Assessing Novo Nordisk’s Competitive Edge in the GLP-1 Weight-Loss Market

The GLP-1 receptor agonist market has become a battleground for pharmaceutical giants, with Novo Nordisk’s Wegovy (semaglutide) and Eli Lilly’s Zepbound (tirzepatide) leading the charge. While both drugs target obesity—a condition intricately linked to cardiovascular disease (CVD)—their distinct mechanisms and clinical outcomes position them differently in the competitive landscape. For investors, understanding the strategic implications of Wegovy’s cardiovascular efficacy versus Zepbound’s weight-loss superiority is critical to evaluating Novo Nordisk’s long-term market dominance.

Weight Loss Efficacy: Zepbound’s Edge

Zepbound has consistently outperformed Wegovy in weight reduction metrics. In the SURMOUNT-5 trial, tirzepatide achieved a 20.2% average body weight loss over 72 weeks, compared to Wegovy’s 13.7% [1]. This 47% relative advantage is attributed to Zepbound’s dual activation of GLP-1 and GIP receptors, enhancing satiety and metabolic regulation [3]. Additionally, 31.6% of Zepbound users achieved ≥25% weight loss, versus 16.1% for Wegovy [1]. These results have positioned Zepbound as the gold standard for maximal weight reduction, particularly in patients prioritizing rapid, substantial outcomes.

However, real-world data paints a nuanced picture. A meta-analysis of randomized controlled trials and retrospective cohorts found that Zepbound’s weight loss benefits were dose- and duration-dependent, with real-world adherence often lagging behind trial conditions [2]. This raises questions about long-term sustainability, a factor investors must weigh against clinical trial optimism.

Cardiovascular Outcomes: Wegovy’s Strategic Strength

While Zepbound excels in weight loss, Wegovy’s cardiovascular benefits are unmatched. The SELECT trial demonstrated that semaglutide reduced major adverse cardiovascular events (MACE)—including heart attack, stroke, and cardiovascular death—by 20% compared to placebo in patients with obesity and preexisting CVD [4]. This advantage was further validated in the STEER real-world study, which reported a 57% greater risk reduction for cardiovascular events with Wegovy versus Zepbound in patients with obesity and established CVD [2]. Specifically, Wegovy recorded 15 cardiovascular events (0.1%) versus 39 (0.4%) for Zepbound over 3.8 months of follow-up [2].

This cardiovascular efficacy is a critical differentiator. Obesity is a leading modifiable risk factor for CVD, and Wegovy’s ability to reduce MACE independently of weight loss magnitude—observed in SELECT—positions it as a first-line therapy for patients with comorbid CVD [4]. For Novo Nordisk, this translates to a unique value proposition: a drug that addresses both obesity and its most severe complications.

Strategic Implications for Novo Nordisk

The dichotomy between weight loss and cardiovascular outcomes creates a strategic inflection point for Novo Nordisk. While Zepbound’s superior weight loss may attract patients seeking maximal body mass reduction, Wegovy’s cardiovascular benefits cater to a high-priority demographic: individuals with obesity and existing CVD. Given that CVD accounts for ~30% of global deaths annually [5], Wegovy’s ability to mitigate this risk could drive adoption in clinical guidelines and formulary decisions.

Moreover, Wegovy’s cardiovascular advantages align with Novo Nordisk’s broader mission to combat chronic diseases. The company’s investment in the SELECT trial—a landmark study involving 17,604 patients—has generated robust evidence to support regulatory approvals and payer negotiations. This contrasts with Zepbound, which, despite superior weight loss, lacks comparable cardiovascular data [4].

Real-World Performance and Market Dynamics

Real-world outcomes, however, temper the clinical trial optimism. Both drugs show reduced efficacy in practice, with Wegovy achieving 8.7% average weight loss at one year versus 9.4% in trials [3]. For Zepbound, real-world adherence gaps further dilute its edge. Yet, Wegovy’s cardiovascular benefits remain consistent, as evidenced by STEER’s real-world risk reduction [2]. This resilience in real-world settings strengthens Novo Nordisk’s competitive position, as payers increasingly prioritize therapies with proven clinical outcomes.

Conclusion: A Dual-Pronged Investment Thesis

Novo Nordisk’s competitive edge lies in Wegovy’s dual role as a weight-loss and cardiovascular therapy. While Zepbound’s weight loss efficacy is compelling, Wegovy’s cardiovascular benefits address a larger unmet need, particularly in aging populations with comorbid CVD. For investors, this positions Novo Nordisk to dominate the GLP-1 market in two ways: (1) by capturing the CVD-focused segment with Wegovy and (2) by leveraging Zepbound’s weight loss leadership to expand into broader obesity markets.

As the obesity-CVD nexus intensifies, Wegovy’s cardiovascular efficacy will likely remain a cornerstone of Novo Nordisk’s growth strategy, offering a durable moat in an increasingly crowded therapeutic landscape.

Source:
[1] Lilly's Zepbound® (tirzepatide) superior to Wegovy® [https://investor.lilly.com/news-releases/news-release-details/lillys-zepboundr-tirzepatide-superior-wegovyr-semaglutide-head]
[2] Comparative Efficacy of Tirzepatide vs. Semaglutide in [https://pmc.ncbi.nlm.nih.gov/articles/PMC12151102/]
[3] Zepbound outduels Wegovy in weight-loss clinical trial [https://news.cornell.edu/stories/2025/05/zepbound-outduels-wegovy-weight-loss-clinical-trial]
[4] Semaglutide and Cardiovascular Outcomes in Obesity without Diabetes [https://pubmed.ncbi.nlm.nih.gov/37952131/]
[5] Novo Nordisk's Wegovy® cuts risk of heart attack, stroke or death by 57% compared to tirzepatide in real-world study of people with obesity and cardiovascular disease [https://www.prnewswire.com/news-releases/novo-nordisks-wegovy-cuts-risk-of-heart-attack-stroke-or-death-by-57-compared-to-tirzepatide-in-real-world-study-of-people-with-obesity-and-cardiovascular-disease-302542590.html]