China’s Oral GLP-1 Surge: Rising Amid Global Setbacks and Intensifying Competition

Updated August 26, 2025: Added Eli Lilly’s ATTAIN-2 Phase III orforglipron results and August 20 VK2735 Phase II data.

The global race for oral GLP-1 receptor agonists—pill-based treatments for obesity, type 2 diabetes (T2D), and metabolic disorders—is accelerating, with China gaining critical momentum. While Pfizer has exited due to safety and tolerability issues and some candidates face mixed results, new readouts from Eli Lilly’s orforglipron and Viking’s VK2735 highlight both the promise and challenges of global development. Meanwhile, Chinese firms are rapidly scaling pipelines, armed with cost-effective small molecules, a massive domestic need, and increasing global credibility.

With a projected domestic market value of $558.5 million by 2030 (19% CAGR) and over 140 million Chinese living with diabetes, local innovation is being matched by aggressive investment and global partnerships. Over 25 oral GLP-1 assets are currently in development, positioning China as a serious challenger to Western incumbents like Novo Nordisk (oral semaglutide) and Eli Lilly (orforglipron).

Global Setbacks: Pharma Giants Recalibrate

Pfizer's Full Exit

Pfizer completed its exit from the oral GLP-1 field in August 2025 by discontinuing PF-06954522 due to poor Phase 1 data and intense competition. This followed the April 2025 halt of danuglipron over potential liver injury and tolerability issues (nausea, elevated enzymes), and the 2023 termination of lotiglipron for similar liver concerns, raising widespread safety worries for oral GLP-1 therapies.

Lilly’s Orforglipron: From Setback to Rebound

Eli Lilly’s orforglipron, a leading small-molecule oral GLP-1, first delivered 12.4% mean weight loss (27.3 lbs) in the ATTAIN-1 Phase 3 trial over 36 weeks (data cut August 5, 2025), meeting primary endpoints but lagging behind the 20%+ seen with injectables like Wegovy (20.9%) or Zepbound (22.5%). With a 25% nausea incidence (vs. 10% placebo), the shortfall triggered a 14.2% stock plunge on August 7, 2025, with analysts calling the results “moderate” and “less than transformative.”

However, the narrative shifted with ATTAIN-2, reported on August 26, 2025, in obese adults with Type 2 diabetes. At high dose, orforglipron achieved 10.5% mean weight loss (22.9 lbs) and ~1.8% A1C reduction, alongside improvements in blood pressure, lipids, and waist circumference. Crucially, all primary and key secondary endpoints were met, positioning Lilly to pursue global regulatory submissions in 2025–26. This restored investor confidence and reaffirmed orforglipron as Novo Nordisk’s key oral rival.

Novo Nordisk's Oral Semaglutide Progress

Novo Nordisk’s oral semaglutide 25 mg formulation is gaining traction, with OASIS 4 Phase 3 data showing a mean 16.6% weight loss over 52 weeks (vs. 2.7% for placebo) in patients with 78% adherence, per July 30, 2025, data. The company submitted a New Drug Application (NDA) to the U.S. FDA on August 1, 2025, with a PDUFA date set for December 15, 2025. Approval would pioneer oral GLP-1s for chronic weight management, bolstering Novo’s dominance.

Other Global Players in the Oral GLP-1 Race

Emerging players include Viking Therapeutics, with VK2735 (Phase 2 oral, up to 10.9% placebo-adjusted weight loss [12.2% absolute] at 13 weeks in topline VENTURE-Oral data, August 2025), and Roche’s CT-996 (Phase 1, 10% weight loss in a 4-week preclinical-to-human crossover, July 2025; Phase 2 planned Q1 2026), both poised to capitalize on gaps left by Pfizer and Lilly. However, VK2735's high discontinuation rates (up to 38% at top dose due to GI issues) led to a 37% stock drop, though analysts view the data as positive and outpacing competitors at similar timepoints, potentially advancing lower doses to Phase 3. Other contenders like Structure Therapeutics (Aleniglipron, GSBR-1290, Phase 2, 6.2% placebo-adjusted weight loss at 12 weeks, June 2024) and Gilead Sciences (GS-4571, Phase 2, 7.2% weight loss at 8 weeks, July 2025) contribute to the landscape, though their progress varies. This mix underscores a dynamic yet uneven global competition.

