[해외, 바이오] Eli Lilly & Company: Corporate Analysis and Orforglipron Market Assessment

 

1. Executive Summary

Eli Lilly and Company (Lilly) stands as a formidable force in the global pharmaceutical industry, increasingly propelled by its highly successful incretin portfolio, notably Mounjaro® (tirzepatide) for type 2 diabetes (T2D) and Zepbound® (tirzepatide) for obesity. The company maintains a strong financial position, characterized by rapid revenue growth and significant investment in research and development (R&D). Lilly's strategic focus centers on key therapeutic areas including diabetes, obesity, oncology, immunology, and neuroscience, with a robust pipeline aimed at sustaining long-term growth.

A pivotal element of Lilly's future strategy is orforglipron, an investigational, once-daily oral glucagon-like peptide-1 (GLP-1) receptor agonist (RA). Positioned to enter the burgeoning global obesity market—forecasted to exceed $100 billion by 2030—orforglipron represents a potentially disruptive force. Its primary advantage lies in its oral administration, offering enhanced convenience over current injectable market leaders like Novo Nordisk's Wegovy® (semaglutide) and Saxenda® (liraglutide). Clinical data to date suggests orforglipron possesses efficacy competitive with injectable semaglutide, coupled with a safety profile consistent with the GLP-1 RA class.

The competitive landscape is dominated by the rivalry between Lilly and Novo Nordisk. While Novo Nordisk holds a historical lead in the GLP-1 space, Lilly's Zepbound has rapidly gained market share due to its superior efficacy. Orforglipron's anticipated launch is expected to further intensify this competition, potentially capturing share from both existing injectables and expanding the overall market by attracting patients hesitant to use injections. Successful market penetration will depend critically on final Phase 3 obesity trial (ATTAIN) results, securing regulatory approvals, implementing a competitive pricing and market access strategy, and ensuring reliable, large-scale manufacturing—an area Lilly is heavily investing in. Projections indicate continued market share gains for Lilly, potentially solidifying its leadership in the metabolic disease space. However, risks remain, including intense pipeline competition, payer pushback on pricing, regulatory hurdles, and the need for long-term safety and efficacy validation. Overall, orforglipron constitutes a major strategic opportunity for Lilly, poised to generate substantial value if successfully navigated through development and commercialization.

2. Eli Lilly and Company: Corporate Overview

2.1 Business Focus and Structure

Eli Lilly and Company operates with a singular focus on the human pharmaceutical products segment. The company's stated purpose is centered on the discovery, development, manufacturing, and marketing of medicines aimed at improving the lives of people globally. This concentrated approach allows Lilly to dedicate substantial resources and expertise towards pharmaceutical innovation, differentiating it from more diversified healthcare conglomerates. This strategic focus is fundamental to understanding its investment priorities and market approach, particularly its significant commitment to advancing treatments in high-growth therapeutic categories.  

2.2 Key Therapeutic Areas and Strategic Priorities

Lilly strategically prioritizes several core therapeutic areas poised for significant growth and addressing unmet medical needs: Diabetes, Obesity, Oncology, Immunology, and Neuroscience. The company's R&D and business development activities reflect this focus, actively seeking external collaborations and technologies to bolster its internal pipeline. Areas of particular interest include novel mechanisms within the obesity space, such as GLP-1/incretin add-on therapies (both oral and injectable), approaches targeting body composition (lean mass preservation), energy expenditure modulation, and mitochondrial health. Furthermore, Lilly is investing in advanced platforms like genetic medicines, oligonucleotide therapeutics, AI/ML applications in drug discovery, and novel drug delivery systems, including those targeting the blood-brain barrier.  

This strategic alignment, particularly the heavy emphasis on metabolic diseases (diabetes and obesity) and oncology, positions Lilly to capitalize on major market trends and demographic shifts. The deep exploration of diverse mechanisms within obesity signals a long-term commitment extending beyond its current successful incretin therapies, aiming for next-generation solutions. The concentration on overlapping fields like diabetes and obesity enables significant operational synergies. R&D insights, manufacturing processes (especially for complex biologics like incretins), and specialized commercial infrastructure can be leveraged across multiple high-value products within this cardiometabolic cluster. This focused synergy can accelerate development timelines and enhance market penetration efficiency compared to companies managing more disparate portfolios.  

2.3 Key Product Portfolio Performance

Lilly's revenue stream is increasingly powered by its newer pharmaceutical assets. Key products driving growth include Mounjaro® (tirzepatide for T2D), Zepbound® (tirzepatide for obesity), Verzenio® (abemaciclib for oncology), Jardiance® (empagliflozin for diabetes, partnered with Boehringer Ingelheim), and Taltz® (ixekizumab for immunology). Mounjaro and Zepbound, sharing the dual GIP/GLP-1 RA tirzepatide, have become central pillars of Lilly's recent commercial success, demonstrating rapid uptake.  

Conversely, Trulicity® (dulaglutide), another GLP-1 RA for T2D, experienced a slight revenue decline in 2023 (4% globally) despite strong underlying demand, primarily due to lower realized prices and ongoing supply constraints which are expected to persist. This highlights the competitive pressures within the GLP-1 market and potential cannibalization effects from the company's own newer, more potent agents like Mounjaro.  

