Mid-way through year four here, but tirzepatide for the first 11 months only. Moved onto other options (maybe you don’t acknowledge that people do this, and that’s fine) that seem to be ridiculously effective at lower doses for 2-1/2 years now. So it’s possible that the next generation of GLPs will be the answer - and this space is evolving at a ridiculously rapid rate. Seems like a rollercoaster that we’re stuck on, for sure, but having lost 115lbs, I know what you’re talking about. I don’t want go back to where I was before.
I certainly hope you’re right and the next generation is the answer. I’m really glad to hear you’re having amazing results. Hopefully, I’ll get to be right behind you :)
I’ve lost 90 pounds and am happy at this weight. Began July 2024. If the meds ever stop working, I do not know what I will do. I like having good bloodwork, good mobility and the ability to easily buy clothes that fit.
I totally understand the fear. I think it’s less that they stopped working and more that for many people they feel less effective because of metabolic adaptation. The good news is there are a couple more about to get approved and coming out. It seems like that is at least a temporary solution.
Fascinating and much appreciated substack - I just passed the 2 year mark and just before that reached the lowest weight and now it is up 1 to 3 pounds then back down I go but not to the lowest level. It really seems like it is an adaptation the body is making to the medication that gets obscured when folks increase the dosage. I am at 11.25 mg of tirzepetide. I track my food most of the time but after a lifetime of tracking - I am dang tired of it. I have a cookie or 3 every once in a while and ice cream but my eating habits have changed dramatically with the elimination of the food noise but the cravings are back at a low level. I exercise and strength train more than I ever have which feels good mentally and physically but I got to admit the focus on food and eating enough protein, fiber and hydration is a part time job that occupies too much of my day. I shall look forward to your part 2. I never thought of obesity as a disease but I have changed my mind in the GLP-1 journey. I have 18 more pounds to lose but the good news is I still am losing fat and gaining muscle so body size going down but seems like the cortisol belly is changing very little - doesn’t help that at 76 a full hysterectomy and radiation 4 years ago wiped out my estrogen.
"'I felt like Neo in the Matrix, watching the food bullets drop' — then the white-knuckling coming back in year three. I've watched that arc from the other side of the counter, where we're the only clinicians who see patients monthly for years. The refill visits go from glowing to quiet, and the confession: the medicine 'stopped working.' Your phase four reframes what I say in those moments — the body defending its weight isn't the patient failing or the drug failing; it's the disease adapting. One change I've made: warning people at the START what years 3–5 can look like, so it never feels like betrayal. What do you wish someone had told you in year one?"
I wish someone had told there was no “goal weight” endgame. The same “listen to your body” approach that kept me sane in the beginning would be an ever shifting landscape due to body adaptation. Every body runs differently. Just finished year 4, grateful to be maintaining and still in remission.
Hi, Kim! I tried to meet you at OAC, but kept losing you in the crowd.
I started Trulicity in June 2022, then Mounjaro in Sept. 2023. I've been in remission from obesity since Feb 1, 2025, having lost 280 lbs. total. I'll be in year 5 starting in June 2027. (This is my 5th Halloween... without candy, thank goodness!)
When I went from Trulicity to Mounjaro, I started at 10mg., then to 12.5 a month later, then 15mg. a month after that. (Remember those old titration days?!) Yesterday was my 3rd anniversary on 15 mg. Mounjaro. I haven't met and talked to nearly the number of medical folks about these later years on the meds, so I am reading this with great interest. I just don't know people who have been on the meds this long! I feel like an outlier, so it's good to read your experiences. Thanks for writing about it.
I am blessed that I do not have Food Noise at all. I only recently realized I had hunger pangs in the last couple of months. My weight has stayed stable for 2 years in February... the average shift is 2.6 lbs. up or down. (Mind you, the scale has fluctuated between 124 and I37... the highs during hospitalizations and post-op experiences.) But generally, I am at a pretty stable 125-ish.
I had an RNY Gastric Bypass in 2001 and regained the 210 lbs. back within 5 years.
Anyway, you've definitely piqued my curiosity! I look forward to eventually meeting you!
The long term weight outcomes are (I think), what all of us interested in GLP-1s are wondering about. Even as a doctor, I am not naive enough to think science already has the answers - and those of us, like you and me, who are still on GLP-1s after years are literally building the data as we go. 10 years ago, I couldn’t have imagined a medication that would help me treat my obesity the way GLP-1s have. And so my hope is that 10 years from now, things will have moved along again, with proven effective long-term maintenance options. Work still has to go on in the background when it comes to what we eat and what we do, and yes, the body adapts. But perhaps, given long enough, it’s going to adapt right back to the pre-obesity physiology that makes all of this easier to manage. 🤞
Adapting to pre obesity physiology is the dream right?! They seem to think this is a from conception thing & just progresses. But ya know what?! I’ve interviewed the best of the best and even they don’t know for sure. It’s definitely the ocean with much left to explore. I guess what I’m trying to say is someone should frame this way for patients when they start instead of not saying anything because they think they don’t want to discourage them. And I think someone needs to connect the dots. In my opinion, they would not still be trying to make the mother of all obesity medication if the one we had solve the problem “forever”.