Oral GLP-1s: Pros and Trade-Offs

Why Oral Matters

• Needle-Free Delivery: Pills ease patient anxiety, improve adherence, and appeal to the treatment-naïve population.
• Manufacturing Advantage: Small molecules are ~50% cheaper to produce than peptides and easier to scale, opening new frontiers in emerging markets.
• Distribution Efficiency: Oral tablets bypass the cold-chain complexities of injectables.

Challenges Remain

• Bioavailability: Oral GLP-1s must survive gastrointestinal degradation, often needing advanced delivery technologies (e.g., SNAC or novel enhancers).
• Side Effects: Higher doses can exacerbate nausea and GI upset, as seen with orforglipron and danuglipron.
• Lower Potency: Weight loss efficacy typically lags behind injectable GLP-1s (12–13% vs. 15–20%).
• High-Dose Viability: Oral peptides like Novo’s 25 mg semaglutide or Viking’s higher VK2735 doses raise manufacturing scalability and cost concerns, though Novo assures capacity; small molecules (e.g., orforglipron) offer advantages but may underperform clinically.

China’s Strategy: Scale, Speed, and Global Ambition

China is capitalizing on its strengths:

• Lower R&D and trial costs
• A massive patient pool
• Fast-tracked regulatory channels
• Prolific licensing partnerships

Chinese oral GLP-1s, primarily non-peptidic small molecules, boast superior shelf-life, ease of dosing, and attractive economics for both local and global markets. Several assets have entered Phase 3, with commercial launches expected as early as 2026–2027.

Key Global Collaborations

• Hansoh Pharma & Merck (Dec 2024): Merck licensed HS-10535, a long-acting oral GLP-1, in a deal worth up to $2 billion, marking one of the largest Sino-Western obesity partnerships to date. Merck handles global development; Hansoh retains China rights.
• AstraZeneca & Eccogene: Co-developing ECC5004 (AZD5004), an oral GLP-1 for obesity/T2D with promising bioavailability. Entered Phase 1b in 2025.
• CSPC & Madrigal Pharma: In July 2025, Madrigal licensed SYH2086, a preclinical oral GLP-1 derivative of orforglipron, for up to $2 billion, reflecting continued Western appetite for Chinese innovation.

Chinese Oral GLP-1 Assets in Development

Non-Chinese Oral GLP-1 Assets in Development

 Conclusion and Outlook

China’s oral GLP-1 pipeline, led by Hansoh, Huadong, and Innovent, positions it as a global leader, leveraging cost advantages and a vast patient pool. Assets like HRS-7535 and HDM1002 demonstrate competitive weight loss (up to 9.5%) and favorable safety, leveraging China’s vast patient pool and streamlined development. However, oral GLP-1s face ongoing challenges, including gastrointestinal side effects (e.g., high discontinuations in Viking’s VK2735 and Pfizer’s danuglipron) and safety concerns (e.g., liver toxicity in Pfizer’s danuglipron and lotiglipron), lower potency compared to injectables, and high-dose manufacturing viability (e.g., Novo’s 25 mg semaglutide). Future success hinges on optimizing bioavailability, tolerability, and scalability.

Global developments reflect both setbacks and rebounds: Pfizer’s termination of danuglipron and lotiglipron due to safety/tolerability, Viking’s VK2735 tolerability concerns, and Eli Lilly’s orforglipron showing a weaker ATTAIN-1 readout but stronger ATTAIN-2 results in T2D patients (10.5% weight loss, 1.8% HbA1c reduction). Together, these underline the multifaceted hurdles in oral GLP-1 development. China’s streamlined regulatory pathways and robust pipeline position it to overcome these obstacles, potentially leading the market by 2030, with projections estimating a $558.5 million GLP-1 market (GlobalData, 2025).

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