The oncology portfolio, led by the strong performance of Verzenio® (56% global revenue growth in 2023), and the immunology portfolio, anchored by Taltz®, also contribute significantly to growth. Legacy products, such as the insulin Humalog®, face considerable pricing pressure, leading to revenue declines (19% globally in 2023). Older oncology drugs like Alimta® have seen sharp revenue drops due to generic competition. The portfolio's evolution underscores Lilly's successful transition towards innovative, high-growth medicines, particularly within the metabolic and oncology domains. However, the pronounced success and substantial revenue contribution from the tirzepatide franchise (Mounjaro/Zepbound) also signifies an increasing reliance on this single molecule and the broader incretin class. This reliance makes pipeline diversification and the development of next-generation therapies, such as orforglipron, strategically imperative to mitigate potential future risks associated with this concentration.  

2.4 Financial Health and Recent Performance (2023/Q4 2024)

Eli Lilly demonstrated robust financial performance in recent periods, largely fueled by its incretin franchise. Full-year 2023 revenue climbed 20% to $34.12 billion, driven by increased volume for key products like Mounjaro, Verzenio, and Jardiance, alongside higher realized prices in some areas and strategic divestitures (olanzapine portfolio, Baqsimi rights). U.S. revenue grew 20%, while revenue outside the U.S. increased 19%. Mounjaro alone generated $5.16 billion globally in 2023, a dramatic increase from $482.5 million in 2022.  

This strong top-line momentum continued into the fourth quarter of 2024, with revenue surging 45% year-over-year to $13.53 billion. This growth was overwhelmingly driven by volume increases for Mounjaro (Q4 sales: $3.53 billion) and Zepbound (Q4 sales: $1.91 billion). Notably, Lilly's non-incretin product portfolio also exhibited healthy growth, increasing 20% in Q4 2024 compared to the prior year, indicating strength beyond the metabolic blockbusters.  

Despite the strong revenue growth, reported net income and earnings per share (EPS) decreased by 16% in 2023 ($5.24 billion net income, $5.80 diluted EPS) compared to 2022. This was primarily attributed to significantly higher acquired in-process research and development (IPR&D) charges and increased investments in R&D and marketing, selling, and administrative (MS&A) expenses. However, profitability showed strong recovery in Q4 2024, with reported net income doubling to $4.41 billion (non-GAAP net income up 114% to $4.81 billion). Lilly maintains a substantial commitment to innovation, with R&D expenditures reaching nearly $11.0 billion in 2024, representing 24.4% of sales.  

Looking ahead, Lilly provided strong 2025 revenue guidance of $58.0 billion to $61.0 billion, representing approximately 32% growth at the midpoint compared to expected 2024 revenue. This guidance underscores the company's confidence in the continued ramp-up of Mounjaro and Zepbound, alongside contributions from its diversified portfolio and pipeline advancements. It is worth noting, however, that expected Q4 2024 revenue came in slightly below prior guidance, attributed to slower-than-anticipated acceleration in the U.S. incretin market growth for the quarter and lower year-end channel inventory. While Lilly expressed confidence in supply availability during Q4 , this slight miss warrants monitoring of market dynamics and inventory levels.  

2.5 Strategic Position and Outlook

Eli Lilly is firmly positioned as a leading global pharmaceutical innovator, particularly dominant in the rapidly expanding metabolic disease market. Its strategic outlook is heavily influenced by the continued success of its incretin franchise and the progression of its robust late-stage pipeline, which includes numerous new molecular entities and indication expansions across its core therapeutic areas.  

Recognizing the unprecedented demand for its incretin therapies (Mounjaro/Zepbound) and learning from competitor challenges, Lilly has made manufacturing capacity a central strategic priority. The company has committed over $23 billion since 2020 to expand its manufacturing footprint in the U.S. and Europe. This aggressive investment aims to mitigate supply constraints and ensure product availability, positioning reliable supply as a potential competitive advantage. Lilly anticipates producing at least 60% more saleable doses of incretins in the first half of 2025 compared to the first half of 2024, with new facilities like the Concord plant expected to come online during 2025.  

Furthermore, Lilly is adapting its commercial strategy by exploring direct-to-consumer (DTC) channels through its LillyDirect platform. This initiative, which includes self-pay options for medications like Zepbound , suggests a move to capture more value, enhance patient access (particularly for those facing insurance barriers), and potentially build direct relationships with consumers in the lucrative self-pay market segment. This approach, coupled with massive manufacturing scale-up and continued R&D investment, solidifies Lilly's strategy to challenge Novo Nordisk's historical dominance and lead the next wave of innovation in metabolic and other key therapeutic areas.  

3. The Emerging Oral Obesity Market and Orforglipron

3.1 Global Obesity Epidemic: Market Size and Growth Projections

The global prevalence of obesity has reached epidemic proportions, creating a significant public health crisis and a vast potential market for effective treatments. According to the World Health Organization (WHO), in 2022, more than one billion people worldwide were living with obesity, comprising approximately 890 million adults and 160 million children and adolescents aged 5-19. This represents a dramatic increase since 1990, with adult obesity prevalence more than doubling and adolescent obesity quadrupling during that period. Furthermore, 43% of the global adult population (2.5 billion people) were classified as overweight in 2022. In the United States, the situation is particularly acute, with CDC data indicating an adult obesity rate of 41.9% in 2022, and all states reporting rates above 25%.  

Obesity is a major risk factor for numerous noncommunicable diseases (NCDs), including cardiovascular diseases, type 2 diabetes, certain cancers, and musculoskeletal disorders, contributing to an estimated 5 million deaths from NCDs in 2019. Beyond the health impact, the economic burden is substantial, with global costs associated with overweight and obesity projected to reach $3 trillion annually by 2030 and potentially exceeding $18 trillion by 2060 if current trends continue.  

