adverse effects of stopping GLP medications, as evidence suggests risks are associated with Weight cycling

[MsGizmo]

I hate to say it... I agree. After being on sema, and stacking others, I had to stop for 8 weeks as I had scheduled surgeries.. one that got pushed back two weeks. I had stopped a few other times but for only a week or two due to surgeries and colonoscopies.

I was at my absolute lowest since I started this peptide journey. The noise came back full force. I was ravenous. I ate like I had not in 4 years. The holidays and having junk in the house has not helped. Thankfully I have only gained about 7 lbs but... I absolutely hate this. I "thought" I had my shit in check. I eat healthy, walk a lot, do some strength training.. but I don't deprive myself when I want something sweet.. I just eat a "normal" portion. Now? Once I start eating junk I just want more...

I have restarted what I was taking but low and slow. I do not want to get sick because I am eating like an asshole. I still think they are the answer but I am convinced I will be pinning something until the day I die...

When I took my very first dose I was already planning on taking it long term, even without a full fledged plan on how to pay for it beyond the first year. Fortunately I learned about the grey market after the first 2 months. I have no intention of ever stopping. I do have a medical procedure scheduled in February and I will most likely have to take a 2 week break .. I am not looking forward to it.

 

[Laxfinity]

When I took my very first dose I was already planning on taking it long term, even without a full fledged plan on how to pay for it beyond the first year. Fortunately I learned about the grey market after the first 2 months. I have no intention of ever stopping. I do have a medical procedure scheduled in February and I will most likely have to take a 2 week break .. I am not looking forward to it.

Two weeks wasn't bad. I have done that a few times. You will still have some of your dosage in your body. My situation was not by choice.. trust me. Back a few years ago everyone spoke about "resets".. stopping a few months and restarting to stop a stall. I never subscribed to that theory.

 

[cookieguggleman]

I have always approached GLP-1s as a treatment, and not a cure. I intend to stay on some version of them for life. That might explain my completely irrational desire to hoard multiple years' worth. I'm never going off. I'm never going back. I just can't.

But their efficacy fades with time. So staying on them for life won’t necessarily work.

 

[Grogu]

But their efficacy fades with time. So staying on them for life won’t necessarily work.

I'm not sure if there is enough data to support the statement that the efficacy of glp-1 medications fades with time. The medications just haven't been used that long for weight management.

But this article from earlier this year reports long-term usage of tirzepatide and the results suggest that at least at 3 years that study participants were able to maintain their weight loss while staying on the dosage of tirzepatide assigned at randomization.

Tirzepatide for Obesity Treatment and Diabetes Prevention - PubMed

Three years of treatment with tirzepatide in persons with obesity and prediabetes resulted in substantial and sustained weight reduction and a markedly lower risk of progression to type 2 diabetes than that with placebo. (Funded by Eli Lilly; SURMOUNT-1 ClinicalTrials.gov number, NCT04184622.).

pubmed.ncbi.nlm.nih.gov

The increase at week 176 through 193 is off-treatment.

The flatening of the weight loss line at week 85 and the line staying flat, suggests to me that weight loss is pretty durable while on treatment. So, at least at 3 years there is no loss of efficacy. The flat line is beautiful to me and really exciting.

 

[cookieguggleman]

I'm not sure if there is enough data to support the statement that the efficacy of glp-1 medications fades with time. The medications just haven't been used that long for weight management.

But this article from earlier this year reports long-term usage of tirzepatide and the results suggest that at least at 3 years that study participants were able to maintain their weight loss while staying on the dosage of tirzepatide assigned at randomization.

Tirzepatide for Obesity Treatment and Diabetes Prevention - PubMed

Three years of treatment with tirzepatide in persons with obesity and prediabetes resulted in substantial and sustained weight reduction and a markedly lower risk of progression to type 2 diabetes than that with placebo. (Funded by Eli Lilly; SURMOUNT-1 ClinicalTrials.gov number, NCT04184622.).

pubmed.ncbi.nlm.nih.gov

The increase at week 176 through 193 is off-treatment.

The flatening of the weight loss line at week 85 and the line staying flat, suggests to me that weight loss is pretty durable while on treatment. So, at least at 3 years there is no loss of efficacy. The flat line is beautiful to me and really exciting.

View attachment 12213

Three years isn’t long term at all.

