The first clinical trial directly comparing weight-loss drugs Zepbound and Wegovy has confirmed previous placebo-controlled trial results indicating that adults taking Zepbound experience greater weight loss. 

According to Zepbound’s manufacturer Eli Lilly, who conducted the study, (opens a new window) the head-to-head trial showed that, on average, Zepbound resulted in a 20.2% weight loss, compared to 13.7% with Wegovy.   

The clinical superiority of Zepbound, alongside expanding indications for both drugs, has the potential to drive increased consumer demand, intensify competition for rebates, and prompt changes to existing coverage. These shifts could significantly impact health plans and pharmacy benefits, influencing both pricing and availability for both Zepbound and Wegovy. It’s crucial for employers to understand these changes and assess their effects on the overall benefits strategy and employee experience.    

Zepbound vs. Wegovy: What’s the difference? 

Although Zepbound and Wegovy are both anti-obesity medications used for chronic weight management, their clinical efficacy varies because Zepbound (opens a new window) contains tirzepatide, while Novo Nordisk’s Wegovy (opens a new window) contains semaglutide.  

One possible reason for Zepbound’s superiority is the dual effect of tirzepatide, which mimics two hormones. Semaglutide has a single effect, mimicking one hormone.

Additional indications 

Both medications have already received FDA approval for additional indications (opens a new window) beyond weight loss, with more approvals expected in the future: 

• Wegovy (opens a new window) was approved to reduce the risk of cardiovascular death, heart attack and stroke in adults with overweight or obesity with preexisting cardiovascular disease and is also being evaluated for the treatment of Alzheimer’s disease, nonalcoholic steatohepatitis (fatty liver disease), and osteoarthritis.  

• Zepbound (opens a new window) was approved for the treatment of moderate to severe obstructive sleep apnea (OSA) in adults with obesity and is also being evaluated for the treatment of chronic kidney disease and nonalcoholic fatty liver disease. 

Cost and prevalence 

Wegovy launched in June 2021, gaining a significant first-to-market advantage over Zepbound, which became available in November 2023.  

This early entry allowed Novo Nordisk to build strong brand recognition for Wegovy and capture a larger market share at a higher price point than Lilly.  

According to Infolock® data of over 4.3 million lives across Lockton’s book of business, Wegovy was prescribed approximately three times as often as Zepbound, and cost 42% more than Zepbound on average from July 2023 to June 2024. 

Neither have generic alternative options available at a lower cost, and likely won’t until the mid-2030s at the earliest. 

Post-trial implications: What could Zepbound’s clinical advantage mean for employers and benefits? 

Changes in market demand 

Lilly is now strategically positioned to utilize their recent clinical trial results in direct-to-consumer advertising. Highlighting Zepbound’s clinical appeal and lower cost in marketing efforts could increase consumer demand by prompting more patients to request Zepbound from their healthcare providers. Additionally, healthcare providers who specialize in obesity may prioritize prescribing a clinically superior product, potentially flipping current market dynamics. 

Competition for bundled rebates 

Pharmaceutical rebates are typically influenced by market share—the more a product is used, the higher the rebate. If demand for Zepbound increases, financial incentives and negotiations for both Zepbound and Wegovy may shift. Pharmacy benefit managers (PBMs) and manufacturers have had exclusive relationships, as was historically seen with insulin. This is likely to continue, where PBMs may choose to align with one manufacturer (e.g., Lilly) and exclude competitors (e.g., Novo Nordisk's) or vice versa. 

Availability and coverage 

More affordable, off-brand versions of Zepbound have been available at compounding pharmacies due to a supply shortage.  But after two years, The FDA announced (opens a new window) Zepbound’s active ingredient tirzepatide is fully available again, and compounders will have to stop making the off-brand drugs by February or March of 2025. A decision on semaglutide’s shortage status is expected in the first few months of 2025.   

Formulary placements, expanding indication approvals, direct-to-patient option Lilly Direct, head-to-head study results, and competitive pressures will continue to affect access and coverage of Zepbound and Wegovy. 

Future planning: How can employers navigate ongoing changes?

While the recent trial and growing consumer demand may spark interest in favoring or adding coverage for one drug over another, it’s important to note that PBM and carrier contracts often limit the ability to dictate coverage at the therapeutic level. Additionally, evolving market pressures are likely to impact costs for both Zepbound and Wegovy as competition intensifies. 

To navigate the complex implications of these changes effectively, it’s crucial to know the key questions to ask of your PBM, fully evaluate contract options, and assess not only immediate costs but also the long-term impact on employee health outcomes. 

In addition to adopting a holistic approach (opens a new window) to weight health, employers must consider clinical, cost, and market considerations when making informed benefits decisions.  

Lockton’s Pharmacy, (opens a new window) Precision Health (opens a new window), and Clinical (opens a new window) consulting practices can help you align forward-thinking strategies with the unique needs of your organization, balancing cost containment with employee health and well-being — speak to a Lockton expert to learn more.