This immense and growing patient population, coupled with the increased recognition of obesity as a serious chronic disease requiring medical intervention, has fueled forecasts of explosive growth for the anti-obesity medication (AOM) market. Having registered approximately $6 billion in sales in 2023 , the market is projected to expand dramatically. Morgan Stanley Research significantly revised its forecast upwards, now anticipating the global obesity drug market to reach $105 billion by 2030, with potential upside to $144 billion, a substantial increase from its earlier $77 billion estimate. Other analysts offer similarly bullish projections, with Goldman Sachs predicting up to $130 billion by 2030 , and GlobalData forecasting the GLP-1RA market alone (which dominates obesity treatment) could hit $125 billion by 2033. The anticipated compound annual growth rate (CAGR) for the anti-obesity drug market is estimated at a robust 21.1% through 2035. This rapid market expansion reflects the paradigm shift driven by the arrival of highly effective incretin-based therapies, transforming obesity treatment from a niche area to a potential mass market and justifying the significant investments being made by pharmaceutical leaders.  

3.2 Orforglipron: Profile of an Oral GLP-1 Receptor Agonist

Amidst the rapidly expanding obesity market, Eli Lilly is advancing orforglipron, an investigational therapy poised to offer a distinct profile compared to current market leaders.

3.2.1 Mechanism of Action and Differentiation

Orforglipron (LY-3502970) is classified as an oral, nonpeptide, small molecule glucagon-like peptide-1 (GLP-1) receptor agonist. Its mechanism involves binding to and activating the GLP-1 receptor, primarily located on pancreatic beta cells but also present in the brain, gut, and other tissues. This activation mimics the effects of the endogenous incretin hormone GLP-1, leading to several physiological responses relevant to both diabetes and obesity management: glucose-dependent stimulation of insulin secretion, suppression of glucagon release, delayed gastric emptying, and promotion of satiety signals in the brain, which reduces appetite and food intake.  

The key differentiating factor for orforglipron lies in its oral administration and small molecule structure. Unlike the peptide-based structures of injectable GLP-1 RAs like semaglutide (Wegovy/Ozempic) and liraglutide (Saxenda/Victoza), orforglipron's small molecule nature is designed to allow for effective absorption through the gastrointestinal tract after oral ingestion. This eliminates the need for subcutaneous injections, a significant convenience factor and potential barrier to uptake for some patients. Additionally, being a nonpeptide small molecule may offer advantages in terms of manufacturing complexity and cost compared to large peptide molecules, potentially supporting more scalable production. Orforglipron is also designed to resist degradation by the DPP-4 enzyme, which rapidly breaks down native GLP-1, contributing to its sustained action. Pharmacologically, preclinical studies suggest orforglipron exhibits biased agonism, preferentially activating the cAMP signaling pathway over β-arrestin recruitment, a profile hypothesized to potentially reduce receptor desensitization, though the clinical significance of this bias remains unproven.  

3.2.2 Clinical Efficacy and Safety Profile (Phase 2 & Phase 3 ACHIEVE-1)

Clinical trial data available to date indicate that orforglipron demonstrates significant efficacy in both weight reduction and glycemic control.

• Phase 2 Obesity Trial (NEJM): This study enrolled adults with obesity or overweight with comorbidities but without diabetes. Results showed dose-dependent weight loss. At the 36-week mark, the mean percentage change in body weight from baseline ranged from -9.4% to -14.7% across the orforglipron dose groups (12mg, 24mg, 36mg, 45mg), compared to -2.3% in the placebo group. A substantial proportion of participants achieved clinically significant weight loss: 46% to 75% of those on orforglipron lost at least 10% of their baseline body weight by week 36, versus only 9% of those on placebo. The trial also reported improvements in various prespecified weight-related and cardiometabolic measures.  

• Phase 2 Type 2 Diabetes Trial (Lancet): In adults with T2D, orforglipron demonstrated potent glycemic control and weight loss effects. At 26 weeks, it achieved mean reductions in HbA1c of up to 2.1% (from a baseline of 8.1%), compared to -0.43% for placebo and -1.10% for the active comparator dulaglutide (an injectable GLP-1 RA). Concurrently, orforglipron led to mean body weight reductions of up to 10.1 kg (22.3 lbs), significantly greater than the -2.2 kg loss with placebo and -3.9 kg loss with dulaglutide.  

• Phase 3 ACHIEVE-1 Trial (Type 2 Diabetes): The first Phase 3 readout, ACHIEVE-1, evaluated orforglipron as monotherapy in adults with T2D inadequately controlled with diet and exercise. The trial successfully met its primary endpoint at 40 weeks, demonstrating superior HbA1c reduction compared to placebo. Mean A1C decreased by 1.3% to 1.6% across the orforglipron doses (3mg, 12mg, 36mg) from a baseline of 8.0%, versus a 0.1% reduction with placebo. A key secondary endpoint showed that over 65% of participants taking the highest dose (36mg) achieved an A1C level of ≤6.5%, below the ADA threshold for diabetes diagnosis. Significant weight loss was also observed as a key secondary outcome, with participants on the 36mg dose losing an average of 7.3 kg (16.0 lbs), representing 7.9% of their baseline weight (90.2 kg). Importantly, the weight loss trajectory had not plateaued by the 40-week time point, suggesting potential for further reduction with longer treatment duration.  

• Safety and Tolerability: Across trials, the safety profile of orforglipron has been reported as consistent with the established GLP-1 receptor agonist class. The most frequently reported adverse events (AEs) are gastrointestinal (GI) in nature, including nausea, diarrhea, vomiting, and constipation. These events are typically mild to moderate in severity and tend to occur most often during the initial dose-escalation period. Discontinuation rates due to AEs varied: in the Phase 2 obesity trial, 10% to 17% of participants across dose cohorts stopped treatment due to AEs , while in the Phase 3 ACHIEVE-1 T2D trial, discontinuation rates were lower, ranging from 4% to 8% across the active doses. No concerning liver safety signals were identified in the ACHIEVE-1 trial.  

