Using GLP-1 Medications Smarter Versus Longer
There is rebound weight gain upon discontinuation of GLP-1 medications. This is the reality of the data. So when I hear about the widespread use of the medication, and the fact that many patients who start a GLP-1 medication discontinue use after 1-2 years, we need to have this conversation about not if but when you stop the GLP-1 medication. According to several studies, the discontinuation rate is approximately 50% at one year and 75% at two years. People stop for a lot of reasons, side effects and cost being the two main reasons. I think most people do not wish to be on chronic medication- especially an injectable one. The efficacy however is tempting. Many people see others around them losing weight with great success- and do not get me started on the social media before and after posts. These medications DO WORK for weight loss……..when you are taking them.
What happens though when you stop taking them?
According to a large meta-analysis study published this year in the British Medical Journal, most people regain weight lost upon discontinuing GLP-1 medication. Across 37 studies and 9,341 patients, weight was regained at an average rate of 0.4 kg monthly. This was actually faster than the weight lost at 0.3 kg monthly compared to the control arm. The control arm was non-pharmacological weight loss measures – basically lifestyle interventions. Even more compelling, all cardiometabolic improvements were extrapolated to be lost at 1.4 years post discontinuation of pharmaceutical medication.
In another metaanalysis published in the Lancet, at one year post stopping of GLP-1 medication, 60% of the weight lost was regained. The good news? The weight gain was extrapolated and plateaued at 75% which put the net loss still below starting point. That being said, only weight loss was measured and so really we do not know if body composition was improved at the end. Ultimately if percent lean body mass went down and fat mass was regained during and after cessation of GLP-1 use then the individual would actually be worse off from a cardiometabolic standpoint.
We also know from a recent JAMA article that many people do stop GLP-1 medication use typically after 1-2 years. In fact, 64% of patients without the diagnosis of Type 2 Diabetes stopped the medication within one year. The reason for stopping most cited was cost.
Maybe we need to use GLP-1 medications smarter instead of longer?
If the truth is most people using GLP-1 medications for weight loss will stop them at some point, maybe we need to be thinking about them in a different way and using them smarter. If you look at Obesity Medicine Guidelines, the recommendation is to stay on the medications indefinitely. But this is not practical or feasible for the majority of patients. Therefore we need to take an approach of using the medication to change the underlying pathophysiology to help with long term success. We must have the end game in mind at the start of pharmacological treatment for the majority of patients.
The initial weight regained.
The initial weeks after stopping the GLP-1 medication is a gradual increase in hunger and food seeking behavior. When we use these medications, because they are long acting analogs of the naturally occurring satiation hormone, our body becomes used to higher levels of this hormone. We have something called homeostasis – which is a checks and balances system in our body. When we stop taking this, our body rebounds and it takes time for that system to calibrate without the medication. The result of this recalibration is a voracious appetite while our body gets over the withdrawal. If we know this change is coming, first off we can intervene. We can also all along during use of GLP-1 use strategies that improve satiety by learning how to eat to trigger satiety.
We also can avoid pushing the dose if we are losing at a steady pace. I know we are all inpatient. We live in a fast paced immediate gratification world. The body is not like that when it comes to weight. If weight is being lost at a reasonable pace of 0.5-1 lb per week, I would suggest keeping the doses on the lower side with the end game in mind. The higher those, the higher the pharmaceutical appetite suppression and the greater the rebound hunger.
Gradually weaning the medication and using a maintenance dose for a period of time makes a lot of biological sense when it comes to these medications.
