What are the key players in the pharmaceutical industry targeting GLP-1?

Introduction to GLP-1

Definition and Biological Role
Glucagon-like peptide-1 (GLP-1) is a hormone produced by intestinal L-cells in response to nutrient ingestion. It plays a critical role in glucose homeostasis by stimulating insulin secretion in a glucose-dependent manner, inhibiting glucagon release, slowing gastric emptying, and promoting satiety. These actions help to lower postprandial blood glucose levels and also contribute to weight loss. GLP-1 is rapidly degraded by dipeptidyl peptidase-4 (DPP-4), which has driven extensive research into making it therapeutically useful by either developing DPP-4‑resistant analogs or by utilizing DPP‑4 inhibitors to prolong its action. The hormone not only has a direct impact on the pancreatic β-cells but also exerts various effects in the brain, cardiovascular system, and other peripheral tissues, thereby influencing energy balance, cardiovascular health, and even neuroprotection.

Importance in Pharmaceutical Research
Due to its pleiotropic effects, GLP-1 has emerged as a promising target in the treatment of type 2 diabetes mellitus (T2DM) and obesity. The interest in GLP-1–based therapies has spurred the development of several molecules including short‑acting and long‑acting peptide mimetics, as well as nonpeptidic small-molecule agonists. Pharmaceutical research has expanded the scope of GLP-1 beyond glycemic control to explore its cardiovascular and neuroprotective benefits, leading to diversified clinical indications. This hormone’s unique glucose-dependent action minimizes the risk of hypoglycemia compared with other insulin secretagogues, making it a highly attractive candidate for innovative therapeutic strategies. Furthermore, the need to overcome its short half‑life due to rapid enzymatic degradation has spurred technological advances such as microsphere formulations, albumin-binding strategies, and even novel oral delivery systems.

Major Pharmaceutical Companies Targeting GLP-1

Leading Companies
The two standouts in the GLP-1 landscape are Eli Lilly and Novo Nordisk. These companies have taken a leading role through aggressive research and robust commercial strategies:

• Eli Lilly has achieved significant market prominence with products such as Mounjaro and the emerging orforglipron candidate. The company’s focus is not only on injectable formulations but also on exploring small-molecule oral formulations to improve patient compliance and expand market reach. Their strong pipeline, advanced clinical trial data, and global commercialization efforts have made them a dominant force in the GLP-1 space.

• Novo Nordisk is renowned for its innovations with drugs like Ozempic and Wegovy. The company’s ability to develop once-weekly injectable products with optimized pharmacokinetic profiles has allowed it to capture a major share of the GLP-1 market, particularly in indications related to both type 2 diabetes and obesity. Novo Nordisk’s integrated approach—for example, leveraging its expertise in peptide drug stability and delivery—is a core reason for its sustained dominance in this field.

Additionally, these companies have been strategically using their patents, regulatory exclusivities, and technological advancements to protect their market share. For instance, detailed analyses have shown that these giants use robust intellectual property portfolios that include patents not only on the active molecule but also on delivery mechanisms and formulation technologies, thereby extending their revenue horizons and deterring generic competition.

Emerging Players
While Eli Lilly and Novo Nordisk currently represent the duopoly in the GLP‑1 market, several emerging players are also making noteworthy contributions:

• Terns Pharmaceuticals is an example of an emerging company that has recently advanced its oral small-molecule GLP-1 receptor agonist candidate, TERN‑601, through early phase clinical trials. Their development programs suggest potential breakthroughs in oral delivery methods that might transform the landscape by offering alternatives to injections.

• Carmot Therapeutics is another emergent player targeting diabetes with injectable GLP‑1 drug candidates. Reports indicate that the firm is considering an initial public offering (IPO) or a buyout at valuations exceeding US$1 billion, based on its Stage II pipeline. Their focus spans type 1 and type 2 diabetes, emphasizing a broader application of GLP‑1–directed therapies.

