As the global weight loss drug market continues to expand rapidly, GLP-1 drugs have become one of the most closely watched sectors in the pharmaceutical industry in recent years.

From once-weekly injections to the rapid development of once-monthly and even longer dosing intervals, ultra-long-acting GLP-1 technologies are reshaping the global diabetes and obesity treatment landscape.

Centered around technologies such as fatty acid modification, antibody conjugation, subcutaneous depot sustained-release systems, and peptide stapling, a new wave of competition in the ultra-long-acting GLP-1 era has fully begun.

For the global pharmaceutical industry, this not only represents a shift in drug development strategies, but also signals new growth opportunities for GLP-1 supply chains, peptide APIs, cold-chain transportation, and pharmaceutical distribution systems.

As a global pharmaceutical distributor focused on innovative drug supply chains and peptide therapeutics trends, DengYueMed is also closely monitoring the development opportunities surrounding ultra-long-acting GLP-1 technologies, peptide raw materials, and international pharmaceutical distribution markets.

Why Are GLP-1 Drugs Moving Toward Ultra-Long-Acting Therapies?

Although current mainstream GLP-1 drugs have achieved tremendous success, several major industry-wide challenges still remain:

● High dosing frequency

● Poor long-term patient adherence

● Significant gastrointestinal side effects

● Growing global manufacturing and supply chain pressure

● High cold-chain transportation and commercialization costs

Especially in obesity treatment, patients often require long-term or even lifelong therapy. Frequent injections can directly affect treatment retention and long-term adherence.

As a result, reducing dosing frequency has become one of the most important technological directions for next-generation GLP-1 therapies.

The core goal of ultra-long-acting delivery technologies is to extend drug half-life and achieve controlled sustained release, enabling:

● Once every two weeks dosing

● Once monthly dosing

● Even longer dosing intervals

This approach not only improves the patient experience, but also enhances the commercial value of GLP-1 therapies.

The Major Technology Platforms Behind Ultra-Long-Acting GLP-1 Drugs

Currently, global ultra-long-acting GLP-1 development is mainly focused on four major technology platforms:

1.  Fatty acid terminal modification technology

2.  Antibody conjugation technology

3.  Subcutaneous depot sustained-release technology

4.  Peptide stapling technology

Major international pharmaceutical companies including Pfizer, Eli Lilly and Company, Novo Nordisk, and Amgen, along with multiple Chinese biotech companies, are actively investing in these technologies.

MET-097i: A Representative of Fatty Acid Terminal Modification Technology

In 2025, Pfizer completed its $9.2 billion acquisition of Metsera, attracting significant industry attention.

The key reason behind the acquisition was Metsera’s ultra-long-acting HALO platform.

The HALO platform modifies peptide drug terminals with fatty acid chains, enabling strong yet reversible binding to plasma albumin, significantly extending circulation time in the human body.

Under this platform, MET-097i achieved an approximately 380-hour half-life, supporting once-monthly dosing.

Key Advantages of MET-097i

1. Ultra-Long Half-Life

Compared with traditional once-weekly GLP-1 injections, MET-097i significantly reduces dosing frequency.

2. Sustained Weight Loss Effects

Clinical data showed:

● Weight reduction effects lasting at least 8 weeks

● 14.1% weight reduction at 28 weeks in Phase IIb trials

● Weight loss efficacy approaching that of dual agonists

3. Strong Platform Scalability

The HALO platform is not limited to injectable therapies and is also advancing:

● Long-acting amylin analogs

● Oral GLP-1 therapies

● Multi-target metabolic drugs

This suggests that monthly GLP-1 formulations may only be the beginning.

AMG133: Antibody Conjugation Technology Enters Phase III

Developed by Amgen, AMG133 is currently one of the most closely watched ultra-long-acting GLP-1 candidates globally.

AMG133 combines:

● GIPR antibodies

● GLP-1 receptor agonists

into a dual-mechanism design.

Its core strategy is to leverage the long circulation time of antibodies to prolong therapeutic activity.

What Makes AMG133 Stand Out?

1. Half-Life of Approximately 21 Days

Compared with conventional weekly GLP-1 drugs, AMG133 enables much lower dosing frequency.

2. Highly Competitive Weight Loss Results

Phase II clinical data demonstrated:

● Up to 19.9% weight reduction in obese patients

● Up to 17% weight reduction in obese patients with diabetes

● Weight loss effects maintained for up to 150 days after the final dose

This indicates that the GLP-1 market may shift from “frequent long-term dosing” toward “low-frequency, high-efficiency treatment.”

CAM2056: Subcutaneous Depot Sustained-Release Technology Is Emerging

In addition to directly extending drug half-life, another important technological direction is the creation of a “drug depot” under the skin.

