How to safely discontinue Glucagon-like peptide-1 (GLP-1) agonists in patients?

From the Guidelines

To safely discontinue GLP-1 agonists, patients should follow a gradual tapering schedule under medical supervision rather than stopping abruptly, with the most recent and highest quality study suggesting a tapering approach to minimize risks and complications 1.

Tapering Schedule

For weekly medications like semaglutide (Ozempic, Wegovy) or dulaglutide (Trulicity), patients should:

• Reduce to every 10-14 days for 2-4 weeks before stopping completely For daily medications like liraglutide (Victoza, Saxenda) or exenatide (Byetta), patients should:
• Reduce to half the dose for 1-2 weeks before discontinuation

Monitoring and Precautions

During this tapering period, patients should:

• Monitor blood glucose levels more frequently, especially those with diabetes, as levels may rise after discontinuation 1
• Expect potential weight regain of 2-3% within the first month and possibly more over time
• Be aware of the potential increased risk of pulmonary aspiration, particularly in the peri-operative setting 1

Transition to Sustainable Lifestyle

A transition to a sustainable diet and exercise plan is crucial during this period to minimize weight regain and maintain glucose control.

Gastrointestinal Symptoms

Gastrointestinal symptoms like nausea or constipation typically resolve within 1-2 weeks after stopping, but patients should be monitored for any persistent or severe symptoms 1. The tapering approach is recommended because it allows the body to adjust gradually to changing hormone levels, reducing the risk of blood sugar fluctuations and minimizing rebound hunger or gastrointestinal distress that can occur with sudden discontinuation.

From the Research

Discontinuing GLP-1 Agonists

To safely discontinue Glucagon-like peptide-1 (GLP-1) agonists in patients, consider the following:

• The decision to discontinue GLP-1 agonists should be based on individual patient needs and clinical judgment, as there is limited evidence to support specific discontinuation guidelines 2.
• Discontinuation of GLP-1 receptor agonist (GLP-1 RA) treatment can lead to significant weight regain, which should be discussed with patients when stopping therapy 3.
• Weight regain after discontinuing GLP-1 RA therapy is proportional to the original weight loss, with participants taking liraglutide regaining 2.20 kg and those taking semaglutide/tirzepatide regaining 9.69 kg 3.

Factors Associated with Discontinuation

Factors associated with discontinuation of GLP-1 RAs include:

• Higher weight loss, which is associated with lower rates of discontinuation 4.
• Higher income, which is associated with lower rates of discontinuation in patients with type 2 diabetes 4.
• Moderate or severe incident gastrointestinal adverse events, which are associated with a higher hazard of discontinuation 4.

Reinitiation of GLP-1 RAs

Reinitiation of GLP-1 RAs after discontinuation is associated with:

• Weight regain, with a 1% weight regain from discontinuation associated with increased hazards of reinitiation 4.
• Lower reinitiation rates in patients without type 2 diabetes compared to those with type 2 diabetes 4.

Clinical Considerations

When considering discontinuation of GLP-1 agonists, clinicians should:

• Balance the potential risks and benefits of discontinuation, including the risk of pulmonary aspiration and the potential for worsening glycemic control 2.
• Consider alternative approaches to managing patients undergoing elective surgery, such as a multidisciplinary approach to manage patients undergoing elective surgery 2.
• Be aware of the potential for significant weight regain after discontinuation and discuss this with patients when stopping therapy 3.