The GLP-1 drug class has transformed the pharmaceutical landscape, with Novo Nordisk and Eli Lilly leading a market projected to exceed $470 billion by 2030. But as the next generation of obesity therapies enters clinical trials, and as new players like Amgen join the race, a critical question is emerging: Are we measuring the right outcomes to support long-term value and regulatory clarity?
Rethinking the Definition of Obesity
The chronic disease of Obesity is not about excess weight. According to the World Health Organization’s (WHO) International Disease Classification Index (ICD-11), it is defined as abnormal or excessive fat accumulation that impairs health. This impairment is driven by:
- Metabolic dysfunction (e.g., insulin resistance, dyslipidemia)
- Chronic inflammation
- Hormonal imbalance
- Ectopic fat deposition (e.g., in the liver, heart, and pancreas)
What If Biomarkers Were Primary Endpoints?
“If we measured GLP-1 therapies by metabolic health, not just weight loss, the investment story would look very different.”
If trials had been designed around biomarkers of metabolic health, rather than weight alone, the outcome could have been very different:
- Regulatory approvals might have been broader and faster, encompassing indications like metabolic syndrome, NAFLD/NASH, or cardiovascular risk reduction.
- Investor confidence could have been more stable, grounded in a portfolio of health outcomes rather than a single metric.
- Market differentiation would be clearer, especially for next-generation entrants like Amgen, whose MariTide program shows promise in long-acting hormonal modulation.
ECO 2025: A Turning Point?
At the European Congress on Obesity (ECO 2025), several presentations challenged the weight-centric model:
- A Novo Nordisk symposium emphasized proteomic footprints and systemic health improvements from GLP-1s.
- A poster by Luca Busetto proposed a treat-to-target model integrating biomarkers and adiposity measures to reduce risk of T2D and ASCVD.
- A secondary analysis of the SELECT trial showed early cardiovascular benefits from semaglutide, even before significant weight loss.
These findings suggest that biomarkers like CRP, triglycerides, and liver fat may be more predictive of long-term outcomes than BMI.
“Biomarkers like inflammation, insulin sensitivity, and liver fat are better predictors of long-term outcomes than BMI alone.”
Hormonal Complexity and Market Confusion
Investor reactions have often lagged behind the science. Confusion around hormonal mechanisms, GLP-1 vs. GIP vs. glucagon, has led to misinterpretation of trial data and share price volatility.
For example:
- Semaglutide (Novo) targets GLP-1.
- Tirzepatide (Lilly) targets GLP-1 and GIP.
- MariTide (Amgen) explores GLP-1 and glucagon pathways.
Lessons from the Novo-Lilly Rivalry
Lilly’s rise wasn’t just about weight loss. It was about trial design, regulatory strategy, and a broader view of therapeutic value. Novo has responded with next-gen programs, but the key takeaway is this: companies that understand and communicate the full metabolic impact of their therapies are better positioned to lead.
The key takeaway is this: companies that understand and communicate the full metabolic impact of their therapies are better positioned to lead.
What the EMA and Investors Should Be Watching
As the field matures, both regulators and investors should consider:
- Biomarker data: Inflammation, lipid shifts, and liver fat reduction are leading indicators of value.
- Trial design evolution: New studies reflect a more nuanced understanding of obesity.
- Regulatory signals: The EMA may be well-positioned to lead in recognizing metabolic endpoints beyond BMI.
- Pipeline differentiation: Understanding hormonal targets is essential for assessing competitive positioning.
Reframing the Narrative
The GLP-1 era has already reshaped obesity treatment. But if we want to avoid future shocks and unlock the full potential of these therapies, we need to start talking about obesity the way the science does. That means focusing on metabolic health, not just weight loss. For investors, that shift in perspective is strategic. For regulators, it may be essential.
Conclusion: A Smarter Path Forward
As the GLP-1 class continues to evolve, both the investment community and regulatory bodies have an opportunity, and a responsibility, to rethink how success is measured.
Obesity is not a matter of weight; it is a complex, chronic disease rooted in metabolic dysfunction. The drugs now emerging are capable of addressing that dysfunction in ways that go far beyond the scale.
By shifting focus toward validated biomarkers such as inflammation, insulin sensitivity, and liver fat, we can better capture the true therapeutic value of these treatments. This reframing would not only support more stable and informed investment decisions, but also enable regulators like the EMA to approve therapies based on outcomes that matter most for long-term health.
“The next phase of the GLP-1 story will be shaped not just by innovation, but by how we choose to measure success.”
The next phase of the GLP-1 story will be shaped not just by innovation in the lab, but by how we choose to measure and communicate success. It’s time to align the science, the markets, and the regulatory frameworks with the full reality of what these therapies can do.