Weight Loss Medication: Why Do Results Disappear When Treatment Ends?

Researchers analyzed several studies to understand what happens when people using weight-loss medications stop their treatment. They found that, on average, weight gain begins about two months after stopping and continues to increase in the following months, reaching up to 2.5 kg in five months. This shows that maintaining results requires long-term monitoring and strategies, even after stopping the medication.

Obesity is currently one of the greatest challenges for global public health. In 2020, an estimated 2.2 billion adults worldwide were overweight or obese, and this number is projected to rise to 3.3 billion by 2035.

This condition is not just a cosmetic issue: it is linked to a much higher risk of developing serious diseases, such as cardiovascular problems, type 2 diabetes, and several types of cancer. Therefore, controlling it is essential to prevent complications and improve quality of life and life expectancy.

Obesity treatment may involve behavioral and lifestyle changes, specific medications, and, in some cases, bariatric surgery. Currently, there are six medications approved for the treatment of obesity in adults: orlistat (Xenical), naltrexone-bupropion (Contrave, Mysimba), liraglutide (Saxenda, Victoza), semaglutide (Wegovy, Ozempic), tirzepatide (Mounjaro, Zepbound), and phentermine-topiramate (Qsymia).

Weight-loss medications work in different ways to help you lose weight. Orlistat (Xenical) works in the intestines, blocking some of the fat in food from being absorbed. The naltrexone-bupropion combination (Contrave, Mysimba) works in the brain, reducing food cravings and helping control binge eating.

Liraglutide (Saxenda, Victoza), semaglutide (Wegovy, Ozempic), and tirzepatide (Mounjaro, Zepbound) mimic natural hormones, such as GLP-1, that regulate appetite and metabolism, making you feel less hungry and feel fuller faster.

Phentermine-topiramate (Qsymia) combines two medications: one that reduces appetite and gives you more energy, and another that alters how the brain perceives food, helping you eat less.

Studies show that, when used for long periods, these medications can help with weight loss and improve obesity-related health problems. However, there is a significant challenge: many people regain weight when they stop taking these medications, which can reverse some of the benefits achieved.

The problem is that when these medications are stopped, the body tends to revert to its previous pattern, increasing hunger and promoting weight regain.

The study in question sought to better understand what happens to people's weight after stopping these medications. To do this, researchers at Peking University People's Hospital in China conducted a detailed analysis of previously conducted clinical studies.

They searched scientific databases and selected only clinical trials that compared people who used anti-obesity medications with groups who did not, following them during treatment and also after the medication was discontinued. They required that treatment last at least four weeks, and that follow-up after discontinuation also be at least four weeks. This made it possible to compare weight loss during medication use with what occurred in the weeks following its discontinuation.

The results showed that four weeks after stopping the medication, there was still some positive effect compared to the group that had never used it, but this difference was not significant.

Eight weeks after stopping, however, a clear and significant weight gain was observed, which continued to increase in the following weeks: an average of 1.5 kg after eight weeks, 1.76 kg after twelve weeks, and 2.5 kg after twenty weeks.

Weight and BMI recover after weight-loss treatment. BMI: body mass index

The most pronounced weight gain was observed in people who had used medications that mimic the GLP-1 hormone, such as liraglutide and semaglutide. Furthermore, people who lost more weight during treatment or who maintained lifestyle changes even after stopping the medication also experienced weight gain, although the weight return was slower.

The conclusion was that weight regain after stopping anti-obesity medications is common and can begin quickly, about two months after stopping, and continue for the following months.

This reinforces the need for long-term weight monitoring and maintenance strategies, as well as longer-term studies to understand the factors that influence this regain and how to prevent it.

READ MORE:

Trajectory of the body weight after drug discontinuation in the treatment of anti-obesity medications

Han Wu, Wenjia Yang, Tong Guo, Xiaoling Cai, and Linong Ji 

BMC Medicine, volume 23, Article number: 398 (2025) 

https://doi.org/10.1186/s12916-025-04200-0

Abstract: 

Globally, obesity has emerged as a significant public health concern, imposing detrimental impacts on human health. The purpose of our study was to explore the long-term effects of anti-obesity medications (AOMs) on body weight and to draw the trajectory of weight change after discontinuation of AOMs. PubMed, Medline, Embase, the Cochrane Center Register of Controlled Trials for Studies, and Clinicaltrials.gov were searched from the inception to March 2024. Randomized controlled trials of AOMs conducted in population for at least 4 weeks and followed for 4 or more weeks after discontinuation were included. Weight change during treatment and after drug discontinuation was also reported. Random-effect model and meta-regression analysis were accordingly used. At week 4 after discontinuation, compared with the control group, AOM treatment still had weight loss effect (WMD =  − 0.32 kg, 95% CI − 3.60–2.97, P = 0.85, I2 = 83%). At 8 weeks after drug discontinuation, AOMs were associated with significant weight regain compared with the control group (WMD = 1.50 kg, 95% CI 1.32–1.68, P < 0.0001, I2 = 0.0%). The weight regain trend remained at 12 and 20 weeks (WMD = 1.76 kg, 95% CI 1.29–2.24, P < 0.0001, I2 = 72.0%; WMD = 2.50 kg, 95% CI 2.27–2.73, P < 0.0001, I2 = 0.0%). Among the different subgroups of AOMs, significant weight regain after 12 weeks of drug discontinuation was observed only in studies with glucagon-like peptide 1 receptor agonist (GLP-1 RA) related drugs. In addition, studies in which weight loss was greater during treatment than in the control group and studies in which lifestyle interventions were continued observed significant weight gain after drug discontinuation. Significant weight regain occurred 8 weeks after discontinuation of AOMs and was sustained through 20 weeks. Different weight regain was observed in subjects with different characteristics. Studies with longer follow-up duration are required to further investigate the potential factors associated with weight change after discontinuation of treatment.