• Oramed Pharmaceuticals has also entered the sphere by developing oral formulations of GLP‑1 analogs. Their preclinical and early clinical trials have demonstrated that when GLP‑1 analogs are combined with absorption enhancers, they can be successfully delivered via the gastrointestinal tract while retaining biological activity. This innovative approach is gaining traction and could open new avenues for non‑parenteral administration.

• Other companies, such as AULBIO, are exploring novel formulations of GLP‑1-based therapeutics that show improved dissolution characteristics and bioavailability through innovative microsphere encapsulation and first carrier technologies. These efforts underscore the broader industry interest in optimizing drug delivery and patient outcomes.

• In addition, Altimmune, Hanmi Pharmaceutical, and certain divisions of multinational corporations like Amgen and Pfizer are engaged in the development of agents targeting the GLP‑1 receptor, either as monotherapy or in combination with other incretin modulators (e.g., GIP). For instance, Amgen has been exploring innovative GLP‑1 receptor agonist and GIP antagonist antibody programs, reflecting the diversification in the class. Similarly, Pfizer has taken steps in the small‑molecule arena, joining the race with promising early‑phase clinical findings.

Strategies and Developments

Drug Development Strategies
Pharmaceutical companies have pursued multiple avenues of research to overcome the inherent challenges posed by GLP‑1’s pharmacokinetic limitations. To optimize and extend the half‐life of these therapeutics, scientists have employed several strategies:

• Designing DPP‑4 resistant analogs: Many leading firms have re-engineered GLP‑1 peptides to resist rapid degradation by DPP‑4. By making key amino acid substitutions and other chemical modifications, drugs like liraglutide, dulaglutide, and semaglutide exhibit significantly prolonged half‑lives, permitting once‑weekly dosing regimens that enhance patient adherence and clinical outcomes.

• Novel formulations and drug delivery technologies: An essential focus has been on advanced drug delivery systems—such as the use of microsphere encapsulation and sustained‑release injectable devices—that ensure stable plasma concentrations over extended periods. New formulations, like those involving GLP‑1 analog–loaded poly (d,l‑lactic‑co‑glycolic acid) (PLGA) microspheres, have allowed controlled release over days or weeks. Other approaches include fusing the GLP‑1 analogs with human serum albumin or even the Fc region of monoclonal antibodies to leverage the proteins’ longer half‑life in circulation.

• Oral delivery strategies: Owing to the inconvenience of injections, companies are doubling down on research into oral formulations of GLP‑1 drugs. Efforts by Oramed Pharmaceuticals and others have focused on modifying absorption characteristics and protecting the molecule from gastrointestinal degradation. While challenging due to the molecular weight and sensitivity of peptides to digestive enzymes, these strategies are promising in terms of improving patient adherence and expanding market access.

• Combination therapies and co‑agonists: Recognizing that GLP‑1’s therapeutic spectrum can be widened, there has been substantial interest in developing combination molecules that target multiple receptors simultaneously. Unimolecular dual‑agonists and even triple‑agonists—which incorporate GLP‑1, GIP, and glucagon receptor activity—are being explored to produce synergistic effects on weight loss, glycemic control, and metabolic improvement. These novel approaches not only enhance potency but may also address varying patient needs more effectively.

Market Approaches
The market dynamics in the GLP‑1 therapeutic arena are strongly influenced by the distinct strategies that leading and emerging companies adopt:

• Patent protection and regulatory strategies: Eli Lilly and Novo Nordisk, for instance, have developed extensive intellectual property portfolios that cover both the molecules and their novel drug delivery methods. A thorough patent strategy not only protects their innovations but also establishes significant barriers for new entrants. The emphasis on regulatory exclusivities and extended patent lifetimes has been a key market approach to ensuring sustained revenue streams and maintaining their lead within the GLP‑1 market.

• Marketing and branding: Both leading companies have built powerful brands around their flagship GLP‑1 products. Ozempic, Wegovy, and Mounjaro have received widespread attention due not only to their innovative drug delivery profiles but also due to aggressive marketing strategies that emphasize the dual benefits in glycemic control and weight reduction. Such branding activities have been crucial in positioning these drugs in a rapidly growing market with significant unmet needs.

