Real-world estimates showed that up to 75% of patients discontinued glucagon-like peptide-1 receptor agonists within 12 months of initiation, according to a viewpoint published in JAMA by Khan, Ndumele, and Kazi.
A national survey revealed that 12% of U.S. adults reported prior glucagon-like peptide-1 receptor agonist (GLP-1 RA) use, with 6% reporting current use. The SELECT trial documented a 30% discontinuation rate for semaglutide, while real-world data indicated discontinuation rates between 50% and 75% at 12 months.
Clinical data from the STEP-1 extension and STEP-4 trials demonstrated that patients regained two-thirds of lost weight following semaglutide discontinuation. Laboratory parameters, including glucose levels, blood pressure, and cholesterol levels, also worsened after cessation of the medication.
Medicare expenditures for newer high-potency GLP-1 RAs increased 100-fold from 2018 to 2022. U.S. list prices for 4-week supplies of semaglutide or tirzepatide formulations ranged from $900 to $1,350.
The findings indicated that monthly copayments affected continuation rates significantly. Patients paying $50 or more monthly showed a lower risk of GLP-1 RA adherence at 1 year compared with those paying under $10 (adjusted odds ratio = 0.47, 95% confidence interval = 0.44–0.51).
The treatment-eligible population included approximately 140 million U.S. adults. Gastrointestinal adverse effects occurred in 20% to 44% of users during early treatment, typically resolving within months.
Survey data showed that patient interest dropped from 45% to 14% when informed about postdiscontinuation weight regain.
The analysis identified several policy challenges:
- Time-limited coverage requirements
- Restrictive prior authorization processes
- More limited coverage for weight management vs diabetes
- Ongoing drug shortages leading to involuntary discontinuation
- Variable out-of-pocket costs ranging from under $50 to over $500 monthly.
The Inflation Reduction Act's planned $2,000 annual out-of-pocket drug cost cap for Medicare Part D beneficiaries in 2025 excluded those with other insurance types or without insurance.
The lead author reported receiving grants from the National Heart, Lung, and Blood Institute and American Heart Association. No other disclosures were reported.