Long-term Metabolic Shifts
The insulin-carbohydrate model of obesity suggests that insulin resistance, blood glucose dysregulation and a feed forward cycle of inflammation is behind the pathophysiology of obesity. Therefore using GLP-1 medications makes a lot of sense to reverse the underlying pathophysiology. These medications stabilize blood sugar by initially increasing insulin production and ultimately suppress appetite so that a negative calorie balance can be sustained over the long term. This would then result in less insulin resistance over time and improvement of energy metabolism. If upon discontinuing the medication, there is a surplus of caloric intake particularly of foods that drive up blood glucose, overtime the benefits of the weight reduction will have been lost from a cardiometabolic standpoint. In fact, another study showed that waist circumference increased upon discontinuation of GLP-1 medications. The thinking here is that an increase in “belly fat” or waist circumference is associated with risk of chronic disease such as Diabetes Type 2, Cardiovascular Disease and Metabolic Liver Disease. These changes occur 8-12 weeks after stopping the medications. This suggests that metabolically there is not just a rebound of weight but a rebound of metabolic changes which are tied to blood glucose and insulin metabolism. There is much that can be done for this in anticipation with diet and lifestyle to stabilize blood glucose. In addition there are pharmaceutical and even nutraceutical stepdown therapies that work on similar targets mechanistically that could be of use in the withdrawal of GLP-1 support.
Safeguarding your metabolic rate
If we are seeing loss of lean body mass and not loss of fat mass then we likely will be in place of reduced basal metabolic rate upon discontinuation of the medication. Now if there is a lot of weight to lose and total body mass is high, there is an initial expected decrease in lean body mass and corresponding basal metabolic rate. However if overtime we are not seeing loss of fat mass and a stabilization of loss of lean body mass, this is a set up for regaining the weight. We have long known that exercise is a better weight loss maintenance strategy than an actual weight loss strategy. The phrase is “you can’t outrun the fork” and the data suggests this is true. But when it comes to body composition changes, there is where exercise can safeguard your metabolic rate and prevent the loss of muscle. In addition, the quality of the food you eat and prioritizing protein can also be key while using GLP-1 medications with the endgame in mind. Using medication to build these habits and improve body composition will help increase the likelihood of success if you do stop your medication.
Minding your microbiome
Patients who have success using GLP-1 medication in a way have suffered from a broken satiety switch. When the food hits the small intestines and natural GLP-1 hormone is produced, it sends a whole set of signals to the pancreas, liver and the brain to prepare for the incoming calories and to signal “stop eating”. The quality of the microbiome and the gut bacteria have an influence on this. Working on this during the treatment period is biologically plausible in the functional medicine model and again, another area of intervention to create long term success.
A Reset of Daily Habits
At the end of the day, what we need is a complete shift in our thinking and our habits around food. The medications, while taking them make it a bit easier to make the food choices that nourish our body. We need to expand our thinking while using the medications, connecting with why we want to improve our health and completely shifting how we live and our daily habits. It is possible to lose weight, shift body composition and improve health for the long term with the use of GLP-1 medications but you need to always have the final destination in mind through the journey.
References:
- West S, Scragg J, Aveyard P, Oke JL, Willis L, Haffner SJP, Knight H, Wang D, Morrow S, Heath L, Jebb SA, Koutoukidis DA. Weight regain after cessation of medication for weight management: systematic review and meta-analysis. BMJ. 2026 Jan 7;392
- Trajectory of weight regain after cessation of GLP-1 receptor agonists: a systematic review and nonlinear meta-regression
Budini, Brajan et al.
eClinicalMedicine, Volume 0, Issue 0, 103796 - Rodriguez PJ, Zhang V, Gratzl S, et al. Discontinuation and Reinitiation of Dual-Labeled GLP-1 Receptor Agonists Among US Adults With Overweight or Obesity. JAMA Netw Open. 2025;8(1):e2457349. doi:10.1001/jamanetworkopen.2024.57349
- Tzang CC, Wu PH, Luo CA, Chen ZT, Lee YT, Huang ES, Kang YF, Lin WC, Tzang BS, Hsu TC. Metabolic rebound after GLP-1 receptor agonist discontinuation: a systematic review and meta-analysis. EClinicalMedicine. 2025 Nov 28;90:103680.