Been on OZ for 4 yrs now, to control my type 2D, A1C is under control and no real side effects, Each person is different and it’s not a “magic” fix for what got people into the place wherein they find themselves having to use it to drop and then maintain weight loss…
After being on terzepitde 15 for three years, I have begun to put weight back on again. No significant changes to diet and I do exercise quite frequently.
My blood sugar is maintaining, but it is very concerning to me.
In year 4. Normal weight now for 2 years. Definitely noticing that the urge to eat is stronger. Was beginning to question what is going on. Was even suspicious that the manufacturer was playing with the formula to save money. Lol. Your post makes more sense. Also still carrying around my old lap band so I feel you on the life long battle
Thanks for this. Midway through year 4. Maintaining at about 5-7 pounds over what I would like to weigh but working very hard to do that, counting calories, 26000 steps a day, cajoling myself. Thought this was a permanent solution to the disease but instead it is only part of a solution. So I am actually thinking of it as a tool.
Thank you for sharing this so honestly. I think one of the most important points here is that when hunger and food noise return, even while someone is still taking a GLP-1, we shouldn’t automatically assume they’ve lost discipline or stopped doing the right things. Obesity is a complex, chronic disease, and our understanding of long-term treatment is still evolving.
What fascinates me is the possibility that we’re only beginning to understand how metabolic adaptation, appetite regulation, insulin resistance, and changes in energy expenditure influence long-term responses to these medications. We need more research following patients beyond the first 5 years, especially those who experience renewed hunger or weight regain while still on treatment.
The goal shouldn’t be to blame patients when their response changes. It should be to understand why it changes and how treatment can be adapted. If obesity is a chronic disease, we need to study treatment as a long-term journey, not just measure success by how much weight someone loses in the first 4 years.
I appreciate your insights and I’m really learning from it. Oddly, the question that I have isn’t about the GLP 1s but the framework in which you describe obesity. When we look at childhood obesity, and how common it is now compared with where it was in the past—I’m curious about where this lands within your framework of the disease? I guess I’m asking where/how obesity begins?
This is so fascinating. I had a vertical sleeve gastrectomy in 2023 after a lifetime of struggling with my weight and developing T2 diabetes. I also have an immune disease that affects my kidneys. I was on the pink cloud of severe restriction and weight loss for 18 months, losing about 135 pounds. Until it just stopped. I started feeling hungry, but lost my appetite, but I could eat more, but nothing satisfied. Everything stalled, and then I started gaining weight. I was infuriated and felt betrayed by my body. I used to be able to eat a pint of Ben & Jerry's, and cake, and a burrito from Chipotle, and now I can't stomach ice cream at all, and I can eat four bites of a burrito, but I'm still gaining weight? I read a lot, mostly Andrew Jenkinson, MD, who has written a lot about metabolic adaptation, and I went back to the bariatric team who told me I needed to get a hobby and not focus so much on weight loss. I got a therapist, and a new nutritionist. Finally, I had a long conversation with my nephrologist who is recommending a GLP1 because of studies showing it can help slow progression of kidney disease. I saw my PCP, who described GLP1 as a "forever medication," and she wrote me a prescription for Zepbound. I feel very conflicted about taking this medication for "weight management," since my diabetes is well controlled despite my regain. But I am more frightened about losing kidney function than I am with other aspects of this medication and its pros/cons. I haven't started the shot yet, but I am looking forward to reading the rest of this series.
I think it’s mostly misinformation. They definitely come with risk. But in my experience, the risk of untreated obesity was much greater than the small chance of things going drastically wrong on GLP-1.
I think it’s actually more DISinformation. A lot of people claiming they’re harmful are in the wellness space — they make money from people’s diet and exercise.
Learning good habits is the issue. It doesn't matter what you eat. ONLY HOW MUCH & how Often. Exercise is NOT a weight loss solution-- it makes one hungrier. 80bites is what you should've learned. 80bites.com
"After all, why would the drug manufactures be creating so many other variations of this class of medicine if we all stuck with our habits, stayed thin and were cured?"
Because drug companies are making a ton of money on this........