• Cost‑effective strategies and market segmentation: Emerging players are adopting market approaches that include strategic partnerships, licensing agreements, and even merger or acquisition options to gain access to advanced technologies and wider distribution channels. In doing so, they often aim to offer competitive pricing and cost‑effective solutions that can appeal to specific segments, such as patients who are unable to tolerate injectable products or those in lower- and middle‑income countries.

• Expansion of indications: Another key market strategy involves the exploration of GLP‑1’s benefits in therapeutic areas beyond diabetes and obesity. Companies are investigating the hormone’s potential for neuroprotection, treatment of cardiovascular diseases, and even applications in non‑alcoholic fatty liver disease (NAFLD). This diversified approach enables firms to tap into larger patient populations and to create differentiated products that may command premium pricing.

• Adoption of emerging technologies: The integration of advanced technologies such as physiologically based pharmacokinetic (PBPK) modeling, machine learning in drug discovery, and sophisticated biomarker-based patient selection are increasingly being used across the industry. These strategies improve the predictive efficiency of early clinical trials and reduce the overall cost of drug development by allowing fast “fail–fast” approaches. By leveraging these technologies, companies can optimize dosing regimens, reduce adverse effects, and accelerate market entry.

Market Impact and Future Outlook

Current Market Trends
The GLP‑1 class of therapeutics has already achieved blockbuster status, with studies and market forecasts predicting that annual sales will approach US$50 billion in the near term and exceed US$100 billion by 2029. The robust performance of companies’ flagship drugs such as Mounjaro, Ozempic, and Wegovy are key drivers behind these projections. These drugs, which are used both for their anti‑diabetic effects and for their weight‑loss benefits, are demonstrating a strong clinical and commercial impact.

Moreover, recent reports show that the GLP‑1 market is characterized by high demand far outpacing supply due to rapid escalation in both segment penetration and product diversification. With the consumer trend favoring minimally invasive or oral therapies and a growing emphasis on multi‑indication products (e.g., addressing both metabolic and cardiovascular parameters), the current market is poised for explosive growth. The dual focus on obesity and diabetes presents unique challenges in terms of price elasticity, reimbursement strategies, and overall health economics. Furthermore, the market strategy to maintain a duopoly in global sales—dominated by Eli Lilly and Novo Nordisk—remains a key trend, although challengers are steadily closing the gap as technologies mature and regulatory pathways become clearer.

Additionally, employers and insurers are reconsidering their benefit designs in response to the widespread use of GLP‑1 drugs. Surveys indicate that a significant proportion of employers plan to expand their coverage for these medications in 2024, a trend driven by the recognized association between improved employee health outcomes and long‑term cost savings in diabetes and obesity management. This shift in reimbursement policies is expected to further drive the adoption of GLP‑1 therapies in both clinical practice and real‑world settings.

Future Opportunities and Challenges
Looking ahead, the GLP‑1 market is likely to witness continued technological innovation and expanding clinical applications. Some of the most promising opportunities include:

• New delivery platforms: As research into oral delivery systems matures, we can expect an increasing number of oral GLP‑1 formulations. This will not only enhance patient convenience and compliance but also potentially widen the market reach to populations that are currently averse to injections.

• Expanded therapeutic indications: Beyond diabetes and obesity, GLP‑1’s beneficial effects on cardiovascular and neurodegenerative diseases suggest tremendous future potential. The expanding research into these areas, supported by promising preclinical and early clinical data, could lead to the approval of therapies targeting a broader array of conditions, thus enlarging the total addressable market.

• Combination and multi‑agonist therapies: Future drug development strategies will likely increasingly focus on combination therapies. Unimolecular dual‑ or triple‑agonists that target multiple incretin receptors (GLP-1, GIP, and even glucagon receptors) are already under clinical evaluation, which could result in enhanced metabolic outcomes and further differentiation within the market.

• Emerging small‑molecule candidates: While peptides still dominate the market, small‑molecule GLP‑1 receptor agonists are on the horizon, promising improved oral bioavailability and potentially improved cost structures. Companies like Eli Lilly, which are already leading in this area (as seen with orforglipron advancing to Phase III), and emerging biotech companies, are expected to drive further diversification in the product portfolio.

