In this blog we will discuss the implications of recommendations stipulated by these two sets of guidance for the obesity market and innovators developing new AOMs.

Implications for the obesity market

When looking at the impact of the recently published guidance, it is important to distinguish between the private and reimbursed markets for AOMs, which have fundamentally different dynamics and drivers.

Private market

The direct impact of the Lancet Commission’s recommendations will be minimal for the private market.

Most self-paying, private patients are predominantly motivated by weight loss, who, as consumers, are unlikely to pay much attention to the clinical reframing of obesity as pre-obesity vs. clinical obesity, or the subtleties of the proposed new diagnostic criteria.

As health systems are concerned about the budget impact of reimbursing AOMs, they are unlikely to impose stricter diagnostic or eligibility criteria on the private market, because self-paying patients help alleviate funding pressures. Therefore, BMI will continue to be the principal measure for assessing obesity in this market.

Consumer choice in the private market is driven by weight loss delivered, price, brand name recognition, mode of administration, and long-term tolerability and safety, while wider benefits on co-morbidities typically do not feature as an important consideration – none of these will be impacted by the Lancet Commission’s recommendations.

However, there will be an indirect impact on the private market from defining clinical obesity based on functional impact, if health systems were to adopt the Lancet Commission’s recommendations in the reimbursed market.

For new entrants, this would translate into a higher evidence bar to clear for reimbursement, as they will need to demonstrate functional and possibly outcomes benefits of new AOMs. Additionally, if the draft FDA guidance was to be implemented, it would require innovators to run more complex clinical trials for new AOMs to secure regulatory approval. Since innovators will typically only run one programme for generating evidence to support their AOMs in both the private and reimbursed markets, it will be defined by the stricter requirements for the latter.

Reimbursed market

The Lancet Commission’s recommendations will likely have modest impact on the reimbursed market.

The Commission’s definition of clinical obesity, and making this population the main focus for AOM use, broadly aligns with how publicly funded health systems already think about prioritising AOM reimbursement, e.g., NICE guidance defining eligibility for treatment with semaglutide and tirzepatide using a BMI cut-off plus presence of a co-morbidity, or Medicare Part D coverage of AOMs with medically accepted indications, such as diabetes or reducing the risk of major adverse cardiovascular events in patients with established cardiovascular disease.

Therefore, application of the proposed diagnostic criteria for clinical obesity will not materially change eligibility for reimbursed treatment with AOMs, as most overweight and obese people have one or more co-morbidities that equate to functional impact as a result of excess adiposity. For example, IQVIA data shows that 75% of U.S. patients with BMI 27-29.9 (overweight) have one or more co-morbidities, while this increases to over 80% for patients with BMI >35 (see Figure 2).

Furthermore, as we are at the very beginning of treating obesity with effective pharmacological interventions, with only a small percentage of the overall obese population being treated with AOMs to date, the proposed diagnostic criteria will not impose any meaningful ceiling on the AOM market that would limit its potential.

However, the Lancet Commission’s recommendations help reinforce payer-driven eligibility criteria for prioritising AOM treatment and provide some clinical legitimacy. In turn, this has implications for evidence requirements for securing AOM reimbursement, e.g., the likely need for demonstrating functional and possibly outcomes benefits in obese patients.

On the positive side, by defining clinical obesity as a legitimate, standalone disease that needs to be treated, the Lancet Commission strengthens the case for reimbursement of AOMs for this population. This increases the pressure on payers and policy makers to abandon the argument that AOMs are lifestyle drugs, which is often used to justify not covering these therapies, for example, in several European countries.

The adoption and practical application of the Lancet Commission’s recommendations by health systems is not a forgone conclusion, however. Even seemingly straightforward measures like waist circumference are fraught with practical challenges, e.g., ensuring accuracy, and are not routinely captured, whereas the wide use of sophisticated diagnostic approaches, such as DEXA scans to analyse body composition and distribution of fat and muscle, face infrastructure and capacity limitations.

As health systems continue to be under significant financial and operational pressure, it is entirely possible that the need for pragmatism prevails, with the continued use of ‘BMI plus one or more co-morbidities’ as a good enough rule of thumb, especially in the primary care setting.

Finally, by deprioritising pre-obesity and focusing on clinical obesity for AOM treatment, the Lancet Commission disregards the benefits of early intervention with AOMs to lower the risk of patients with pre-obesity progressing to clinical obesity, and thus avoiding downstream complications. Apart from ethical implications, especially for younger patients, this will likely be a point of contention with innovators, e.g., Novo Nordisk established the Transformational Prevention Unit with a mission to increase obesity-free life years, via targeted interventions, which may include pharmacotherapies [3], aimed at high-risk individuals to prevent them from developing obesity in the first place.

Implications for obesity innovators

The impact on obesity innovators of the Lancet Commission’s recommendations and the FDA draft guidance will be profound.