These results suggest orforglipron possesses clinically meaningful efficacy, approaching the weight loss seen with injectable semaglutide (~15%) and demonstrating robust glycemic control comparable to established injectable GLP-1s. While GI side effects are common and lead to some discontinuations, the overall safety profile appears manageable and predictable for the drug class. The pending results from the Phase 3 ATTAIN program, specifically evaluating orforglipron for chronic weight management in individuals without diabetes, will be crucial for confirming its efficacy and safety in the primary target obesity population.  

3.2.3 Potential Advantages

The primary potential advantage of orforglipron lies in its oral, once-daily administration, which can be taken without restrictions related to food or water intake. This offers a significant improvement in convenience compared to the currently dominant injectable GLP-1 RAs (Wegovy requires weekly injection, Saxenda daily). This ease of use could overcome patient aversion to needles, simplify treatment regimens, and potentially enhance long-term adherence, a critical factor in managing chronic conditions like obesity.  

Furthermore, as a small molecule, orforglipron may possess inherent advantages in manufacturing scale-up and potentially lower production costs compared to complex peptide-based biologics. This underpins Lilly's stated confidence in its ability to launch orforglipron globally without the supply constraints that have plagued the incretin market previously. If these manufacturing efficiencies translate into competitive pricing and, crucially, reliable supply, orforglipron could rapidly capture significant market share.  

Finally, its demonstrated efficacy appears competitive with high-efficacy injectable GLP-1s like semaglutide , offering a compelling combination of effectiveness and convenience. Its long pharmacokinetic half-life (reported as 29 to 49 hours) supports the feasibility and effectiveness of once-daily dosing. The immense size of the obesity market, combined with known patient barriers to injectable therapies, suggests a substantial unmet need for an effective and convenient oral option. Orforglipron, with its promising clinical profile and user-friendly administration, appears well-timed to potentially unlock a large segment of this market currently underserved or hesitant to initiate injectable treatment.  

3.2.4 Development Status and Timeline

Orforglipron, originally discovered by Chugai Pharmaceutical Co., Ltd. and licensed to Eli Lilly in 2018 , is currently undergoing extensive Phase 3 clinical development. The program encompasses two main suites of trials: ACHIEVE for type 2 diabetes and ATTAIN for chronic weight management.  

The ACHIEVE program has enrolled over 6,000 participants across five global registrational trials. The first positive topline results, from ACHIEVE-1 (evaluating orforglipron monotherapy vs. placebo in T2D), were announced in April 2025. Further results from the ACHIEVE program are anticipated later in 2025 and extending into 2026.  

The ATTAIN program focuses on orforglipron for obesity and overweight individuals, including studies in adolescents and for weight maintenance. Key results from the ATTAIN trials evaluating orforglipron for weight management are expected later in 2025.  

Based on this timeline, Eli Lilly plans to submit orforglipron to global regulatory agencies for the weight management indication by the end of 2025. Submission for the type 2 diabetes indication is anticipated in 2026. This staggered approach suggests Lilly views obesity as the primary initial commercial opportunity, likely driven by the larger potential patient population and the timing of the ATTAIN data readouts. A potential market launch could occur as early as 2026, setting the stage for near-term competition with established injectable therapies.  

3.3 Estimated Pricing Strategy and Market Access Considerations

While definitive pricing for orforglipron has not been announced, the existing market provides crucial context for Lilly's potential strategy. Current list prices for the leading injectable obesity medications, Wegovy and Saxenda, are substantial, hovering around $1,350 per month in the U.S.. However, the competitive landscape has driven aggressive discounting in the cash-pay market segment. Novo Nordisk recently established a significant benchmark by offering Wegovy at a cash price of $499 per month through its NovoCare Pharmacy program and now extended to retail pharmacies for eligible patients (uninsured or those whose commercial insurance doesn't cover obesity meds). Similarly, Lilly offers vial presentations of its highly effective injectable Zepbound through its LillyDirect Self Pay platform at prices starting at $249 or $499 per month, depending on the dose.  

Orforglipron's pricing will be a critical determinant of its market uptake. As an oral small molecule, it might benefit from lower manufacturing costs compared to complex peptide injectables , potentially allowing for more competitive pricing. However, the significant R&D investment and the high demand anticipated for an effective oral option could also support premium pricing relative to older generics or less effective treatments. Lilly's emphasis on its ability to manufacture orforglipron "at scale" without supply constraints might also enable a strategy focused on volume, potentially supported by competitive pricing.  

The $499 per month cash price point established by Novo Nordisk for Wegovy likely sets a competitive expectation for the self-pay market that Lilly will need to consider for orforglipron, leveraging its existing LillyDirect infrastructure. Beyond the cash-pay segment, securing broad payer coverage will be paramount for achieving mass-market adoption. Currently, insurance coverage for AOMs remains inconsistent, with many plans imposing significant restrictions (e.g., prior authorizations, step edits) or excluding coverage altogether, despite growing recognition of obesity as a chronic disease. Lilly will need to demonstrate strong clinical value, including the cardiometabolic improvements observed in trials , to convince payers of orforglipron's cost-effectiveness and secure favorable formulary placement, potentially including efforts to gain Medicare coverage. The ultimate success of orforglipron will depend heavily on achieving a balance between price, perceived value (efficacy and convenience), and broad market access.  

4. Competitive Landscape: Novo Nordisk's Incumbents

The primary competitor for Eli Lilly in the incretin-based obesity treatment market is Novo Nordisk, which pioneered the GLP-1 RA class for this indication.

