Patient Challenges with GLP-1 Drugs: Exploring Discontinuation Reasons

Weight regain and worsening cardiometabolic status are significant risks when patients stop using GLP-1 drugs. Unfortunately, too few physicians are addressing this issue, according to a recent JAMA viewpoint.

Interest in GLP-1 receptor agonists has grown rapidly, primarily due to their weight loss and cardiovascular benefits, as demonstrated in the SELECT trial. However, it is estimated that 50% to 75% of patients discontinue treatment within a year, often leading to weight rebound and a decline in cardiometabolic health.

The viewpoint highlights the importance of understanding the reasons behind discontinuation and finding ways to keep patients on these medications long-term. While cost and side effects are among the primary reasons for discontinuation, a lack of clear communication about the need for chronic use also plays a role.

From a research perspective, exploring barriers like cost, the injectable form of therapy, and supply challenges could reveal strategies to improve adherence. It's crucial to quantify whether short-term therapy has any lasting benefit or if it leads to a return to pretreatment risk or even increased risk after discontinuation.

At the clinical level, physicians should frame the decision to start GLP-1 receptor agonists with a long-term, chronic perspective, ensuring strategies are in place to support patients’ adherence and maintain the benefits over time. Equitable access to these medications is also a priority, given the high out-of-pocket costs and insurance restrictions.

Policy considerations include addressing the high cost of GLP-1s in the US, pricing discrepancies with other countries, and drug shortages. Although GLP-1 usage is likely to increase, high discontinuation rates should prompt attention from clinicians, policymakers, and public health experts. A focus solely on equitable initiation is not enough; strategies are needed to improve long-term adherence for the benefit of population health.

Future considerations include the potential for lower dosing in some patients, less frequent injections, or oral formulations that may enhance adherence. Lifestyle modifications may also play a supportive role in combination with GLP-1s.

Clear, up-front communication between physicians and patients about treatment expectations is vital for sustaining the long-term use of GLP-1 receptor agonists. This discussion is often lacking in the weight-loss setting, but it is key for better adherence.

Take-Home Points:

• Long-term adherence to GLP-1 drugs is crucial to prevent weight regain and cardiometabolic deterioration.
• Cost, side effects, and lack of clarity around the need for chronic use are leading causes of discontinuation.
• Future approaches include lower doses, oral formulations, or less frequent dosing.
• Effective communication between patients and physicians is essential for supporting adherence.

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