If the efficacy doesn’t wear off, then why do we have to increase dosage?

 

[Grogu]

Three years isn’t long term at all.

If the efficacy doesn’t wear off, then why do we have to increase dosage?

I hear you—but given my own history of losing 100+ pounds several times and not keeping it off anywhere close to three years, holding steady at my current weight for that long would feel like a godsend. I’m not claiming we have lifetime data; I actually said we don’t have enough time-on-drug to make sweeping “long-term” declarations. What we can say is that the best evidence so far suggests weight loss can be durable while on treatment out to about three years, which is a meaningful real-world benchmark. And on dosing, increases don’t prove “wear-off”—a lot of that is titration to therapeutic levels plus individual variability. Many people at 5 mg simply aren’t at an effective dose yet, which is very different from the medication losing efficacy.

 

[MsGizmo]

Three years isn’t long term at all.

If the efficacy doesn’t wear off, then why do we have to increase dosage?

I think it has to do with continued weight loss. Like taking 2mg of substance x will get you down 50 pounds but you will need to increase your dose to lose another 10 pounds.

For example My husband is a diabetic at a healthy weight, we both took semaglutide. I lost weight but he didn't.

 

[Thistley]

This is my second new years on my 18 month GLP1 journey. I came off a months long stall with mounjaro. Went grey in 2025 and commenced Reta in September.

Three months on Reta, now at 7mg and I’ve dropped 14lbs. Hardly melting away. That’s because the smaller doses of Reta didn’t work for me and 6mg is where weight loss started happening again. As many here suggested and I am delighted with it.

Until…. I hit another stall. This is my third week of staying the same and I increased to 7mg. I was not prepared for how I’d feel hitting a 3 week stall not knowing when or if it will ending, how much that’s challenged my feelings about the journey ahead, and while I know it’s the long game I still have 50lbs to lose. It hits me right in the hope. Hard. Because even then I will still be classed by BMI as obese.

In this stall… I know something is up in my body, I feel it. I have pcos, a metabolic disorder, and I know from the appearance of odd symptoms something is out of whack in my hormones (erm hello is that you perimenopause ?). Make sense it would affect all my systems. But it will pass.

Long way of saying …. I think I know I will be on some form of this long term and I feel good and reassured about my 2 years of peptide freezer supplies.

I knew I would probably have to keep taking it to feel normal and keep the weight stable: I have accepted now there is something wrong with me that cannot be cured and will worsen again without helping myself using this treatment, combined with diet and ongoing exercise for health and self care.

Sending love to @Laxfinity because as bad as I’m feeling, I’d be really depressed if I put 7lbs back on over the festive when it took me 7 dang months to lose it. Reading your story I thank you for sharing it because I feel for you! You will drop it again. Onwards we go!

 

[mlke6]

Three years isn’t long term at all.

If the efficacy doesn’t wear off, then why do we have to increase dosage?

seems like you only have to increase when you hit certain weight "stalls" not because it no longer works anymore. At least that's what I experienced. Like If I wanted to stay at 200 lbs I would have stayed on a smaller dose of Tirz. I kept going Until I Hit around 155 to 160. I haven't tried it out but I bet if i went higher I would lose more. Even though I still feel over 200lbs at times looking in the mirror is a reality check that I'm at a good size. Kinda do want to try it though but I feel that might be a dark road...

 

[Laxfinity]

This is my second new years on my 18 month GLP1 journey. I came off a months long stall with mounjaro. Went grey in 2025 and commenced Reta in September.

Three months on Reta, now at 7mg and I’ve dropped 14lbs. Hardly melting away. That’s because the smaller doses of Reta didn’t work for me and 6mg is where weight loss started happening again. As many here suggested and I am delighted with it.

Until…. I hit another stall. This is my third week of staying the same and I increased to 7mg. I was not prepared for how I’d feel hitting a 3 week stall not knowing when or if it will ending, how much that’s challenged my feelings about the journey ahead, and while I know it’s the long game I still have 50lbs to lose. It hits me right in the hope. Hard. Because even then I will still be classed by BMI as obese.

In this stall… I know something is up in my body, I feel it. I have pcos, a metabolic disorder, and I know from the appearance of odd symptoms something is out of whack in my hormones (erm hello is that you perimenopause ?). Make sense it would affect all my systems. But it will pass.