4.1 Wegovy (Semaglutide): Profile and Market Performance

Wegovy is an injectable, peptide-based GLP-1 receptor agonist administered once weekly via subcutaneous injection. It received FDA approval for chronic weight management in adults with obesity or overweight with at least one weight-related comorbidity in June 2021. Significantly, in March 2024, its label was expanded to include the reduction of risk of major adverse cardiovascular events (MACE) in adults with established cardiovascular disease and either obesity or overweight.  

• Efficacy: Wegovy set a high benchmark for weight loss efficacy among early GLP-1 RAs. Clinical trials within the STEP program demonstrated average weight loss ranging from approximately 15% to 17% over 68 weeks, depending on the study population and design. The pivotal STEP 1 trial showed a mean weight loss of 14.9%.  
• Safety: Its safety profile is characteristic of the GLP-1 RA class. The most common side effects are gastrointestinal, including nausea, diarrhea, vomiting, and constipation, particularly during the initial titration phase. The prescribing information includes a boxed warning regarding the potential risk of thyroid C-cell tumors, based on findings in rodents. Other warnings include risks of pancreatitis, gallbladder problems (including gallstones), acute kidney injury, potential worsening of diabetic retinopathy in T2D patients, increased heart rate, and rare reports of suicidal behavior or thinking.  
• Pricing and Access: Wegovy carries a high list price, approximately $1,349 per month in the U.S.. However, Novo Nordisk employs aggressive access strategies. For patients with commercial insurance coverage, copay assistance programs mean that a reported 90% pay between $0 and $25 per month. For the significant cash-paying segment (uninsured or not covered for AOMs), the NovoCare Pharmacy program offers all doses at $499 per month, available via direct home delivery and now also through traditional retail pharmacies.  
• Market Performance: Wegovy rapidly achieved blockbuster status following its launch, driving substantial revenue growth for Novo Nordisk despite initial significant manufacturing supply constraints. U.S. sales reached $6.4 billion in 2024, with global sales hitting $9.4 billion. While supply issues have largely been resolved , Wegovy now faces intense competition from Lilly's Zepbound, which demonstrates superior weight loss efficacy. Wegovy's established market presence, brand recognition, and crucial cardiovascular risk reduction indication remain key strengths, bolstered by the aggressive $499 cash price point designed to defend its market share.  

4.2 Saxenda (Liraglutide): Profile and Market Performance

Saxenda is also an injectable, peptide-based GLP-1 receptor agonist, but it requires once-daily subcutaneous administration. It was the first GLP-1 RA to gain FDA approval specifically for chronic weight management back in 2014.  

• Efficacy: Clinical trials (SCALE program) showed more modest weight loss compared to newer agents. The SCALE Obesity and Prediabetes trial reported an average weight loss of approximately 8.4% over 56 weeks. Other analyses suggest an average weight loss of 5-6 kg (11-13 lbs) greater than placebo over one year. While clinically significant (typically defined as ≥5% loss), this efficacy is considerably lower than that achieved with Wegovy or Zepbound. Studies showed that about 62% of patients lost ≥5% and 34% lost ≥10% of their baseline weight in the main trial. Weight loss can be sustained over longer periods (up to 3 years) in patients who respond well initially.  
• Safety: Saxenda shares the common GLP-1 RA class side effect profile, dominated by GI issues like nausea (39% incidence reported in one source), vomiting (16%), diarrhea (21%), and constipation (19%). It may have a higher frequency of injection site reactions compared to Wegovy. Similar warnings regarding thyroid C-cell tumors, pancreatitis, and gallbladder issues apply. Approximately 10% of patients discontinue treatment due to adverse effects.  
• Pricing and Access: Saxenda's list price is similar to Wegovy's, around $1,350 per month , although some sources report average retail prices closer to $1,802. Discount programs like SingleCare may reduce the cost to around $1,189. Unlike Wegovy, Saxenda does not currently benefit from a widely publicized $499 cash-pay program, potentially making it less accessible for self-paying patients. Insurance coverage can vary and may be less favorable than for newer agents.  
• Market Performance: As the first entrant, Saxenda established the GLP-1 RA category for obesity. However, its lower efficacy and less convenient daily dosing schedule have led to it being largely superseded by weekly injectables like Wegovy and Zepbound. Its market share is diminishing, with U.S. sales reported at $345 million in 2024. It likely retains a niche role for specific patient populations or based on formulary access.  

4.3 Novo Nordisk's Market Position and Strategy

Novo Nordisk holds a legacy of leadership in diabetes care and pioneered the use of GLP-1 therapies, leveraging this expertise to enter the obesity market. The company maintains a dominant global volume market share in the overall GLP-1 market (including diabetes indications like Ozempic and Rybelsus), reported at 63% as of November 2024. This reflects a massive patient reach, nearly tripling from approximately 4 million to 12 million patients globally between November 2021 and November 2024.  

However, in the specific, high-growth obesity segment, Novo Nordisk is facing an unprecedented challenge from Eli Lilly's Zepbound. While Wegovy remains a multi-billion dollar product, its market share is under pressure due to Zepbound's superior efficacy profile.  

Novo Nordisk's strategy appears multi-faceted:

1. Maximize Existing Assets: Expanding Wegovy's label to include cardiovascular risk reduction adds significant clinical value and differentiation. Aggressive pricing strategies, exemplified by the $499 NovoCare cash price for Wegovy, aim to defend market share, particularly in the self-pay segment, and maintain volume.  
2. Scale Manufacturing: Like Lilly, Novo Nordisk is investing heavily in expanding its manufacturing capacity to meet the enormous demand for GLP-1 therapies and avoid past supply bottlenecks.  
3. Pipeline Advancement: Novo Nordisk is developing next-generation obesity treatments to compete more effectively on efficacy and potentially modality. Key pipeline assets include CagriSema, a combination of semaglutide and cagrilintide (an amylin analogue), and oral amycretin, another dual-agonist candidate aiming to provide high efficacy in a convenient pill form.  

