From the Guidelines
Most patients will regain a significant amount of weight after stopping GLP-1 agonists, with a mean weight regain of 11.6% of lost weight within 52 weeks of discontinuation, as seen in the STEP 1 trial 1. This occurs because GLP-1 agonists work by suppressing appetite, increasing feelings of fullness, and slowing gastric emptying—effects that disappear when the medication is stopped. The body also tends to defend against weight loss through metabolic adaptation. To improve chances of maintaining weight loss after stopping these medications, patients should implement comprehensive lifestyle changes during treatment, including:
- Establishing sustainable dietary habits
- Regular physical activity (150+ minutes weekly)
- Behavioral strategies
- Possibly transitioning to maintenance medications Some clinicians recommend a slow taper rather than abrupt discontinuation. Patients should understand that these medications may require long-term or indefinite use for sustained results, similar to treatments for other chronic conditions like hypertension or diabetes, as supported by the recent review on obesity management in adults 1. The use of long-term antiobesity medications is recommended when weight maintenance is inadequate with lifestyle interventions alone, as stated in the recent review on obesity management in adults 1. It is essential to note that the effects of GLP-1 agonists on weight loss and weight-related comorbidities are significant, but the weight regain after discontinuation highlights the need for a comprehensive approach to obesity management, including lifestyle modifications and potentially long-term medication use, as seen in the study on semaglutide and liraglutide 1.
From the Research
Weight Loss Maintenance with GLP-1 Agonists
- Patients who achieve weight loss with GLP-1 agonists may be able to maintain this weight loss after discontinuing the medication, particularly if they transition to other anti-obesity medications 2.
- A real-world study found that patients who had achieved successful weight loss with GLP-1 receptor agonist therapy were able to maintain their weight loss after transitioning to generic anti-obesity medications 2.
- However, another study suggested that the real-world benefit of GLP-1 agonists on weight loss may be lower than that observed in clinical trials, with only a minority of patients achieving ≥5% weight loss 3.
Factors Affecting Weight Loss Maintenance
- Adherence to GLP-1 agonist therapy is an important factor in achieving and maintaining weight loss, with suboptimal adherence potentially limiting the effectiveness of treatment 3.
- The cost of GLP-1 agonists can be a significant barrier to access and may limit their use, highlighting the need for cost-effective alternatives 2, 4.
- GLP-1 agonists have been shown to have beneficial effects on cardiometabolic risk factors, including glycemic control and blood pressure, in addition to their weight loss effects 4, 5.
Evidence for Weight Loss Maintenance
- A systematic review and meta-analysis of randomized controlled trials found that treatment with GLP-1 receptor agonists resulted in significant weight loss in overweight or obese patients with or without type 2 diabetes mellitus 5.
- Other studies have also demonstrated the effectiveness of GLP-1 agonists for weight loss, with some agents achieving mean weight losses of 4-16 kg 6, 4.