Long way of saying …. I think I know I will be on some form of this long term and I feel good and reassured about my 2 years of peptide freezer supplies.

I knew I would probably have to keep taking it to feel normal and keep the weight stable: I have accepted now there is something wrong with me that cannot be cured and will worsen again without helping myself using this treatment, combined with diet and ongoing exercise for health and self care.

Sending love to @Laxfinity because as bad as I’m feeling, I’d be really depressed if I put 7lbs back on over the festive when it took me 7 dang months to lose it. Reading your story I thank you for sharing it because I feel for you! You will drop it again. Onwards we go!

Thank you.

What I didn't share is I had a BC scare. I had 7 biopsies and 5 lumpectomies over that time period. I chose to take a scheduled trip in between and got bumped for 2 weeks from when the lumpectomies were originally scheduled... hence why I had to go off for 8 weeks.

I am benign thankfully and I am so grateful. I could care less about the 7 lbs even though it had been screwing with my brain a bit. It was HOW I was eating again. Seriously WTF. I am back down a few pounds already... and I feel great emotionally and physically after a 4 month scare that put my brain and body places I haven't been before. Most important.

Please take away this... GET YOUR ANNUAL MAMMOGRAMS! Or at least ultrasounds or MRIs. I truly believe because I have always had dense breasts and am so diligent we caught everything early. I had a radial scar and ALH left, and (3) ADHs right... and I am grateful they are not there anymore.

Happy New Year to all.

 

[tncc_rn]

I hate to say it... I agree. After being on sema, and stacking others, I had to stop for 8 weeks as I had scheduled surgeries.. one that got pushed back two weeks. I had stopped a few other times but for only a week or two due to surgeries and colonoscopies.

I was at my absolute lowest since I started this peptide journey. The noise came back full force. I was ravenous. I ate like I had not in 4 years. The holidays and having junk in the house has not helped. Thankfully I have only gained about 7 lbs but... I absolutely hate this. I "thought" I had my shit in check. I eat healthy, walk a lot, do some strength training.. but I don't deprive myself when I want something sweet.. I just eat a "normal" portion. Now? Once I start eating junk I just want more...

I have restarted what I was taking but low and slow. I do not want to get sick because I am eating like an asshole. I still think they are the answer but I am convinced I will be pinning something until the day I die...

"GLPs are for life"..... Learn it, live it, LOVE it.

 

[tncc_rn]

This is my second new years on my 18 month GLP1 journey. I came off a months long stall with mounjaro. Went grey in 2025 and commenced Reta in September.

Three months on Reta, now at 7mg and I’ve dropped 14lbs. Hardly melting away. That’s because the smaller doses of Reta didn’t work for me and 6mg is where weight loss started happening again. As many here suggested and I am delighted with it.

Until…. I hit another stall. This is my third week of staying the same and I increased to 7mg. I was not prepared for how I’d feel hitting a 3 week stall not knowing when or if it will ending, how much that’s challenged my feelings about the journey ahead, and while I know it’s the long game I still have 50lbs to lose. It hits me right in the hope. Hard. Because even then I will still be classed by BMI as obese.

In this stall… I know something is up in my body, I feel it. I have pcos, a metabolic disorder, and I know from the appearance of odd symptoms something is out of whack in my hormones (erm hello is that you perimenopause ?). Make sense it would affect all my systems. But it will pass.

Long way of saying …. I think I know I will be on some form of this long term and I feel good and reassured about my 2 years of peptide freezer supplies.

I knew I would probably have to keep taking it to feel normal and keep the weight stable: I have accepted now there is something wrong with me that cannot be cured and will worsen again without helping myself using this treatment, combined with diet and ongoing exercise for health and self care.

Sending love to @Laxfinity because as bad as I’m feeling, I’d be really depressed if I put 7lbs back on over the festive when it took me 7 dang months to lose it. Reading your story I thank you for sharing it because I feel for you! You will drop it again. Onwards we go!

I notice users of Reta usually also include stories of exercise along with the Reta. Triz just seems to work just by taking it. Also, this is my 3rd go around with Reta. I never got above 4mg a week before I gave up and went back in Triz. This time I will go to 12mg before I give up on it. If it doesn't work at 12mg/week, I will know it's just not for me.