Novo Nordisk is leveraging its established infrastructure, brand recognition, and large patient base, but is clearly in a defensive posture in the obesity market against Lilly's current momentum. The success of its pipeline candidates will be critical for its long-term competitive position. The company's willingness to significantly cut the cash price of Wegovy signals a strategic prioritization of volume and market presence over maximizing list price realization in certain segments, likely anticipating further pressure from Lilly's portfolio, including the impending arrival of orforglipron.

5. Comparative Analysis: Orforglipron vs. Wegovy vs. Saxenda

A direct comparison highlights the distinct profiles and potential positioning of Eli Lilly's orforglipron against Novo Nordisk's established injectable therapies, Wegovy and Saxenda.

5.1 Efficacy Comparison (Weight Loss %)

A clear hierarchy in weight loss efficacy has emerged among these agents, based on clinical trial data:

• Wegovy (Semaglutide): Demonstrates high efficacy, with average weight loss typically reported in the range of ~15% to 17% over 68 weeks in major clinical trials. This level of weight loss set the benchmark for the current generation of highly effective obesity medications.  
• Orforglipron: Phase 2 results showed promising efficacy, with mean weight loss up to 14.7% at 36 weeks. Phase 3 data in T2D also showed significant weight loss (7.9% at 40 weeks, not plateaued). While final Phase 3 obesity data (ATTAIN) is pending, expectations are that orforglipron will achieve weight loss competitive with Wegovy (~15%), potentially offering similar efficacy in an oral formulation.  
• Saxenda (Liraglutide): Shows more modest efficacy compared to the newer agents, with average weight loss around ~6% to 8% over 56 weeks in its pivotal trials.  

While Lilly's other obesity drug, Zepbound (tirzepatide), offers even higher efficacy (~20-22%) , orforglipron's target appears to be matching Wegovy's efficacy level. Achieving this ~15% threshold is likely crucial for market acceptance, as Saxenda's experience suggests the market strongly favors higher weight loss outcomes. If orforglipron meets this benchmark, its oral convenience could make it a highly attractive alternative to injectable Wegovy.  

5.2 Safety and Tolerability Profiles

All three medications belong to the GLP-1 receptor agonist class and share a generally similar safety and tolerability profile, primarily characterized by gastrointestinal (GI) side effects.

• Common Side Effects: Nausea, vomiting, diarrhea, and constipation are the most frequently reported adverse events for orforglipron, Wegovy, and Saxenda, particularly during the initial dose titration period as the body adapts to the medication. These are typically mild to moderate in severity.  
• Discontinuation Rates: Discontinuation due to adverse events occurs in a subset of patients. Reported rates vary by trial, dose, and patient population, but generally fall in the range of roughly 5% to 17% across the drugs (Orforglipron Phase 2 obesity: 10-17% ; Orforglipron Phase 3 T2D: 4-8% ; Saxenda: ~10% ). Final Phase 3 data for orforglipron in obesity will provide a clearer comparison.  
• Serious Warnings: All three drugs carry warnings related to potential serious risks associated with the GLP-1 class, including pancreatitis, gallbladder disease (gallstones), potential kidney injury (often linked to dehydration from GI side effects), increased heart rate, and the boxed warning regarding thyroid C-cell tumors observed in rodent studies (though the relevance to humans is uncertain). Rare instances of suicidal ideation have also been reported.  

Orforglipron's safety profile observed in Phase 2 and the initial Phase 3 T2D trial appears consistent and predictable based on extensive experience with the GLP-1 RA class. While the overall safety profiles converge, subtle differences in the relative frequency or patient experience of specific GI effects (e.g., whether nausea or diarrhea is more prominent ) could emerge with wider use and potentially influence individual patient or physician preference.  

5.3 Dosing, Administration, and Convenience

This is the area where orforglipron offers the most significant potential differentiation:

• Orforglipron: Designed as a once-daily oral pill that can be taken without restrictions on food or water intake.  
• Wegovy: Requires a once-weekly subcutaneous injection.  
• Saxenda: Requires a once-daily subcutaneous injection.  

Orforglipron clearly provides the highest level of administration convenience. Eliminating injections altogether addresses a major barrier for needle-averse patients and simplifies the treatment routine considerably compared to both weekly and especially daily injections. This convenience factor is expected to be a primary driver of its appeal in the market.

5.4 Pricing and Cost-Effectiveness Analysis

Pricing remains a critical variable, with orforglipron's specific strategy yet to be revealed.

• List Prices: Wegovy and Saxenda share similar high list prices around $1,350 per month in the U.S.. Orforglipron's list price is TBD.  
• Discounted/Cash Prices: The competitive dynamics have led to significant discounting for cash-paying patients through specific programs. Wegovy is available for $499/month via NovoCare and retail partnerships. Lilly offers Zepbound vials starting at $249 or $499/month via LillyDirect Self Pay. Saxenda currently lacks a comparable widely available low cash price program.  
• Access: Insurance coverage remains a major hurdle for many patients seeking AOMs, with variable coverage and frequent requirements for prior authorization or step therapy.  

