When we look at the big pharma transactions announced over the last few months, oncology is an obvious hot spot. But right next to it, in terms of strategic importance and deal size, we find a cluster centered on obesity, MASH and metabolic disease. The global “GLP-1 wave” is already a headline topic, yet the recent deals suggest that large pharma is thinking well beyond weight loss alone.
This article is Part 3 of the “Big Pharma Mega Deals in the Last Few Months” series and focuses on this obesity/metabolic cluster. With deals such as Pfizer–Metsera and Roche–89bio in mind, we will explore what the “second act” of the GLP-1 story might look like and how companies are trying to build broader CVRM (Cardiovascular, Renal, Metabolic) franchises.
1. Why treat obesity and metabolic disease as a separate theme?
1-1. From single diseases to “risk clusters”
For a long time, obesity was often framed—sometimes unfairly—as a matter of lifestyle or individual willpower. Today, however, it is increasingly recognized as the hub of a broader risk cluster that includes:
- Type 2 diabetes
- Cardiovascular disease (MI, stroke, heart failure)
- MASH (metabolic dysfunction–associated steatohepatitis)
- CKD (chronic kidney disease)
In this view, obesity is not just one diagnosis among many, but a central organizing node of a multi-organ, multi-risk syndrome. For pharma, this translates into a huge and still expanding opportunity space.
1-2. The limits of a “GLP-1-only” lens
Recent headlines are understandably dominated by GLP-1 and related incretin-based therapies. Yet, if we only look at GLP-1 sales and market share battles, we risk missing the broader structural shift.
- There are domains that GLP-1 alone does not fully address: lipids, hepatic inflammation and fibrosis, residual CV risk, renal decline.
- There is growing interest in agents designed to complement or sequence with GLP-1 rather than compete head-on.
- In the longer term, many companies are clearly aiming at integrated CVRM packages that manage obesity plus its key comorbidities in a coordinated way.
With that in mind, this article focuses less on the GLP-1 wave itself and more on what big pharma is building around and beyond it.
2. Recent obesity/metabolic deals that anchor this discussion
For concreteness, let us highlight two representative transactions from the last few months:
- Pfizer – Metsera: a large transaction aimed at securing a pipeline for obesity and metabolic disease. It should be viewed not as a pure GLP-1 catch-up move, but as part of a broader effort to assemble a differentiated metabolic portfolio.
- Roche – 89bio: a major acquisition centered on the FGF21 analog pegozafermin, with a focus on MASH and lipid/metabolic control, but clear implications for cardiovascular risk as well.
These deals, taken together, help illustrate how pharma is moving from “chasing the GLP-1 leaders” toward building more comprehensive strategies around metabolic risk.
3. Pfizer–Metsera: a “second entry point” for GLP-1 latecomers
3-1. Catching up without simply copying
In the GLP-1 / GIP arena, a few companies have already established strong positions with first- and best-in-class agents. Latecomers cannot expect to win by offering a slightly modified me-too product. Instead, they are exploring:
- Distinct mechanisms or combination profiles that add something meaningful beyond existing GLP-1 therapies
- Specific patient segments where they can demonstrate superior benefit
- Roles in multi-drug regimens that use GLP-1 as a backbone
The Pfizer–Metsera deal can be interpreted as an attempt to build such a differentiated portfolio rather than to replay the first wave of GLP-1 competition.
3-2. Moving toward a “metabolic basket” rather than a single magic bullet
Conceptually, the Metsera pipeline should not be viewed as a search for the one drug that solves obesity on its own. Instead, it reflects the idea of constructing a “metabolic basket” that addresses:
- Weight and glycemic control
- Lipid abnormalities and inflammation
- Cardiovascular and renal risk over the long term
In this context, the strategic question is not “Can we match GLP-1 on weight loss?” but “How can we reshape the overall risk profile of patients when GLP-1 is part of the toolkit?” That is a more complex game—but also one with broader upside.
3-3. Key points from an investor’s perspective
From the viewpoint of investors and BD teams, deals of this kind raise questions such as:
- Which gaps in the incumbents’ GLP-1-centric portfolios are being addressed?
- Is there a credible path to differentiation on hard endpoints such as CV events or renal outcomes?
- How will these assets be positioned in real-world combination and sequence scenarios, and does that positioning make economic sense?
Recent mega deals suggest that large pharma is willing to pay for assets that can improve the long-term risk story in ways that go beyond the initial excitement around weight loss alone.
4. Roche–89bio: connecting MASH, lipids and cardiovascular risk through FGF21
4-1. MASH as more than a liver disease
The Roche–89bio transaction, centered on the FGF21 analog pegozafermin, is about more than “entering the MASH market.” In reality, it speaks to a broader ambition to manage a metabolic syndrome cluster that includes:
- Obesity and insulin resistance
- Dyslipidemia and ectopic fat deposition
- Hepatic inflammation and fibrosis
- Elevated cardiovascular risk
MASH, in this sense, is both a disease entity and a manifestation of deeper systemic metabolic dysfunction. Treating it in isolation would miss much of the long-term value proposition.
4-2. The role of FGF21 analogs and their positioning
FGF21 analogs like pegozafermin offer a multi-faceted profile:
- Improvements in liver fat and fibrosis markers
- Favorable shifts in lipid parameters
- Potential impact on weight and insulin sensitivity
Because their mechanism is distinct from GLP-1, they can be positioned as:
- An option for patients whose risk profile remains suboptimal on GLP-1 alone
- A component of combination strategies that tackle multiple aspects of metabolic dysfunction simultaneously
Seen through this lens, the 89bio acquisition is not merely a bet on a new liver indication; it is part of assembling a toolbox for comprehensive metabolic and cardiovascular risk management.