Mid-way through year four here, but tirzepatide for the first 11 months only. Moved onto other options (maybe you don’t acknowledge that people do this, and that’s fine) that seem to be ridiculously effective at lower doses for 2-1/2 years now. So it’s possible that the next generation of GLPs will be the answer - and this space is evolving at a ridiculously rapid rate. Seems like a rollercoaster that we’re stuck on, for sure, but having lost 115lbs, I know what you’re talking about. I don’t want go back to where I was before.
I certainly hope you’re right and the next generation is the answer. I’m really glad to hear you’re having amazing results. Hopefully, I’ll get to be right behind you :)
I’ve lost 90 pounds and am happy at this weight. Began July 2024. If the meds ever stop working, I do not know what I will do. I like having good bloodwork, good mobility and the ability to easily buy clothes that fit.
I totally understand the fear. I think it’s less that they stopped working and more that for many people they feel less effective because of metabolic adaptation. The good news is there are a couple more about to get approved and coming out. It seems like that is at least a temporary solution.
Fascinating and much appreciated substack - I just passed the 2 year mark and just before that reached the lowest weight and now it is up 1 to 3 pounds then back down I go but not to the lowest level. It really seems like it is an adaptation the body is making to the medication that gets obscured when folks increase the dosage. I am at 11.25 mg of tirzepetide. I track my food most of the time but after a lifetime of tracking - I am dang tired of it. I have a cookie or 3 every once in a while and ice cream but my eating habits have changed dramatically with the elimination of the food noise but the cravings are back at a low level. I exercise and strength train more than I ever have which feels good mentally and physically but I got to admit the focus on food and eating enough protein, fiber and hydration is a part time job that occupies too much of my day. I shall look forward to your part 2. I never thought of obesity as a disease but I have changed my mind in the GLP-1 journey. I have 18 more pounds to lose but the good news is I still am losing fat and gaining muscle so body size going down but seems like the cortisol belly is changing very little - doesn’t help that at 76 a full hysterectomy and radiation 4 years ago wiped out my estrogen.
Thanks again for writing this all out.
"'I felt like Neo in the Matrix, watching the food bullets drop' — then the white-knuckling coming back in year three. I've watched that arc from the other side of the counter, where we're the only clinicians who see patients monthly for years. The refill visits go from glowing to quiet, and the confession: the medicine 'stopped working.' Your phase four reframes what I say in those moments — the body defending its weight isn't the patient failing or the drug failing; it's the disease adapting. One change I've made: warning people at the START what years 3–5 can look like, so it never feels like betrayal. What do you wish someone had told you in year one?"
I wish someone had told there was no “goal weight” endgame. The same “listen to your body” approach that kept me sane in the beginning would be an ever shifting landscape due to body adaptation. Every body runs differently. Just finished year 4, grateful to be maintaining and still in remission.
Hi, Kim! I tried to meet you at OAC, but kept losing you in the crowd.
I started Trulicity in June 2022, then Mounjaro in Sept. 2023. I've been in remission from obesity since Feb 1, 2025, having lost 280 lbs. total. I'll be in year 5 starting in June 2027. (This is my 5th Halloween... without candy, thank goodness!)
When I went from Trulicity to Mounjaro, I started at 10mg., then to 12.5 a month later, then 15mg. a month after that. (Remember those old titration days?!) Yesterday was my 3rd anniversary on 15 mg. Mounjaro. I haven't met and talked to nearly the number of medical folks about these later years on the meds, so I am reading this with great interest. I just don't know people who have been on the meds this long! I feel like an outlier, so it's good to read your experiences. Thanks for writing about it.
I am blessed that I do not have Food Noise at all. I only recently realized I had hunger pangs in the last couple of months. My weight has stayed stable for 2 years in February... the average shift is 2.6 lbs. up or down. (Mind you, the scale has fluctuated between 124 and I37... the highs during hospitalizations and post-op experiences.) But generally, I am at a pretty stable 125-ish.
I had an RNY Gastric Bypass in 2001 and regained the 210 lbs. back within 5 years.
Anyway, you've definitely piqued my curiosity! I look forward to eventually meeting you!
-Barb
The long term weight outcomes are (I think), what all of us interested in GLP-1s are wondering about. Even as a doctor, I am not naive enough to think science already has the answers - and those of us, like you and me, who are still on GLP-1s after years are literally building the data as we go. 10 years ago, I couldn’t have imagined a medication that would help me treat my obesity the way GLP-1s have. And so my hope is that 10 years from now, things will have moved along again, with proven effective long-term maintenance options. Work still has to go on in the background when it comes to what we eat and what we do, and yes, the body adapts. But perhaps, given long enough, it’s going to adapt right back to the pre-obesity physiology that makes all of this easier to manage. 🤞
Adapting to pre obesity physiology is the dream right?! They seem to think this is a from conception thing & just progresses. But ya know what?! I’ve interviewed the best of the best and even they don’t know for sure. It’s definitely the ocean with much left to explore. I guess what I’m trying to say is someone should frame this way for patients when they start instead of not saying anything because they think they don’t want to discourage them. And I think someone needs to connect the dots. In my opinion, they would not still be trying to make the mother of all obesity medication if the one we had solve the problem “forever”.
