By Jason Peterson, RPh; Beckie Fenrick, PharmD, MBA; and Emily Crisano, PharmD, RPh
As GLP-1 medications like Wegovy, Zepbound and Saxenda dominate headlines, many plan sponsors are weighing whether the clinical benefits justify the steep and sustained price tag. With more than 40% of U.S. adults affected by obesity, the demand for effective weight management therapies is real—but so are the concerns about long-term value, member outcomes and return on investment.
This article examines the latest clinical, economic and real-world evidence on GLP-1 and GIP/GLP-1 receptor agonists to help payers and benefit leaders make informed decisions about coverage and cost containment.
Comparing GLP-1 Therapies: Clinical and Cost Snapshot
Several GLP-1 and GIP/GLP-1 receptor agonists have been FDA-approved specifically for chronic weight management, but their efficacy and costs vary widely. Below is a side-by-side comparison of three leading therapies.
Brand Name | Saxenda | Wegovy | Zepbound |
Mechanism | GLP-1 | GLP-1 | GIP/GLP-1 |
Generic name | liraglutide | semaglutide | tirzepatide |
Average Body Weight Reduction | 7% of body weight after 56 weeks | 16% of body weight after 68 weeks | 20% of body weight after 72 weeks |
Mfg. Copay Card | Yes | Yes | Yes |
Annual List Price (WAC) | $17,537 | $17,537 | $14,123 |
Estimated Annual Net Price* | $9,958 | $8,021 | $9,425 |
*Assumes maximum discounts and rebates; source: SSR Health, Inc. (ICER, 2025)
Real-World GLP-1 Use: What Happens Outside the Clinical Trial Setting
Adherence and Persistence
Adherence is a critical—and often overlooked—factor in coverage decisions. Data from Evernorth and Prime Therapeutics reveal high early drop-off rates:
- >50% of users discontinue therapy within a year.
- 32% remain on therapy at one year; only 8% persist through year three.
- Leading reasons for discontinuation include side effects (43.7%), perceived lack of necessity (40.1%), and cost or coverage issues (30.9%).
Weight Regain and Body Composition
Rapid weight regain is common after stopping therapy, with a portion of users regaining as much as 50% of lost weight within a year—and some returning to baseline within two. Up to 60% of weight lost with GLP-1s may be lean mass, and the weight regained can be concerning as lean mass is typically not regained during the rebound. Maintaining physical activity and resistance training during and after treatment is key to preserving one’s muscle mass.
Side Effects
Certain people utilizing GLP-1s also experience unpleasant side effects including: nausea (>33%), vomiting, diarrhea, and constipation (25%) and hair loss (>5% at high Zepbound doses)
All three medications present a risk for medullary thyroid carcinoma (MTC) and carry boxed warnings for patients with a history of MTC or multiple endocrine neoplasia type 2(MEN2) .
Cost-Effectiveness: Shifting Targets and Uncertain Returns
ICER’s initial review concluded that Wegovy was not cost-effective at its $13,000 annual net price. Recent net prices (assuming maximum rebates) may fall within ICER’s target range of $7,500–$9,800, though these discounts are not universally available.
Key findings from additional cost-effectiveness research with conclusions that differ from the ICER study include:
- A 2023 study found that Wegovy and Zepbound were not cost-effective, while Qsymia emerged as the most cost-effective option.
- A 2024 study estimated that to meet cost-effectiveness thresholds, Wegovy and Zepbound would need annual net prices of $1,522 and $4,334, respectively.
These assessments rely on short-term clinical data, not long-term or real-world use, which limits their real-world applicability.
Further complicating cost effectiveness assessments, a two-year persistence study by Prime Therapeutics found that GLP-1 users incurred significantly higher total healthcare costs compared to controls—due to both drug and medical expenses. Long-term benefits like reduced diabetes or cardiovascular risk may take years to materialize and rely on sustained weight loss.
Other Options for Payer Consideration
Lower-Cost Medications
While GLP-1s are high-profile, several oral agents offer lower-cost alternatives with favorable cost-effectiveness in certain populations.
According to ICER’s 2022 review, Qsymia was the most cost-effective agent among the drugs studied. At a wholesale acquisition cost (WAC) of $224/month, with generics available for as low as $96, Qsymia offers a more affordable option. Contrave (naltrexone-bupropion) is another oral agent, currently priced at $625 WAC/month.
Direct-to-Consumer Models
Wegovy and Zepbound are now available directly to consumers from their manufacturers at a flat monthly rate as low as $499. However, these programs are limited to self-paying individuals and are not applicable to plan sponsors andSaxenda does not offer this distribution models.
Behavior Support Programs
Sustainable weight loss often depends on long-term behavior change. Programs offering support with diet, exercise, and lifestyle changes can help patients maintain progress after stopping medication and may improve initial outcomes when used alongside therapy.
Key Questions for Coverage Decisions
Determining whether to cover GLP-1 therapies requires careful consideration of:
- Member population characteristics
- Expected adherence and persistence
- Availability of lifestyle or behavior support
- Short-term affordability vs. long-term value
Cost-effectiveness varies across populations and usage patterns. Evidence to date suggests that while GLP-1s may offer meaningful weight loss, high costs, low persistence, and rebound risk limit their long-term value for many plans.
If you’re weighing the role of weight management therapies in your benefit design, Navion can help you navigate the trade-offs with clarity and confidence.