Could the next healthcare breakthrough happen outside the lab?
Scientific innovation is transforming how we treat disease, but the next true breakthrough won’t happen in a lab alone.
Beyond the scale: why the next breakthrough in cardiometabolic care may not be more weight loss
What if the biggest challenge facing the next generation of cardiometabolic medicines isn't achieving better outcomes, but deciding what “better” actually means?
For the first wave of GLP-1s, weight loss gave us a powerful answer. The number on the scale was a simple, visible measure of progress, and the results transformed expectations of what treatment could achieve.
But weight loss only tells us part of the story. Cardiometabolic health encompasses a much wider set of outcomes, and progress in one doesn’t necessarily mean progress in another. The outcome that matters most for one patient today may be different for another, or even for that same patient several years from now.
“Better” is becoming a moving target.
New measurements of progress
Yesterday’s breakthroughs have a habit of becoming tomorrow’s baseline, and that’s certainly true of GLP-1s. As efficacy rises, meaningful weight loss is just the entry price for the next generation of cardiometabolic medicines. That opens up a much bigger question: what does “better” look like from here?
A 2026 analysis of the SELECT trial (Semaglutide Effects on Cardiovascular Outcomes in People with Overweight or Obesity) found that semaglutide’s cardiovascular benefit could not be fully explained by changes in weight, waist circumference or other measured cardiovascular risk factors. The conclusion? According to a SELECT study lead, “Semaglutide should be considered as a cardiovascular disease reduction drug and not just as a weight loss drug.” [1,2]
The outcomes question expands, then, from “how much weight?” to “what does better health require?”
The liver disease, MASH (metabolic dysfunction-associated steatohepatitis), makes this even more tangible: recent FGF21 studies have demonstrated improvements in MASH and fibrosis even when weight change was not significantly different from placebo – showing that meaningful disease progress can’t always be measured on the scale [3].
These are important signals. Because if improvements in cardiometabolic health aren’t always reflected in pounds and kilos lost, weight becomes one dimension of progress rather than a proxy for the whole. The outcomes question expands, then, from “how much weight?” to “what does better health require?”
And the dimensions that matter depend on where you look.
For someone living with obesity, meaningful and durable weight loss and reducing downstream risk may remain central goals. In prediabetes, preventing or delaying progression to type 2 diabetes becomes important, so too addressing broader metabolic and cardiovascular risk. For someone with established T2D, the picture expands to include glycaemic control, weight, cardiovascular and kidney outcomes [4]. In MASH with clinically significant fibrosis, weight loss alone may not define success – MASH resolution and fibrosis improvement become distinct objectives. And with cardiovascular disease, heart failure or CKD, organ protection and event reduction can become priorities beyond weight or glycaemic improvement alone.
These needs can also coexist. Cardiometabolic disease doesn’t follow a neat sequence. Obesity and metabolic risk can sit alongside T2D, MASH, cardiovascular or kidney disease. Different aspects can emerge, improve or progress at different rates. And as a person’s health changes, so can the outcomes that matter most to them.
Which means the definition of “better” is multidimensional and dynamic: it moves with the patient.
No single answer
The science is evolving too. Pipelines are expanding across incretins, amylins, combinations, oral therapies, muscle-preserving approaches and organ-directed mechanisms [5,6]. With that diversity, the basis of competition is broadening beyond how much weight is lost to encompass more dimensions of value: efficacy, durability, glycaemic control, tolerability, convenience, body composition, cardiovascular outcomes and organ health. The reality? No single medicine will have all the answers for every patient.
Cardiometabolic disease is complex and evolving. Our therapeutic options are too. And that could change the way the category thinks about progress.
The emerging pipeline reflects a future in which different mechanisms and modalities could play different roles, addressing different outcomes for different people at different moments. Cardiometabolic disease is complex and evolving. Our therapeutic options are too. And that could change the way the category thinks about progress.
Choice becomes the challenge
As therapeutic choice expands, navigating it becomes more complex. The best option will depend on what matters most to each patient, and how that changes as their needs evolve. That means thinking differently about the treatment path, recognising that what matters at the beginning of someone’s cardiometabolic journey may not be what matters later. It means looking across interconnected health rather than viewing obesity, diabetes, liver, cardiovascular and kidney disease entirely in isolation. And it means seeing progress through multiple dimensions rather than relying on one dominant measure.
Pharma has already responded, with pipelines looking beyond obesity to find different answers across an evolving cardiometabolic continuum.
Leading what comes next
This could change what it means to lead the category. As efficacy rises, therapeutic choice expands and the definition of “better” becomes more nuanced, leadership may increasingly be shaped by a series of shifts. From best product to best treatment path. From maximum weight loss to multidimensional progress. From single disease to interconnected health. From portfolio breadth to portfolio purpose. From winning the start to being ready for what comes next.
The first wave of GLP-1 innovation transformed expectations around how much weight people could lose. The next wave has the potential to expand our understanding of what cardiometabolic treatment can achieve.
As obesity, diabetes, MASH, cardiovascular and kidney disease are increasingly understood as interconnected but distinct manifestations of cardiometabolic dysfunction, the next generation of care must reflect the dynamic nature of the category. No single measure, mechanism or treatment is likely to define better health for every patient. What matters most depends on the disease, the individual and the moment.
Perhaps that’s where the next opportunity for category leadership lies: in understanding the many different things “better” can mean, and building portfolios capable of responding as that answer changes.
References
[1]. European Society of Cardiology. Weight loss alone does not explain lower heart disease for those on semaglutide. 24 September 2026
[2]. Colhoun HM, et al. Semaglutide and cardiovascular risk reduction: a mediation analysis of the SELECT trial. European Heart Journal. 2026. doi: 10.1093/eurheartj/ehag524.
[3]. Stefan N, Targher G. Pharmacological treatment of MASH. Diabetologia. 2026;69:3148–3161. doi:10.1007/s00125-026-06796-1.
[4]. American Diabetes Association Professional Practice Committee. Standards of Care in Diabetes—2026. Diabetes Care. 2026;49(Suppl 1)
[5]. Reuters. Experimental Lilly combination drug tops Zepbound in weight-loss trial. 30 September 2026.
[6]. Reuters. Regeneron drug halves muscle loss in combination with Novo’s semaglutide in trial. 30 September 2026.
