The readout of the Wegovy SELECT cardiovascular outcomes trial marks a moment of truth for the future of the obesity market – and SELECT did deliver.

Ultimately, health systems attribute value to improved cardiovascular outcomes, not weight loss on its own. Therefore, demonstrating that weight management translates into a reduction in cardiovascular events – and thus saves lives – is crucial to convince payers to expand reimbursement and access for anti-obesity pharmacotherapies and for healthcare professionals to change clinical practice, including treatment to specific weight loss targets.

Novo’s SELECT trial investigated the impact of Wegovy-induced weight loss on the risk of having cardiovascular events in overweight or obese patients without diabetes. Its primary endpoint was time to first occurrence of a composite endpoint consisting of cardiovascular death, non-fatal myocardial infarction, or non-fatal stroke (MACE-3). The now reported, statistically significant 20% reduction in MACE-3 events vs. placebo must be considered a major success, with all three components of the primary endpoint contributing to the superior MACE reduction. It also exceeds expectations of many analysts and investors, who were hoping to see 15-17% reduction in eager anticipation of the actual trial results.

The positive SELECT readout has far-reaching implications which fundamentally manifest themselves in two ways:

• Wegovy: As the only anti-obesity therapy supported by cardiovascular outcomes data, Wegovy is now highly differentiated and can make a specific, compelling and evidence-backed case to payers for broad coverage and access. This matters because it shifts the debate, and the basis of competition, towards cardiovascular outcomes, away from a singular focus on headline weight reduction, a dimension on which Wegovy no longer stands out. Notwithstanding the common off-label use of Ozempic and Mounjaro, Wegovy is currently the only drug among the new generation of highly potent anti-obesity treatments specifically approved for this condition. However, formidable future competitors are looming and closing in fast.
  
  Lilly’s fast follower, dual GLP-1/GIP receptor agonist Mounjaro, expected to be approved by the FDA as obesity treatment later in 2023, has outperformed Wegovy, and Ozempic, in weight loss achieved in both overweight and obese patients without diabetes and in the more difficult to treat population of diabetic patients who are also overweight or obese. Meanwhile, Lilly’s triple GLP-1/GIP/glucagon receptor agonist retatrutide set a new record in a recent phase 2 trial, helping patients lose an average of 24% of their weight after 48 weeks, while incremental weight loss hasn’t plateaued at that time point. Furthermore, two oral GLP-1 receptor agonists, Pfizer’s danuglipron and Lilly’s orforglipron, have shown comparable weight loss to Wegovy while offering the convenience of a pill. These examples clearly illustrate the emergence of a fiercely competitive obesity treatment landscape.
  
  Crucially, however, none of those competitors will have any cardiovascular outcomes data of their own for some years to come. Even the most advanced cardiovascular outcomes trial in obesity, Lilly’s SURMOUNT-MMO assessing Mounjaro, is not expected to read out until Q4/2027. While Lilly’s other cardiovascular outcomes trial underway, SURPASS-CVOT, is expected to read out sooner, in Q4/2024, it investigates Mounjaro in T2D patients against Trulicity, and thus its outcomes data are likely to be more difficult to compare directly to Wegovy’s SELECT.
  
  The pressure is clearly on for Novo’s competitors to follow suit with their own cardiovascular outcomes data. Wegovy may face the risk of ‘benefit extrapolation’ to other anti-obesity drugs as key healthcare stakeholder take note of SELECT. But with Wegovy’s data advantage set to last for a few years, it is within Novo’s hands to press home this advantage via promotional and medical affairs engagement to defend Wegovy’s market leadership position and boost its performance in the near term. Seizing this momentous opportunity, however, will now depend on ramping up supply to meet relentlessly surging patient demand.


• Obesity market: By implication, SELECT will have a beneficial halo effect across the obesity market and act as a catalyst for its rapid expansion. Firstly, the positive cardiovascular outcomes demonstrated in SELECT establish the missing link between weight management and ultimately saving lives. Secondly, this translates into substantial cost-offsets for stretched health systems from medication-assisted weight loss by avoiding downstream complications from obesity-related comorbidities.
  
  These compelling benefits bolster the case for payers to re-visit the value of anti-obesity therapies in general and expand coverage and access for such treatments. Specifically in the U.S., SELECT will add impetus to efforts like the Treat and Reduce Obesity Act of 2021, which seek to lift the statutes prohibiting Medicare coverage of anti-obesity drugs.
  
  Furthermore, SELECT will drive a change in clinical practice and prompt updates of treatment guidelines to specify weight management targets, formalise the role of pharmacotherapies in treating obesity and help improve diagnosis and treatment rates from historical lows.

The positive readout of the SELECT cardiovascular outcomes trial represents a major inflection point in the expansion of the obesity market and sets it on a trajectory to reach a size of possibly many tens of billions of dollars globally.

To learn more about the obesity opportunity, please read our obesity deep dive, part of our recent white paper on the broader renaissance of cardiometabolic innovation. Download our white paper here: https://www.iqvia.com/library/white-papers/a-renaissance-for-cardiometabolic-innovation