Published on March 3 , 2025 | 4 Minutes to Read
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Few medications have experienced a rise as meteoric as semaglutide (Ozempic, Wegovy) and tirzepatide (Zepbound), the GLP-1-based treatments for obesity that have captivated society and quickly become household names. These drugs represent a significant advancement in obesity medicine. Until semaglutide’s 2021 FDA approval for chronic weight management, the most effective medication was arguably phentermine (Adipex), first approved in 1959. After more than six decades with little progress, it’s no surprise that both patients and doctors saw GLP-1s as a long-awaited breakthrough.
The reality of GLP-1s: Effective but unsustainable
From an efficacy standpoint, there is no denying that GLP-1 medications “work.” Those who can afford, tolerate, and sustain GLP-1 use do lose weight. The benefits extend beyond weight loss: studies confirm reductions in cardiovascular events and improvements in conditions such as congestive heart failure, kidney disease, obstructive sleep apnea, and osteoarthritis. The benefits of these drugs cannot be denied—when they are taken indefinitely. But what happens when patients stop taking them? This is where the problem lies.
Most patients do not stay on anti-obesity medications long-term. Research shows that three-quarters of patients stop GLP-1 medications within two years, many within just months. Reasons for discontinuation include cost, side effects, and supply shortages. However, one of the most common reasons is that patients simply do not want to take a weight loss medication indefinitely. Many believe they can use these drugs temporarily, change their lifestyle, and stop taking them without regaining weight.
Unfortunately, that is not the reality. Clinical trials of semaglutide and tirzepatide show that the average patient regains two-thirds of the weight lost within the first year of discontinuation. For some, the return of weight feels almost instantaneous, and they often regain more than they initially lost. Patients describe feeling ravenous and overwhelmed by the resurgence of food noise.
Why weight regain happens
The science behind GLP-1 medications explains why they do not create permanent change. These drugs are exogenous, synthetic agonists of the glucagon-like-peptide-1 receptor. While in use, they saturate those receptors—particularly in the brain and stomach—mimicking the effects of endogenous GLP-1 at sky-high, sustained levels. Once the medication is stopped, that effect disappears within two to four weeks. The receptors are no longer bathed in hunger-calming peptides. Hunger returns—with a vengeance. And the weight quickly follows.
As a result, many patients cycle on and off treatment, and in the end, the only thing they lose is money—upwards of $400 per year (if their insurance does not cover it, and most plans do not).
The broader implications of GLP-1 dependence
This cycle of weight loss and regain has profound long-term implications for physical, mental, and economic health. What happens to society when millions of people are exposed to short-term GLP-1 use? Are we ultimately violating medicine’s most basic rule: do no harm?
While on treatment, patients lose lean muscle along with fat, and studies suggest that much of that muscle loss is never recovered. When weight is regained, it is primarily fat, not muscle. This can leave patients worse off— with less lean mass, a lower basal metabolic rate, and greater difficulty achieving future weight loss. The health consequences include diminished strength, reduced bone density, and a higher risk of fractures.
Weight regain reinforces myths and stigmas surrounding obesity. Patients often blame themselves for another “failed” attempt, leading to depression and declining self-confidence. This cycle exacerbates the very struggles that led them to seek treatment in the first place.
The financial cost of cycling on and off these medications is staggering. Individuals make significant sacrifices to spend thousands of dollars annually on GLP-1s, only to regain the weight. On a larger scale, the economy cannot sustain these ballooning costs. States across the country are already suspending insurance coverage due to unsustainable expenses.
Final thoughts
GLP-1 medications are a remarkable tool, but they are not the ultimate answer to obesity. The way forward must involve comprehensive, sustainable solutions that address long-term metabolic health without creating dependency. Otherwise, we may be setting ourselves up for a crisis far greater than the one we are trying to solve.
References
https://www.medpagetoday.com/opinion/second-opinions/114009?trw=no
https://pubmed.ncbi.nlm.nih.gov/35441470/
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