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When does the weight loss plateau occur on drugs like Ozempic, and can you delay it?

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When is a person likely to reach a weight loss plateau on GLP-1 agonists vs surgery vs dietary interventions? Image credit: Guillermo de la Torre/Stocksy.
  • A new study investigated why different obesity treatments, including diets, surgeries and new medications like GLP-1 receptor agonists, such as semaglutide and tirzepatide, lead to varying times at which weight loss plateaus.
  • Utilising a mathematical model, the research examines how these interventions alter the body’s regulation of energy intake and expenditure, affecting the duration of effective weight loss.
  • The findings reveal that interventions like bariatric surgery and GLP-1 medications may extend the period of weight loss significantly longer than traditional diets by modifying the body’s appetite control mechanisms, highlighting the complexity of how different treatments interact with our physiological systems.

This new research, published in Obesity Trusted Source Wiley Peer reviewed journal Go to source , focuses on understanding why different obesity treatments stop showing weight loss results at different times, known as a weight plateau.

The study focused on new medications called glucagon-like peptide 1 (GLP-1) receptor agonists, like semaglutide (brand names Ozempic, Wegovy) and tirzepatide (brand names Zepbound, Mounjaro), which continue to help people with chronic conditions like diabetes and obesity lose weight for over a year without hitting a plateau.

In contrast, traditional dieting methods usually reach a weight loss plateau within about 12 months, similar to what is observed with bariatric surgery, although the latter tends to extend the weight loss period longer than dieting alone.

GLP-1 agonists vs diet and surgery

The researcher used a mathematical model previously developed for understanding human energy metabolism and body composition and modified it to examine how various weight loss interventions — like diets, surgery, and medication — affect the way our body regulates energy intake.

By inputting average data from existing studies on different interventions, such as intensive calorie restriction, various diets and medications like semaglutide and tirzepatide, the model simulates how these interventions lead to changes in energy intake and expenditure over time.

The goal was to understand and quantify how these interventions disrupt the body’s normal appetite control, thus extending or shortening the period of weight loss before reaching a plateau.

The findings suggest that different weight-loss interventions interact uniquely with the body’s natural mechanisms that control energy intake and expenditure.

Initially, interventions like diet restriction, medication (semaglutide, tirzepatide), and surgery (Roux-en-Y gastric bypass, or RYGB) decrease energy intake significantly.

However, over time, the body’s feedback system, which stimulates appetite in response to weight loss, begins to counteract this reduction in energy intake.

This leads to a gradual increase in energy intake until it matches energy expenditure, resulting in a weight-loss plateau.

Surgery, GLP-1 agonists lead to more sustained weight loss

The study suggests that RYGB surgery showed a much larger and longer-lasting effect compared to diet restrictions, and medications like tirzepatide and semaglutide also demonstrated a prolonged period of effective weight loss.

This is largely due to these interventions reducing the feedback control of appetite by about 40% to 70%, which delays the time it takes to reach the weight-loss plateau.

Mir Ali, MD, bariatric surgeon and medical director of MemorialCare Surgical Weight Loss Center at Orange Coast Medical Center in Fountain Valley, CA, not involved in the research, told Medical News Today that the study is “consistent with [his] experience treating obesity both with surgery and medications.”

Does the study reflect real-life situations?

The study suggests the dynamic and complex nature of how different interventions impact the body’s energy balance over time. However, other experts, also not involved in the research, highlighted several limitations.

Jared Ross, DO, a professor and medical director at the Henry Ford College Paramedic Program and the medical director for Trauma Services at Bothwell Regional Health Center in Missouri, said that, “while this is an interesting study, it is significantly limited by the fact that it uses mathematical models of energy metabolism to simulate weight loss and fat loss.”

“Actual human weight loss and weight loss plateaus are very complicated and highly variable between individuals and not likely well stimulated by models,” Ross explained. “There are multiple compounding factors here. Diet restriction suffers from noncompliance and reporting biases.”

“Semaglutide and tirzepatide, the GLP-1 agonists are relatively new medications and we have limited data about the long-term effects of these medications as well significant questions about maintaining weight loss once patients discontinue the medication. Roux-en-Y gastric bypass additionally has multiple complicating factors including the fact that many patients suffer excessive and rapid weight loss and struggle with malnutrition and dumping syndrome. Other patients with Roux-en-Y gastric bypass may ‘cheat’ and consume additional calories in the form of smoothies or calorie dense liquids.”

– Jared Ross, DO

Dr. Ross noted that although this study is interesting, “it is significantly limited by the fact that it is only mathematical models, and does not account for real-life human behavior.”

What might postpone the weight loss plateau?

Kelsey Costa, MS, RDN, a registered dietitian nutritionist and founder of Dietitian Insights, also not involved in this research, told MNT that “the physiology of weight loss plateaus, as detailed in this study, suggests that weight-loss interventions like RYGB surgery, tirzepatide, and semaglutide significantly weaken the feedback control of appetite, leading to prolonged periods of weight loss before a plateau is reached.”

“This was contrasted with the restriction of calories or macronutrients, which tend to result in plateaus within about 12 months due to the body’s feedback mechanisms that regulate energy intake and expenditure,” she added.

Costa also noted that “[i]ncorporating dietary methods such as intermittent fasting Trusted Source PubMed Central Highly respected database from the National Institutes of Health Go to source  could potentially extend the time to a weight loss plateau by inducing changes in energy efficiency and hormone levels that influence appetite and metabolism.”

“By cycling between periods of eating and fasting, the body may shift towards burning fat for energy more efficiently, bypassing the body’s traditional energy conservation mechanisms that often lead to early plateaus in a calorie-restricted diet. This method, coupled with its ability to improve insulin sensitivity, adds a valuable tool in the arsenal against obesity, especially when used in conjunction with other lifestyle modifications.”

– Kelsey Costa, MS, RDN

She added that “the extension of fasting periods to ranges between 18 to 72 hours could significantly delay the onset of a weight loss plateau by further enhancing the body’s metabolic adaptability.”

Costa further cautioned that “[t]his study uses mathematical modeling to simulate how different obesity treatments might impact body weight, composition, and energy balance dynamics without testing these interventions in real-life scenarios.”

“The present study did not explore dietary interventions beyond calorie or macronutrient restrictions, leaving room for future research into the comprehensive effects of various weight-loss strategies,” she pointed out.

‘Dietary changes remain essential’ for weight loss

Costa explained that “understanding these dynamics can help set realistic expectations and guide more effective long-term weight management plans.”

Ross added that “the potential implications for patients and physicians are very limited and additional real-life research will need to be conducted to compare GLP-1 agonists to Roux-en-Y surgery.”

“It is fairly clear from other research that both of these treatment options are significantly more efficacious than dietary restriction, but the long-term implications of GLP-1 agonists has yet to be seen,” he noted. “Additionally, there are numerous patient-specific factors to take into account when determining the best obesity treatment for a patient including GLP-1 agonist versus Roux-en-Y gastric bypass surgery.”

Costa pointed out that “in almost all cases, dietary changes remain essential both before and after other interventions.”

“They serve as the initial and ongoing foundation for promoting lifelong health and sustainable weight management. When used as the primary intervention, individuals making diet changes can significantly improve their overall health while avoiding the potential side effects associated with surgical and pharmaceutical options. However, for some individuals, a multidisciplinary approach may be essential to achieve long-term success.”

– Kelsey Costa, MS, RDN

This article originally appeared on Medical News Today.

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