4-3. CVRM as the organizing framework
Many large pharma organizations now explicitly frame their efforts in terms of CVRM (Cardiovascular, Renal, Metabolic). Within that framework, an asset like pegozafermin can be:
- A key anchor in the emerging MASH space
- A lever to reduce residual cardiovascular risk in high-risk metabolic patients
This CVRM lens makes it easier to see how MASH, obesity, and cardiometabolic risk are being integrated into a single strategic picture, rather than managed as siloed therapeutic areas.
5. What is the “second act” of the GLP-1 story?
5-1. Moving beyond weight loss as the primary competition axis
In the first act of the GLP-1 narrative, competition focused heavily on metrics such as:
- Magnitude of weight loss
- Speed of onset
- Effects on HbA1c and glycemic control
The deals we are now seeing indicate a shift toward a second act in which:
- Reduction in major adverse cardiovascular events
- Prevention or slowing of MASH progression and liver fibrosis
- Protection against CKD progression
become increasingly important differentiation points. This is exactly where complementary mechanisms like FGF21 analogs, dual/triple agonists, and other modalities may come into play.
5-2. Designing for maintenance, not just acute change
Another challenge in obesity and metabolic disease is maintaining benefits over time. Patients may lose substantial weight on therapy, only to regain it after discontinuation. Similarly, improvements in biomarkers may erode if sustained intervention is not feasible.
Against this backdrop, recent deals suggest greater emphasis on:
- Therapies that can be realistically maintained for years rather than months
- Dosing schedules and formulations that fit into daily life
- Risk profiles that allow long-term use without unacceptable trade-offs
In other words, the second act is not only about stronger efficacy, but about building a durable, life-compatible approach to risk reduction.
6. Route of administration and adherence in metabolic disease
6-1. Multiple options: oral, weekly injections, devices and beyond
In obesity and metabolic disease, adherence is tightly linked to the route and frequency of administration. Patients often require treatment over many years, so:
- Daily oral therapies
- Once-weekly or biweekly injectables
- Device-based or patch-like delivery systems
each offer different trade-offs. Recent deals implicitly acknowledge that the “best drug” on paper may not be the best real-world solution if it is too burdensome or inconvenient to use.
6-2. “Implementable innovation” as a critical success factor
From a practical standpoint, innovation in this space must be implementable:
- Side-effect profiles need to be manageable enough for long-term use
- Behavioral and psychological aspects of weight and lifestyle need to be considered
- Therapies must integrate into patients’ work and family lives, not disrupt them
Recent mega deals can therefore be read not only as bets on molecules, but as bets on treatment concepts that could realistically fit into the daily lives of millions of people at risk.
7. How investors and BD teams can interpret obesity/metabolic deals
7-1. Which risk cluster is being targeted?
When evaluating deals in this space, a useful question is: Which part of the risk cluster is this transaction aiming at?
- Is it mainly about obesity plus diabetes?
- Does it extend explicitly into lipids and cardiovascular outcomes?
- Are liver (MASH) and kidney (CKD) endpoints part of the long-term plan?
The broader the cluster, the greater the potential value—but also the greater the complexity and time horizon of development. Many of the recent mega deals seem to be intentionally targeting these broader clusters rather than narrow single-disease slices.
7-2. Standalone competitors vs. combination enablers
Another dimension is whether an asset is primarily intended to:
- Compete head-on as a standalone replacement for existing agents
- Serve as a combination or sequencing partner that enhances the performance of the current standard of care
The latter model, while more complex to study and implement, often maps better to the real-world trajectory of chronic metabolic disease, where patients rarely have a single therapy over their lifetime.
8. Implications for researchers, clinicians and startups
Drawing lessons from recent obesity/metabolic deals, we can highlight a few implications for different groups.
- For researchers: It becomes essential to think in terms of interconnected systems rather than isolated targets—liver, adipose tissue, muscle, heart, vasculature and kidneys all play roles in the metabolic story. Designing interventions that account for these interactions will likely gain importance.
- For clinicians: Clinical practice will increasingly involve constructing individualized CVRM maps for patients—balancing weight, glycemic control, lipids, liver and kidney status, and cardiovascular risk over time, and choosing sequences and combinations accordingly.
- For startups: The key question is less “Can we build the next blockbuster obesity drug?” and more “Where in the broader CVRM portfolio can we create unique value?” Being able to clearly articulate which part of the risk cluster is being addressed, and how that fits into a larger pharma partner’s strategy, will be crucial.
9. My thoughts and future outlook
Looking across the recent obesity and metabolic deals, it feels clear that we have moved beyond a phase where the central story is simply “new weight-loss drugs.” The capital and attention are now flowing toward a deeper goal: reshaping long-term cardiovascular, hepatic and renal risk in a large and vulnerable population. In that sense, the GLP-1 wave may be best understood as a starting point—a catalyst that has forced health systems, payors and companies to reconsider how they think about metabolic risk as a whole.
For patients living with obesity and metabolic disease, however, the experience is not primarily about curves on a Kaplan–Meier plot. It is about whether they can go to work without constant fatigue, whether they feel comfortable joining family events, whether they can manage treatment without turning their entire life inside out. As developers and investors, it is easy to focus on biomarkers and event rates, but the question that ultimately matters is: what kind of life does this therapeutic strategy make possible in practice? My hope is that as the field moves into this second act, we will see more solutions that are not only powerful on paper, but also realistic companions for people over the many years that metabolic risk unfolds. If this article helps readers think a bit more in that direction, then it has done its job.
This article was prepared by the Morningglorysciences editorial team.
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