Innovators developing new AOMs will have to clear a higher evidence bar for both regulatory approval and securing reimbursement and access:

• Recruitment: Inclusion/exclusion criteria for trial recruitment will need to evolve to ensure trials reflect the age, sex, race and ethnicity of obese patients in clinical practice for the U.S. population. Furthermore, applying the obesity definition and diagnostic recommendations from the Lancet Commission would result in additional criteria, e.g., characterising the severity of obesity beyond BMI.
• Endpoints: Draft FDA guidance recommends monitoring body composition for a subset of patients, to assess the quality of weight loss (fat vs. lean mass) in addition to overall weight loss achieved. Furthermore, to demonstrate efficacy in the context of the Lancet Commission’s definition of clinical obesity based on the functional impact of excess adiposity, different endpoints are needed that assess functional benefits of AOMs, including impact on weight-related co-morbidities.
• Trial size: Draft FDA guidance maintains the required size of safety trials, with a minimum of 4,500 patients across active and placebo arms.

As a result, clinical development of new AOMs will become more expensive and operationally more challenging, e.g., exacerbating the already intense competition for obese patients during trial recruitment, while more onerous inclusion/exclusion criteria will make finding eligible patients even harder.

Moreover, indication expansion is elevated beyond a nice-to-have, with the need to explore the impact on co-morbidities at earlier stages in the development lifecycle, because relying on superior weight loss alone as differentiator for efficacy will no longer be sufficient for the reimbursed market.

Big pharma companies have a structural advantage to weather this storm, e.g., their deep pockets and large-scale clinical operations, enabling them to run more complex or larger trials and support broad development programmes to pursue multiple labels, including different co-morbidities.

Incumbents Novo Nordisk and Lilly are particularly well placed to entrench their leading position at the expense of future competitors. For example, they have already expanded the labels for their respective flagship assets semaglutide and tirzepatide, with further indications to be added, and have, or are generating, data on functional benefits and even cardiovascular outcomes (see Figure 3).

Given their head start as incumbents, both companies have a strong incentive to insist that wider benefits in co-morbidities are not considered a class effect, and instead are a key requirement any bona fide AOM must demonstrate.

Conversely, the Lancet Commission’s recommendations and the FDA draft guidance could pose challenges for emerging biopharma companies (EBPs). EBPs typically have tight budgets, and may have pursued development strategies aimed at differentiation on superior weight loss alone, which makes them vulnerable. They will struggle to fund or navigate the more complex clinical development of AOMs, including exploring functional benefits early on, with impact on co-morbidities, to differentiate their assets, including as attractive targets for potential acquisitions or partnerships. Of course, this guidance is currently at draft stage, and therefore open to response and amendment. With a new head of the FDA due to start from a new administration, much is currently uncertain.

Consequently, we may see the emergence of a buyer’s market in obesity dealmaking, where larger players will be able to cherry pick the best assets once supported by sufficient data, because the cost of late-stage clinical development for AOMs, and by extension self-commercialisation, could be increasingly prohibitive for EBPs under the new guidance.

It is possible that China may follow a different path, for example, by encouraging approval of domestically developed AOMs, an area with many active Chinese companies, and potentially applying different evidence requirements, which would translate into different clinical trial specifications.

These AOMs originating from and approved in China could subsequently expand into LMICs, assuming local regulatory requirements do not mirror FDA guidance. The AOM market in those countries can be expected to remain predominantly out-of-pocket, which limits the impact of the Lancet Commission’s recommendations in LMICs, including on evidence requirements, for the reasons discussed earlier.

Final thoughts

The implications discussed in this blog are based on a scenario where both sets of guidance have been adopted and implemented as recently published.

However, a number of uncertainties and questions remain:

• Will health systems, and practicing physicians, challenge the practicality of the Lancet Commission’s recommendations?
• Following the consultation period, what amendments may be incorporated as the FDA draft guidance is finalised?
• Could we see a convergence of guidance, where key recommendations by the Lancet Commission are incorporated into the FDA guidance on clinical trials, e.g., on endpoints, or characterising trial populations?
• When and how will the EMA evolve its guidelines for obesity trials [4], which were last revised in 2016, as another major regulator for an important obesity market?
• Could we see a separation of clinical development paths for the private vs. reimbursed markets, or in the U.S./Europe vs. China, given the difference in evidence requirements? For example, an innovator may choose to focus on the private market only to clear a lower evidence bar.
• How will innovators utilise RWE to address more stringent evidence requirements, e.g., demonstrating functional benefit and impact on co-morbidities, or long-term safety? For example, a recently published large, retrospective real-world study highlights the potential of RWE, notwithstanding its limitations in patient demographics. Using data from the U.S. Department of Veteran Affairs on 2 million diabetes patients, the study showed reduced risks of 42 conditions in GLP-1 users [5].

The obesity market remains in flux, and innovators must therefore stay alert to the moving goal posts to ensure they don’t find themselves pursuing an obsolete strategy.

References

1. F. Rubino et al., Definition and diagnostic criteria of clinical obesity, The Lancet Diabetes & Endocrinology, 14 January 2025; https://doi.org/10.1016/S2213-8587(24)00316-4
2. FDA: Developing drugs and biological products for weight reduction; draft guidance for industry, January 2025: https://www.fda.gov/media/71252/download
3. Novo Nordisk, Transformational Prevention Unit: https://www.novonordisk.com/partnering-and-open-innovation/transformational-prevention-unit.html
4. EMA, 2016: Guideline on clinical evaluation of medicinal products used in weight management
5. Xie, Y., Choi, T. & Al-Aly, Z. Mapping the effectiveness and risks of GLP-1 receptor agonists. Nat Med (2025). https://doi.org/10.1038/s41591-024-03412-w