From the Guidelines
Patients who have achieved desired weight loss with GLP-1 agonists should continue these medications indefinitely to maintain weight loss and associated health benefits, as discontinuation often results in significant weight regain and worsening of cardiometabolic risk factors. The most recent and highest quality evidence from the 2025 standards of care in diabetes 1 emphasizes the importance of continuing weight management pharmacotherapy, including GLP-1 agonists, beyond reaching weight loss goals to maintain health benefits. This is because obesity is a chronic condition, and GLP-1 agonists work by regulating appetite hormones and glucose metabolism, which, when stopped, can lead to the return of biological drivers of weight gain.
Key points to consider when managing patients on GLP-1 agonists include:
- The potential for significant weight regain after discontinuation of GLP-1 agonists, as seen in clinical trials such as the STEP trials 1, where participants regained approximately 11.6% of lost weight after cessation of semaglutide.
- The importance of individualizing treatment decisions based on patient factors, including medical history, weight maintenance ability, side effects, cost considerations, and personal preferences.
- The need for regular reassessment by healthcare providers to monitor weight, adjust treatment as needed, and address any concerns or side effects.
- The benefits of GLP-1 agonists in improving weight-related comorbidities and reducing the risk of cardiovascular events, as demonstrated in systematic reviews and meta-analyses 1.
In terms of specific treatment strategies, a gradual dose reduction of GLP-1 agonists can be attempted under medical supervision to determine if weight maintenance is possible at a lower dose or without medication. However, the primary goal should be to continue these medications indefinitely to maintain weight loss and associated health benefits, rather than attempting to taper off them after achieving desired weight loss.
From the Research
Weight Loss Effects of GLP-1 Agonists
- The studies 2, 3, 4, 5, 6 suggest that GLP-1 agonists are effective for weight loss in patients with obesity, with or without type 2 diabetes.
- The weight loss effects of GLP-1 agonists can be substantial, with mean weight loss ranging from 4-16 kg 2 and 5-10% or more of initial body weight 4, 6.
Comparison of Different GLP-1 Agonists
- Semaglutide has been shown to have a greater mean weight loss compared to liraglutide and dulaglutide 5.
- Tirzepatide, a dual-agonist, has been shown to have a greater mean weight loss compared to semaglutide 5.
- The most effective GLP-1RA agent for weight loss appears to be semaglutide, with high to moderate GRADE certainty of evidence 6.
Durability of Weight Loss
- The durability of weight loss achieved with GLP-1 agonists is still being evaluated in ongoing studies 2.
- One study found that mean percent weight loss significantly increased from 1.1% at 8 weeks to 2.2% at 72 weeks after GLP-1 agonist dispensing 4.
- Another study found that GLP-1RAs had nonlinear dose-response relationships with weight loss, and trial sequential analysis supported conclusive evidence of the effects of GLP-1RAs on weight loss 6.