When is it appropriate to discontinue Glucagon-like peptide-1 (GLP1) receptor agonist medication, such as liraglutide (glucagon-like peptide-1), in a patient who has reached their weight loss goal and plateaued?

From the Guidelines

The decision to discontinue a GLP-1 receptor agonist like liraglutide after reaching weight loss goals should be individualized and made in consultation with a healthcare provider, with a general recommendation to continue the medication indefinitely if it's being well-tolerated and providing clinical benefit, as supported by the most recent evidence from 2022 1 and 2023 1. When considering discontinuation, it's essential to weigh the benefits of continued weight management against potential side effects and the risk of weight regain.

• The medication should not be abruptly discontinued once weight loss plateaus, as weight regain is common following discontinuation, with patients often regaining 2/3 of the lost weight within the first year after stopping, as noted in the 2022 study 1.
• A gradual tapering approach may be considered, such as reducing liraglutide from 3.0 mg to 1.8 mg daily for several weeks before further reductions, as suggested by the 2023 evidence 1.
• Patients should be closely monitored during this process, and the biological reason for weight regain is that GLP-1 agonists work by regulating appetite centers in the brain and slowing gastric emptying, effects that cease when the medication is stopped.
• Additionally, these medications often provide metabolic benefits beyond weight loss, including improved glycemic control and cardiovascular risk reduction, which may warrant continued use even after weight stabilization, as highlighted in the 2022 guideline 1 and the 2023 consensus 1.
• The 2023 study 1 also emphasizes the importance of monitoring for potential side effects, such as nausea, vomiting, and hypoglycemia in patients with type 2 diabetes treated with insulin and/or sulfonylureas.
• The 2022 guideline 1 provides further guidance on the use of GLP-1 receptor agonists, including liraglutide, for chronic weight management, highlighting the need for individualized treatment plans and close monitoring of patients.

From the FDA Drug Label

Instruct adult patients to discontinue SAXENDA if they have not achieved 4% weight loss by 16 weeks of treatment.

The FDA drug label does not provide guidance on when to discontinue GLP1 receptor agonist medication, such as liraglutide, in a patient who has reached their weight loss goal and plateaued. The label only provides instructions to discontinue the medication if the patient has not achieved a certain percentage of weight loss by a specified timeframe.

• Discontinuation criteria are only based on lack of efficacy, not on achieving a weight loss goal.
• There is no clear guidance on how to manage patients who have reached their weight loss goal and plateaued.
• Clinical decision should be made on a case-by-case basis, taking into account the individual patient's needs and risk factors 2.

From the Research

Discontinuation of GLP-1 Medication After Reaching Weight Loss Goal

• The decision to discontinue GLP-1 receptor agonist medication after reaching a weight loss goal is complex and depends on various factors, including the individual's health status, weight loss maintenance, and potential side effects 3, 4.
• Studies have shown that discontinuation of GLP-1 receptor agonist medication can lead to weight regain, highlighting the importance of considering long-term weight loss maintenance strategies 4, 5.
• The addition of supervised exercise to obesity pharmacotherapy, such as GLP-1 receptor agonist medication, may improve healthy weight maintenance after treatment termination compared to treatment termination of obesity pharmacotherapy alone 4.

Factors Associated with Discontinuation and Reinitiation of GLP-1 Medication

• Higher weight loss and higher income are associated with lower rates of discontinuation of GLP-1 receptor agonist medication, while moderate or severe incident gastrointestinal adverse events are associated with a higher hazard of discontinuation 5.
• Weight regain after discontinuation of GLP-1 receptor agonist medication is significantly associated with increased hazards of reinitiation, highlighting the importance of monitoring weight changes after treatment termination 5.

Mechanisms of GLP-1-Induced Weight Loss

• GLP-1 receptor agonist medication, such as liraglutide, has been shown to reduce appetite and energy intake, rather than increasing energy expenditure, which may contribute to its weight loss effects 6.
• The effects of GLP-1 receptor agonist medication on gastric emptying, glycemic parameters, and energy metabolism may also play a role in its weight loss effects, although the exact mechanisms are not fully understood 6.

Considerations for Discontinuation of GLP-1 Medication

• The decision to discontinue GLP-1 receptor agonist medication should be made on a case-by-case basis, taking into account the individual's health status, weight loss maintenance, and potential side effects 3, 4.
• Further research is needed to understand the long-term effects of GLP-1 receptor agonist medication on weight loss maintenance and overall health outcomes, as well as the optimal strategies for discontinuation and reinitiation of treatment 3, 5.