Orforglipron's pricing strategy will be pivotal. A lower list price compared to injectables, potentially enabled by lower manufacturing costs for a small molecule , could be highly disruptive. Alternatively, Lilly might price it similarly to injectables on a list basis but compete aggressively in the cash-pay market via LillyDirect, leveraging the $499/month benchmark set by Wegovy. Cost-effectiveness analyses, crucial for securing favorable payer coverage, will need to weigh orforglipron's efficacy (including cardiometabolic benefits ) against its net cost and the potential long-term savings from reduced obesity-related comorbidities.  

5.5 Comparative Summary Table

The key differences and similarities are summarized below:

Feature	Orforglipron (Lilly)	Wegovy (Novo Nordisk)	Saxenda (Novo Nordisk)
Mechanism	Oral, nonpeptide GLP-1 RA (Small Molecule)	Injectable GLP-1 RA (Peptide)	Injectable GLP-1 RA (Peptide)
Administration	Once-daily pill (no restrictions)	Once-weekly injection	Once-daily injection
Avg. Weight Loss (%)	~14.7% (Ph 2, 36wks); Ph 3 pending (~15% est.)	~15-17% (STEP trials, 68wks)	~6-8% (SCALE trials, 56wks)
Key Side Effects	GI (Nausea, Diarrhea, Vomiting)	GI (Nausea, Diarrhea, Vomiting)	GI (Nausea, Vomiting, Diarrhea)
List Price (US, ~)	TBD	$1,350 / month	$1,350 / month
Discounted Cash Price (US, ~)	TBD (via LillyDirect?)	$499 / month (via NovoCare/Retail)	No ~$500 program; ~$1,189 (SingleCare)
CV Benefit Label	No	Yes (Approved for CV risk reduction in CVD pts)	No

Sources:  

This comparison underscores the potential market segmentation. Patients prioritizing maximal efficacy might still opt for the injectable Zepbound. However, orforglipron targets the large segment seeking high efficacy (~15%) combined with the unparalleled convenience of an oral pill. Wegovy remains a strong competitor with proven efficacy and a CV label advantage, but faces pressure from Zepbound on efficacy and orforglipron on convenience. Saxenda is relegated to a lower tier due to lower efficacy and daily injections. As multiple drugs demonstrate high efficacy and broadly similar safety profiles, differentiating factors like administration modality, specific side effect nuances, price/access, and additional labeled benefits (like Wegovy's CV indication) will likely become increasingly important drivers of treatment choice.

6. Market Share Dynamics and Profitability Assessment

6.1 Projected Market Penetration for Orforglipron

The potential market for effective obesity treatments like orforglipron is immense, driven by the global scale of the obesity epidemic. Despite the availability of highly effective injectable GLP-1 RAs, current market penetration remains relatively low compared to the eligible patient population. Estimates suggest that even by 2035, only around 7% to 9% of the U.S. population might be using these drugs.  

Orforglipron's key differentiator—oral administration without dosing restrictions—has the potential to significantly broaden the appeal of GLP-1 therapy and accelerate market penetration. By removing the barrier of injections, it could attract a substantial number of patients who are currently untreated or hesitant to start injectable therapy. This suggests orforglipron may not only capture share from existing treatments but also contribute significantly to expanding the overall size of the treated market.  

Combined with Lilly's stated confidence in its ability to manufacture and supply orforglipron at scale without constraints , and assuming positive Phase 3 ATTAIN results confirming Wegovy-like efficacy, orforglipron is positioned for potentially rapid and substantial market uptake upon launch. Projections, such as GlobalData's forecast of $11.8 billion in sales for orforglipron by 2030 , indicate expectations for multi-billion dollar peak sales, reflecting its potential to become a cornerstone therapy in obesity management.  

6.2 Estimated Profit and Loss Analysis for Orforglipron

A precise quantitative profit and loss (P&L) forecast for orforglipron requires specific data on net pricing, manufacturing costs (Cost of Goods Sold - COGS), R&D cost allocation, and launch-related Selling, General & Administrative (SG&A) expenses, which are not yet fully available. However, a qualitative assessment based on market context suggests significant profit potential.

• Revenue: Given the projected market size exceeding $100 billion by 2030 , achieving even a moderate market share (e.g., 10-15%) could translate into annual revenues well over $10 billion for orforglipron at peak.  
• Gross Margin: The pharmaceutical industry, and Lilly specifically, typically enjoys high gross margins. Lilly's overall gross margin was reported around 82-83% in Q4 2024. While specific margins for orforglipron are unknown, small molecule drugs can sometimes have lower COGS compared to complex biologics , potentially supporting strong gross profitability.  
• Operating Expenses: Launching a major drug like orforglipron will require substantial investment in marketing and sales (SG&A). R&D costs associated with its extensive Phase 3 program also need to be recouped.  
• Net Profitability: The ultimate profitability will heavily depend on the net price realized after accounting for rebates to payers, channel discounts (including potential aggressive pricing via LillyDirect similar to the $499 benchmark for Wegovy ), and patient assistance programs. Intense competition could pressure net pricing, potentially compressing net margins even if list prices remain high and gross margins are strong.  

Despite these variables, the sheer scale of the revenue opportunity suggests that if orforglipron achieves its target profile (Wegovy-like efficacy, oral convenience, reliable supply) and secures reasonable market access, it is highly likely to become a major profit contributor for Eli Lilly. The key factor determining the magnitude of this contribution will be the achievable net price in a competitive and cost-conscious environment.

6.3 Anticipated Shifts in Market Share (Eli Lilly vs. Novo Nordisk)

The competitive dynamic between Eli Lilly and Novo Nordisk in the GLP-1 market, particularly for obesity, is rapidly evolving, with Lilly making significant inroads into Novo Nordisk's historical dominance. While Novo Nordisk still holds the largest overall GLP-1 volume share globally (63% in Nov 2024, including diabetes drugs like Ozempic/Rybelsus) , the obesity-specific market tells a different story.  

