Eli Lilly's Oforlipron: A Game-Changing Oral GLP-1 That Could Topple Novo Nordisk's Dominance

The global GLP-1 market, valued at $49.3 billion in 2024, is poised for explosive growth, projected to reach $157.5 billion by 2035 as obesity and type 2 diabetes rates soar. Yet, this growth is far from evenly distributed. Eli Lilly's new oral GLP-1 receptor agonist, orforglipron, has emerged as a disruptor with the potential to upend the dominance of Novo Nordisk, whose flagship drug Ozempic currently commands a 62% market share but faces mounting headwinds.



### Why Oforlipron Stands Out: The Oral Edge Over Injections
The GLP-1 class has long been dominated by injectable therapies like Ozempic and Wegovy, which require weekly or daily injections to mimic the body's natural GLP-1 hormone. Oforlipron breaks this mold as the first oral small-molecule GLP-1 agonist that doesn't need special delivery systems (e.g., capsules with absorption enhancers like in semaglutide). This simplicity offers two critical advantages:
1. Convenience: Patients can take it once daily without food or water restrictions, addressing a major drawback of existing therapies.
2. Cost Efficiency: Oral formulations typically have lower production costs than injectables, potentially enabling broader access and faster adoption.

### Phase 3 Trial Results: A Clinician's Dream
The Phase 3 ACHIEVE-1 trial, completed in early 2025, delivered stellar results that validate Oforlipron's efficacy:
- A1C Reduction: At the 12mg dose—the sweet spot for efficacy—the drug reduced A1C levels by 1.6% over 40 weeks, outperforming placebo (0.1%) and rivaling injectable therapies.
- Weight Loss: The highest dose (36mg) induced an average 16 lb loss (7.9% of body weight), a figure competitive with Wegovy (14.3 lb average) but achieved without the need for injections.
- Safety Profile: While gastrointestinal side effects (nausea, diarrhea) were common, no serious liver issues emerged—a critical advantage over Pfizer's danuglipron, which was shelved due to hepatic toxicity.



### The Addressable Market: Billions Up for Grabs
With 536.6 million people worldwide living with type 2 diabetes (projected to rise to 783 million by 2045) and 1.9 billion obese individuals, Oforlipron's dual targeting of both conditions opens vast opportunities:
- Diabetes: Oforlipron's A1C reductions (up to 1.6%) rival Novo's Victoza (1.5%) and Lilly's own Mounjaro (1.7%).
- Obesity: At 16 lb weight loss, it matches Wegovy's performance but avoids the logistical and cost barriers of injections.

The $31.27 billion obesity drug market alone is growing at 19.2% CAGR, making Oforlipron's oral form a must-have for patients and insurers alike.

### Why Novo Nordisk's Dominance Is Wobbling
Despite its current 62% market share, Novo faces three existential threats:
1. Generic Competition: Compounded versions of semaglutide (Ozempic/Wegovy) have eroded sales, forcing Novo to cut 2025 sales growth guidance to 13–21% from 16–24%.
2. Slowing Growth: Ozempic's sales grew just 3.8% in Q2 2025, signaling peak adoption.
3. Pipeline Lag: Novo's next-gen GLP-1/GIP combo, CagriSema, trails Lilly's retatrutide (24% weight loss in trials) and faces a delayed FDA submission.

Oforlipron's oral formulation and safety profile could accelerate this decline.

### Analysts See Peak Sales Surpassing $40 Billion
Analysts are bullish on Oforlipron's potential:
- Jefferies raised its peak sales estimate to $43 billion (up 10% from $39 billion) after the Phase 3 results, citing its “best-in-class” profile.
- Morningstar upgraded Eli Lilly's fair value, noting Oforlipron could add $10 billion in annual sales by 2030.



### Investment Thesis: Buy LLY Now—The Upside Is Clear
Eli Lilly's stock (LLY) currently trades at a P/E of 24, below its five-year average of 29 and far below Novo's 42. This undervaluation ignores Oforlipron's transformative potential:
- Regulatory Momentum: LLY plans to submit Oforlipron for obesity approval by end-2025 and diabetes by 2026, with FDA decisions likely in 2026–2027.
- Inventory Buildup: LLY has stockpiled $548 million in pre-launch inventory, signaling confidence in rapid adoption.

The risks? Competition and pricing pressures exist, but Oforlipron's oral convenience and safety profile create a durable moat.

### Final Take
Oforlipron isn't just another diabetes drug—it's a category killer that could redefine the GLP-1 market. With Novo's growth stalling and Lilly's pipeline firing on all cylinders (including retatrutide and Oforlipron), now is the time to buy LLY. Analysts' $43 billion peak sales target implies upside of 50–70% from current levels. In a sector where GLP-1s are the “new penicillin,” Lilly is primed to win big.



Recommendation: Buy LLY with a 12-month price target of $450 (vs. $320 current price). The next catalyst—FDA submissions by year-end—could spark a rerating.