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Anyone who’s struggled with their weight—or who sees patients who do—knows that the long-term outlook isn’t exactly encouraging. As difficult as it can be for some people to lose weight, many can attest that keeping it off permanently is the tougher battle. The norm is to regain weight; maintaining a lower weight long-term is the exception. A recent BMJ editorial didn’t mince words about this. Noting that obesity is difficult to treat and manage, the author wrote, “…weight regain is almost inevitable for most people who initially lose weight.”
Medications for weight loss aren’t new, and they have even been called “highly effective,” and it’s said that they’ve “transformed the treatment of obesity.” However, the very same paper that included those phrases also noted that cessation of weight management medications (WMM) “is followed by rapid weight regain and reversal of beneficial effects on cardiometabolic markers.” (Emphasis added.) Not exactly a rousing endorsement for the capacity of medications to “transform the treatment of obesity.”
Statistics may be a bit grim, but there’s room for optimism. A systematic review and meta-analysis published recently in the BMJ compared 37 trials and cohort studies encompassing just over 9300 participants in order to assess the rate of regain after cessation of weight management medications (WMM) and compare that to the rate of regain reported after cessation of behavioral weight management programs (BWMP) involving support for changes to diet and physical activity. The medications in the studies analyzed included semaglutide and tirzepatide as well as older medications, such as liraglutide, exenatide, orlistat, phentermine, phentermine plus topiramate, naltrexone plus bupropion, sibutramine, and others.
The average treatment duration was 39 weeks (range 11–176 weeks) with an average follow-up of 32 weeks (4–104 weeks). The overall average monthly rate of weight regain after stopping either method (medication or behavioral strategies) was 0.4 kg. The rate of regain was higher after stopping WMM than after stopping BWMP (by 0.3 kg monthly), independent of initial weight loss. It was predicted that subjects would return to their baseline weight after 1.7 years, and the improvements in cardiometabolic markers that occurred during the weight loss (e.g., HbA1c, fasting glucose, total cholesterol, triglycerides, and blood pressure) were projected to return to baseline within a year and a half after the cessation of WMMs.
One interpretation of those findings is that people should simply stay on the medication. If weight regain and reversal of beneficial health improvements occur after stopping a drug, then logic suggests that the drug should be continued. However, as noted in the meta-analysis, “Real world observations estimate that around 50% of people with obesity discontinue WMMs within 12 months.” Medications may be stopped due to intolerable side-effects, financial factors, changes in access or insurance coverage, or because someone feels the medication is no longer effective for them. So, for the fifty percent of people who stop WMM—and for those for whom they’re not an option in the first place or who simply prefer to avoid them—is there a different approach that could be effective over the longer term, or should they make peace with being in a larger body?
Two studies published within the past two years show that a very low-carb diet accompanied by professional support can result in similar maintenance of weight loss over time among people who discontinue WMM and those who keep taking them.
The first, published in 2024, showed that among subjects with type 2 diabetes and obesity, weight regain was minimal one year after stopping GLP-1 receptor agonist medications (GLP-1RA), and it was not significantly different compared to a slight regain among those who were still taking the medications. Additionally, HbA1c increased after discontinuing the medications, but for more than half of the subjects, it still remained below the cutoff for type 2 diabetes one year out. Moreover, approximately 20 percent of both cohorts—those who remained on medication and those who discontinued—maintained a normal HbA1c (< 5.7%) one year out.
More than 70% of patients in each of the matched cohorts maintained at least 5% body weight loss 12 months. More than 50% maintained at least at 10% loss of body weight. More than 25% maintained at least a 15% loss, and 14% maintained at least a 20% loss of body weight after one year—again, this was among patients who continued taking weight loss medication and those who stopped the meds.
Both cohorts of patients were enrolled in a program that recommends a very-low-carb diet (less than 30 g per day), with protein intake around 1.5 g/kg of reference body weight, and fat intake titrated to achieve satiety while enabling weight loss. The program also calls for regular reporting of blood glucose and ketone levels (beta-hydroxybutyrate), with follow-ups and check-ins with a clinician or health coach “individualized on the basis of patient outreach and health need and can be as often as daily.”
In a more recent study that also involved a weight loss program with coaching and real-time biofeedback, mean weight loss at one year was 43 pounds (19.5 kg), corresponding to 15.5% total body weight loss, with concomitant deprescription of 96 medications(mostly for type 2 diabetes, hypertension, and acid reflux). Of the medications deprescribed, four were GLP-1RA (3 semaglutide and 1 dulaglutide). Mean time to last follow up after beginning taper and complete deprescription was 487 days and 270 days, respectively. After complete cessation of GLP-1RAs, two subjects continued to lose weight and two experienced only slight regain. Overall, total weight loss was comparable in patients with and without use of GLP-1RA medications.
This intervention also called for a low-carb diet in combination with health coaching, group meetings and webinars, plus real-time biofeedback at least temporarily (via a continuous glucose monitor or regular glucometer) and remote monitoring of blood pressure, body composition, blood glucose and ketones.
Both of these studies indicate that significant weight regain is not inevitable after discontinuing WMM. People can continue losing or experience only minimal regain, but ongoing support appears to be a key factor. This is a missing piece for many who attempt weight loss on their own, and it may be especially relevant for those who use medication to assist their weight loss but for whom there’s no system in place for regular check-ins or support after cessation of medication. The 2024 study noted, “Body weight did not rise in the 12 months following deprescription of GLP-1 therapy when patients continued carbohydrate restricted nutrition therapy supported via telemedicine in a continuous remote care model.” (Emphasis added.)
Weight loss is not a “set it and forget it” endeavor. For some people—perhaps the majority—ongoing support from a clinician and/or a health coach or supportive community may be a pivotal factor in long-term success, whether or not weight loss medications play a role in the initial loss.
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