Lilly's Zepbound, leveraging the superior weight loss efficacy of tirzepatide, has experienced remarkable uptake since its launch. By the end of Q4 2024, Zepbound had already captured over 48% of total prescriptions (TRx) and nearly 56% of new prescriptions (NBRx) in the U.S. branded anti-obesity market, rapidly eroding Wegovy's lead. Projections suggest Zepbound could capture around 35% of the overall obesity market by 2032.  

The introduction of orforglipron is expected to further accelerate Lilly's market share gains. Orforglipron's unique profile—offering high efficacy combined with oral convenience—positions it to compete effectively against both Wegovy (by offering similar efficacy with better convenience) and potentially even Zepbound (for patients prioritizing convenience over maximizing efficacy above the ~15% threshold). It is also likely to expand the market by attracting new patients.

This creates a powerful two-pronged strategy for Lilly: Zepbound targeting patients seeking the absolute highest level of weight loss, and orforglipron appealing to those prioritizing convenience while still achieving substantial results. This dual offering, catering to the two major patient preference segments, could allow Lilly to capture a larger combined share of the obesity market than Novo Nordisk, whose current portfolio relies heavily on semaglutide (Wegovy/Ozempic/Rybelsus) and liraglutide (Saxenda). While Novo Nordisk has promising pipeline assets like CagriSema and oral amycretin , Lilly is likely to have both Zepbound and orforglipron established in the market first. Morgan Stanley forecasts that Lilly and Novo Nordisk will collectively dominate the obesity pharmaceutical market, holding a combined 84% share in 2035 , but the balance of power within that duopoly appears to be shifting significantly towards Lilly.  

6.4 Factors Influencing Future Market Dynamics

The future trajectory of the obesity drug market and the relative positions of Eli Lilly and Novo Nordisk will be shaped by several critical factors:

• Clinical Trial Outcomes: Final Phase 3 results for orforglipron's ATTAIN program are paramount. Similarly, data readouts for competitor pipeline drugs, such as Novo Nordisk's CagriSema and oral amycretin , and candidates from other players like Amgen, Pfizer, Roche, and Viking Therapeutics , will be crucial.  
• Pricing and Market Access: Aggressive pricing strategies (like the $499 cash price point) and evolving payer coverage policies (including potential Medicare coverage) will significantly impact uptake and affordability. Demonstrating value beyond weight loss (e.g., cardiovascular or renal benefits) will be key for securing favorable formulary access.  
• Manufacturing and Supply: Ensuring reliable, large-scale manufacturing capacity to meet enormous demand remains a critical differentiator. Companies that can avoid supply disruptions will have a significant advantage.  
• Regulatory Decisions and Label Expansions: Global regulatory approvals for new drugs and potential label expansions for existing drugs into new indications (e.g., MASH, heart failure with preserved ejection fraction (HFpEF), kidney disease, Alzheimer's) could open substantial new market segments. Wegovy's CV risk reduction label is a prime example.  
• Long-Term Data and Real-World Evidence: As these drugs are used chronically, long-term safety and efficacy data, as well as real-world evidence on adherence and outcomes, will become increasingly important.
• Head-to-Head Comparisons: Direct comparative trials between leading agents could definitively establish relative efficacy and safety, influencing clinical guidelines and prescribing patterns.

The obesity market is highly dynamic and competitive. Sustained success will require continuous innovation, effective commercial execution, robust manufacturing capabilities, and skillful navigation of the evolving pricing and access landscape.

7. Conclusion and Strategic Outlook

Eli Lilly and Company is experiencing a period of exceptional growth, largely driven by the remarkable success of its incretin-based therapies, Mounjaro and Zepbound. The company has strategically positioned itself at the forefront of the metabolic disease space, challenging the long-standing leadership of Novo Nordisk. Lilly's substantial investments in R&D and manufacturing underscore its commitment to sustaining this momentum.

Orforglipron emerges as a highly anticipated and strategically vital asset in Lilly's portfolio. As a once-daily oral GLP-1 receptor agonist, it addresses a significant unmet need for convenient, effective obesity treatment. Clinical data suggests efficacy comparable to the highly successful injectable Wegovy, combined with a manageable safety profile consistent with the drug class. This combination of competitive efficacy and superior convenience positions orforglipron as a potential game-changer, capable of capturing significant market share and potentially expanding the overall treated population.

The successful realization of orforglipron's potential hinges on several key factors: confirmation of strong efficacy and safety in the forthcoming Phase 3 ATTAIN obesity trials, timely regulatory approvals worldwide, the implementation of a competitive pricing and market access strategy that balances value with affordability, and the execution of Lilly's ambitious manufacturing scale-up plans to ensure reliable supply.

The competitive landscape, primarily the duopoly with Novo Nordisk, will remain intense. However, Lilly's two-pronged approach with the highly efficacious Zepbound (injectable) and the convenient orforglipron (oral) provides a powerful combination to address diverse patient needs and preferences. This strategy is expected to drive continued market share gains for Lilly in the multi-billion dollar obesity market.

Looking forward, the market will continue to evolve rapidly, influenced by ongoing clinical developments, new competitive entries, pricing pressures, and payer decisions. Long-term data, potential label expansions into related comorbidities, and real-world evidence will further shape the landscape. Nonetheless, orforglipron represents a cornerstone of Eli Lilly's future growth strategy, possessing the potential to significantly reshape obesity treatment paradigms and deliver substantial long-term value for the company.

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