Among these platforms, Camurus and its FluidCrystal technology are among the most representative.

How FluidCrystal Technology Works

After injection, the drug forms a stable liquid crystal depot beneath the skin.

The drug is then released slowly over time, helping to:

● Sustain stable plasma drug concentrations

● Reduce peak-to-trough fluctuations

● Improve overall drug tolerability

This mechanism may significantly improve GLP-1 treatment tolerability.

The Market Potential of CAM2056

CAM2056 is a once-monthly semaglutide formulation currently in Phase I clinical development.

If future clinical data remain positive, its commercial potential could be substantial because:

● Novo Nordisk already has a massive Wegovy user base

● Monthly dosing may significantly improve patient adherence

● Long-term treatment costs could potentially be reduced

Meanwhile, Ascendis Pharma has also licensed its TransCon technology to Novo Nordisk for long-acting GLP-1 development.

Chinese Companies Are Rapidly Catching Up

China’s GLP-1 sector is gradually transitioning from a “follower” to an “innovation-driven” market.

Ascletis Pharma: ULAP Subcutaneous Depot Platform

Ascletis Pharma developed ASC30, whose subcutaneous formulation achieved a half-life of up to 36 days.

Its goals include:

● Once-monthly dosing

● Reduced gastrointestinal side effects

● Improved long-term adherence in obesity treatment

The first participants have already been dosed in its U.S. Phase IIa clinical trial.

RAY1225: Peptide Stapling Becomes a Key Chinese Innovation Direction

Peptide stapling technology has become another rapidly developing pathway among Chinese pharmaceutical companies.

Its core principle is to enhance peptide stability through stapled molecular structures, reducing degradation and inactivation.

Clinical Performance of RAY1225

Developed by Zhongsheng Pharmaceutical, RAY1225 is a dual GIP/GLP-1 receptor agonist.

Its features include:

● Approximately double the half-life of tirzepatide

● Potential for once-every-two-weeks dosing

● Relatively milder gastrointestinal side effects

Phase II clinical data showed:

● More than 10% average weight reduction after 10 weeks

● Over 15% weight reduction in the 9 mg group at 24 weeks

● More than 95% of participants achieved at least 5% weight loss

These results suggest that Chinese GLP-1 innovations are beginning to gain global competitiveness.

In addition, Tonghua Dongbao has also advanced THDBH120 into Phase II clinical development.

How Will Ultra-Long-Acting GLP-1 Drugs Transform the Industry?

The impact of ultra-long-acting GLP-1 therapies extends far beyond the drugs themselves.

The entire pharmaceutical industry chain may be reshaped.

1. Growing Demand for Peptide APIs

With:

● Expanding GLP-1 manufacturing capacity

● Wider adoption of long-term treatment

● Increasing development of multi-target therapies

the market demand for high-quality peptide raw materials is expected to continue growing.

In particular, demand may surge for:

● High-purity peptide APIs

● Long-acting modified peptide materials

● Conjugation-related intermediates

2. Upgrading Cold Chain and Pharmaceutical Transportation Systems

Although ultra-long-acting GLP-1 therapies reduce injection frequency, they also place higher requirements on:

● Stability

● Temperature control

● Long-distance transportation

For global pharmaceutical distributors, ensuring:

● Peptide stability

● Cold-chain continuity

● Internationally compliant transportation

will become a key competitive advantage.

3. The Future May Enter the “Quarterly Injection” Era

The current industry focus is on:

● Monthly formulations

● Bi-monthly formulations

However, based on technological evolution, future therapies may potentially achieve:

● Quarterly dosing

● Even semi-annual dosing

If realized, this could fundamentally transform chronic disease treatment models.

Conclusion

In the past, competition in the GLP-1 market mainly focused on:

● Who delivers stronger weight loss

● Who achieves better glucose control

Today, the industry focus has shifted toward:

● Longer duration

● Lower dosing frequency

● Better patient adherence

● More advanced platform technologies

From Metsera’s HALO platform, to Amgen’s antibody conjugation approach, to Camurus’ sustained-release technology, and the peptide stapling innovations emerging from Chinese companies, the GLP-1 market is officially entering the ultra-long-acting era.

Over the coming years, as ultra-long-acting technologies continue to mature, GLP-1 drugs are expected not only to further transform obesity and diabetes treatment, but also to drive new growth opportunities across peptide APIs, cold-chain logistics, pharmaceutical distribution, and advanced drug delivery systems.

As a global pharmaceutical distributor focused on innovative drug circulation, peptide raw materials, and international pharmaceutical supply chains, DengYueMed will continue monitoring the future development of ultra-long-acting GLP-1 technologies and the new opportunities emerging in the global weight loss drug market.