Been on OZ for 4 yrs now, to control my type 2D, A1C is under control and no real side effects, Each person is different and it’s not a “magic” fix for what got people into the place wherein they find themselves having to use it to drop and then maintain weight loss…
After being on terzepitde 15 for three years, I have begun to put weight back on again. No significant changes to diet and I do exercise quite frequently.
My blood sugar is maintaining, but it is very concerning to me.
THIS IS NOT ADVICE. I am wondering if weight training and adding myscle tissue can stabilize metabolism or is that wishful thinking?
In year 4. Normal weight now for 2 years. Definitely noticing that the urge to eat is stronger. Was beginning to question what is going on. Was even suspicious that the manufacturer was playing with the formula to save money. Lol. Your post makes more sense. Also still carrying around my old lap band so I feel you on the life long battle
Thanks for this. Midway through year 4. Maintaining at about 5-7 pounds over what I would like to weigh but working very hard to do that, counting calories, 26000 steps a day, cajoling myself. Thought this was a permanent solution to the disease but instead it is only part of a solution. So I am actually thinking of it as a tool.
Thank you for sharing this so honestly. I think one of the most important points here is that when hunger and food noise return, even while someone is still taking a GLP-1, we shouldn’t automatically assume they’ve lost discipline or stopped doing the right things. Obesity is a complex, chronic disease, and our understanding of long-term treatment is still evolving.
What fascinates me is the possibility that we’re only beginning to understand how metabolic adaptation, appetite regulation, insulin resistance, and changes in energy expenditure influence long-term responses to these medications. We need more research following patients beyond the first 5 years, especially those who experience renewed hunger or weight regain while still on treatment.
The goal shouldn’t be to blame patients when their response changes. It should be to understand why it changes and how treatment can be adapted. If obesity is a chronic disease, we need to study treatment as a long-term journey, not just measure success by how much weight someone loses in the first 4 years.
Yes! Exactly this! Thank you.
I appreciate your insights and I’m really learning from it. Oddly, the question that I have isn’t about the GLP 1s but the framework in which you describe obesity. When we look at childhood obesity, and how common it is now compared with where it was in the past—I’m curious about where this lands within your framework of the disease? I guess I’m asking where/how obesity begins?
This is so fascinating. I had a vertical sleeve gastrectomy in 2023 after a lifetime of struggling with my weight and developing T2 diabetes. I also have an immune disease that affects my kidneys. I was on the pink cloud of severe restriction and weight loss for 18 months, losing about 135 pounds. Until it just stopped. I started feeling hungry, but lost my appetite, but I could eat more, but nothing satisfied. Everything stalled, and then I started gaining weight. I was infuriated and felt betrayed by my body. I used to be able to eat a pint of Ben & Jerry's, and cake, and a burrito from Chipotle, and now I can't stomach ice cream at all, and I can eat four bites of a burrito, but I'm still gaining weight? I read a lot, mostly Andrew Jenkinson, MD, who has written a lot about metabolic adaptation, and I went back to the bariatric team who told me I needed to get a hobby and not focus so much on weight loss. I got a therapist, and a new nutritionist. Finally, I had a long conversation with my nephrologist who is recommending a GLP1 because of studies showing it can help slow progression of kidney disease. I saw my PCP, who described GLP1 as a "forever medication," and she wrote me a prescription for Zepbound. I feel very conflicted about taking this medication for "weight management," since my diabetes is well controlled despite my regain. But I am more frightened about losing kidney function than I am with other aspects of this medication and its pros/cons. I haven't started the shot yet, but I am looking forward to reading the rest of this series.
I am puzzled by those who are frightened by these meds. I’ve had nothing but good from them.
I think it’s mostly misinformation. They definitely come with risk. But in my experience, the risk of untreated obesity was much greater than the small chance of things going drastically wrong on GLP-1.
I think it’s actually more DISinformation. A lot of people claiming they’re harmful are in the wellness space — they make money from people’s diet and exercise.
Learning good habits is the issue. It doesn't matter what you eat. ONLY HOW MUCH & how Often. Exercise is NOT a weight loss solution-- it makes one hungrier. 80bites is what you should've learned. 80bites.com
80 bites cures obesity?
"After all, why would the drug manufactures be creating so many other variations of this class of medicine if we all stuck with our habits, stayed thin and were cured?"
Because drug companies are making a ton of money on this........