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Weight Loss from GLP-1 Drugs Regained After Discontinuation, Studies Show

• Clinical trials indicate that weight loss achieved with GLP-1 drugs like semaglutide and tirzepatide is often regained after patients stop taking the medication. • Studies such as the Step 1 trial extension and Surmount-4 trial demonstrate significant weight regain despite initial success with GLP-1 agonists. • Experts emphasize that obesity should be treated as a chronic disease, requiring long-term management strategies, similar to hypertension or hyperlipidemia. • Strategies to maintain weight loss after discontinuing GLP-1 drugs are lacking, highlighting the need for individualized approaches and further research.

Weight loss medications such as GLP-1 drugs like Ozempic and Mounjaro initially promised a breakthrough in obesity treatment, but recent studies reveal a significant challenge: weight is often regained after discontinuing the medication. Clinical trials indicate that without continuous use, the benefits of these drugs diminish, leading to a resurgence of weight. This has prompted experts to view obesity as a chronic condition requiring ongoing management, much like hypertension or hyperlipidemia.

Clinical Trial Evidence

The Step 1 trial extension, involving 1,961 adults without diabetes, demonstrated that while participants initially lost an average of 14.9% of their body weight over 16 months using semaglutide, they regained 11.6% of their original weight after stopping the drug and lifestyle counseling. This resulted in a net weight loss of only about 8.4 lbs for an average 150 lb person after two years.
Similarly, the Surmount-4 Trial examined tirzepatide (Zepbound), a combination of a GLP-1 agonist and an insulin agonist. Patients on tirzepatide for 36 weeks experienced an average weight loss of nearly 21%. However, when switched to a placebo, they regained weight, resulting in a net loss of only about 10% of their original body weight. Dr. Robert Kushner from Northwestern University Feingold School of Medicine emphasized that these results underscore the biological nature of obesity and the importance of continuous medication to manage the condition.

Expert Perspectives

John Wilding, DM, from Aintree University Hospital, likened obesity treatment to managing high blood pressure or high cholesterol. He noted that when patients discontinue antihypertensive or cholesterol-lowering drugs, their blood pressure and cholesterol levels return to previous, elevated levels. He suggests obesity should be viewed similarly, requiring continuous intervention.
Nate Wood, MD, MHS, at the Yale School of Medicine, supports this view, stating that obesity is a chronic disease necessitating chronic treatment. Clinical trials have consistently shown that weight lost with GLP-1 drugs is regained upon discontinuation.

Challenges of Long-Term Drug Usage

While continuous use of GLP-1 drugs helps maintain weight loss, it presents challenges. These include fitting the medication into an individual’s lifestyle, managing potential gastrointestinal side effects, and the need for careful dose adjustments to avoid rapid weight loss that can lead to complications like gallstones or muscle mass loss. Additionally, discontinuing the drug can trigger mental health issues, such as intense cravings and a sense of starvation.

Strategies for Weight Loss Maintenance

Currently, there is limited data on specific strategies to maintain weight loss after discontinuing GLP-1 drugs. Abruptly stopping medication is not advised, as demonstrated by the cited studies where doses were not tapered. Individualized discussions and creative solutions are essential for long-term weight management. Potential strategies include dose-tapering, intermittent therapy, using different, older drugs, or more intensive lifestyle modifications.

Guidance for Patients

Patients receiving or considering GLP-1 treatment should maintain regular consultations with their prescribing doctor. Open communication, asking questions, and discussing personal ideas and beliefs are crucial. Patients should also be honest about their willingness to commit to the lifestyle changes necessary to maintain or continue weight loss, even when not taking the medication.
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