes and steady loss for some who had stalled on sema, while others saw only mild appetite shifts and no scale movement on both sema and tirz. Genetic differences in GLP-1 pathways are suggested as a possible cause, and trying reta or amylin agonists is viewed as a reasonable next step even if odds are lower than average.

What this discussion establishesWhere people disagree

Some found reta effective after sema failure while others saw little benefit from either sema or tirz.

Still open

Whether non-responders to GLP-1 drugs will reliably respond to dual or triple agonists.

Nothing here is advice.

5 replies · 6 people
PatientTimber93archiveopening postJun 22

My spouse tried semaglutide for six months, reaching a top dose of 1 mg. There was zero effect of any kind, no appetite control and no pounds lost, only tiredness. Would switching to tirzepatide or retatrutide give a better shot at results? Anyone seen cases like this with people who show no response?

CopperSignal27archiveJun 22

So far no studies address this situation at all. Going straight to reta makes sense because if GLP-1 alone does little, adding GIP and glucagon might change things, or trying an amylin drug like cagri could work through a different route. Variants in the GLP-1 receptor or its signaling pathways likely explain why some people get almost no weight loss. Odds of also responding poorly to tirz or reta are probably higher than normal, though still worth testing for a couple of months. I stayed on low-dose ozempic for a year with no scale movement, just constant tiredness and mild nausea, though appetite was somewhat lower.

WarmWillow50archiveJun 25

Response can depend on several factors, including whether someone has type 2 diabetes or takes meds like gabapentin. Plenty of people moved from sema to tirz or reta and saw stronger effects. It seems worth testing one of those before giving up on the whole group of GLP drugs.

CopperAlder51archiveJun 25

I stayed on sema nearly a full year. The first two months brought ten pounds off, then progress stopped completely. Appetite suppression stayed weak and I felt awful the whole time. Moving to reta changed everything.

GreyWillow57archiveJul 5
↳ replying to @PatientTimber93 (opening post)

I can share what happened in my case. After three months of sema titrated by my doctor I had some appetite drop but stayed fatigued and dropped no weight, so it was stopped. Starting the lowest dose of Mounjaro gave slight nausea yet some loss right away, probably water, plus much less interest in fried food and smaller portions. A week later I began reta, now at 2 mg after starting at 1 mg. Four weeks in the scale is down seven pounds while I also lift and use creatine plus whey. Face looks slimmer and shirts fit better even if changes are gradual.

KeenKettle50archiveJul 5
↳ replying to @CopperSignal27

Same experience here. Ozempic and tirzepatide each gave only a small reduction in hunger with no actual weight coming off.

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