However, several challenges remain:

• Manufacturing and cost pressures: The high cost of peptide manufacturing, along with challenges in maintaining stability and bioavailability, remains a significant hurdle. Advanced delivery technologies may help ease these challenges, but they also require substantial investment in research and regulatory approval.

• Market saturation and competition: As the market expands, competition is expected to intensify not only from established giants like Eli Lilly and Novo Nordisk but also from emerging players. This competitive pressure may lead to pricing pressures and the need for continuous innovation in clinical efficacy and safety profiles.

• Regulatory and reimbursement uncertainties: The regulatory landscape for drug approvals is continually evolving. Companies must navigate complex patent portfolios, regulatory exclusivities, and variances in reimbursement policies across different regions. Future policies related to drug pricing and market exclusivity could have profound impacts on the commercial success of GLP‑1 therapies.

• Safety and tolerability issues: Although GLP‑1 receptor agonists are generally well tolerated, concerns remain regarding side effects such as gastrointestinal disturbances and, in some cases, rare but serious adverse events (e.g., pancreatitis or thyroid C‑cell tumors). Continuous post‑marketing surveillance and adaptive clinical trial designs will be necessary to address these safety concerns.

• Patient adherence and education: Changing the route of administration from injections to oral therapies is one of the primary goals of many firms. However, ensuring that patients understand and adhere to new treatment paradigms will require extensive education, support programs, and innovative monitoring tools.

Conclusion
In summary, GLP‑1 is a multifunctional hormone that has transformed the therapeutic landscape for diabetes and obesity. Its role in enhancing insulin secretion, curbing hyperglycemia, and inducing weight loss has made it a central focus in pharmaceutical research over the past several decades. The leading key players—Eli Lilly and Novo Nordisk—have successfully built robust commercial empires based on innovative formulation strategies, extensive patent portfolios, and aggressive marketing approaches that have secured them dominant positions in the GLP‑1 marketplace.

At the same time, a new generation of emerging companies, such as Terns Pharmaceuticals, Carmot Therapeutics, and Oramed Pharmaceuticals, is entering the arena with innovative strategies aimed at developing small‑molecule and oral formulations that could potentially disrupt the existing market structure. These emerging players are also benefiting from advancements in drug delivery technologies, combination therapy approaches, and personalized medicine strategies that enhance the clinical versatility of GLP‑1–based treatments.

From a drug development perspective, strategies to overcome GLP‑1’s short half‑life—ranging from molecular modifications to novel delivery systems—are central to current research and will continue to evolve. These strategies not only improve pharmacokinetics and patient adherence but also facilitate the expansion of GLP‑1 therapies to cardiovascular, neuroprotective, and metabolic indications beyond traditional diabetes and obesity. Current market trends, bolstered by strong clinical data, aggressive intellectual property management, and evolving reimbursement policies, project the GLP‑1 therapeutic class to become one of the most lucrative sectors in modern medicine, with revenues potentially exceeding US$100 billion in the coming years.

Looking forward, opportunities lie in the continued innovation of oral and small‑molecule formulations, further expansion of indications, and the incorporation of advanced technologies such as modeling and machine learning for optimizing early‑phase research. Nevertheless, challenges including manufacturing costs, intensified competition, regulatory uncertainties, and safety considerations must be carefully managed to maintain growth and market leadership.

In conclusion, the key players in the pharmaceutical industry targeting GLP‑1—predominantly Eli Lilly and Novo Nordisk—together with a growing number of emerging companies, are shaping a dynamic and rapidly evolving landscape. Their diversified strategies in terms of molecular design, delivery technology, intellectual property management, and market segmentation collectively contribute to an ecosystem poised for substantial growth. With the dual benefit of glycemic control and weight reduction, along with the potential for broader clinical applications, the GLP‑1 space is set to offer transformative benefits for patient outcomes globally, provided that the challenges are met with sustained innovation and strategic investment.