Real-world semaglutide (Wegovy) patients might be experiencing a healthcare cost paradox, after a recent analysis in JAMA showed that GLP-1s successfully reduce weight and improve cardiovascular risk factors, but lead to increased patient healthcare expenditures in the short term.
- Semaglutide is a GLP-1 receptor agonist approved for weight management and CV risk reduction, with established cardiovascular benefits in clinical trials like STEP 1.
- The drug has shown dramatic trial results, but real-world cost-effectiveness data has been limited until now.
The real-world analysis examined 23.5k adults prescribed semaglutide between January 2018 and January 2025 across two large U.S. health systems and found over a 13-24 month follow-up that…
- Patients achieved meaningful clinical benefits including 3.8% average weight reduction, 1.5 mmHg diastolic BP decrease, and 12.8 mg/dL total cholesterol reduction.
- However, total monthly healthcare expenditures (excluding drug costs) increased by $80 per patient, with inpatient costs driving approximately half the increase.
- The cost increase was consistent across diabetic ($67/month) and non-diabetic ($81/month) populations.
Even with proven clinical efficacy, the findings reveal a disconnect between immediate clinical benefits and short-term healthcare economics, raising questions about how long GLP-1s take to become cost-effective.
- The increase suggests more hospital visits for cardiometabolic conditions may be driving higher expenditures after medication initiation.
- Real-world weight loss (5% in non-diabetics) was also less dramatic than trial results (nearly 15% in STEP 1), likely due to shorter treatment duration (6-7 months on average).
Given the complexity of real-world GLP-1 use, multiple factors may be influencing the cost-effectiveness equation beyond the medication’s direct clinical effects.
- Drug shortages, coverage changes, and co-pays may contribute to discontinuation patterns that affect long-term cost outcomes.
- Additional healthcare utilization may also come from insurance-mandated follow-up visits, dose adjustments, and increased monitoring.
- The analysis also couldn’t measure how early discontinuation impacts expenditures.
The Takeaway
For a while people have said, “GLP1s are expensive, but they will pay for themselves by reducing downstream healthcare costs.” They probably meant fewer heart attacks and delayed/avoiding chronic diseases (diabetes, HF, etc) and those things might still be true in the long run, but this study does not support that theory within months 13-24.
