GLP-1 Demand: What it means for peptide manufacturers

GLP-1 receptor agonists are transforming peptide manufacturing. For decades, peptide APIs were typically produced at kilogram scale for relatively small patient populations. Manufacturing focused primarily on solving complex chemistry challenges rather than managing industrial throughput. GLP-1 therapies are fundamentally different.

Drugs targeting diabetes, obesity, and related metabolic diseases are taken chronically by very large patient populations. As a result, demand for these APIs is no longer measured in kilograms but increasingly in multi-kilograms and metric tons.

At the same time, multiple blockbuster GLP-1 therapies are already on the market (Ozempic, Wegovy, and Mounjaro), with numerous next-generation analogues and combination incretin therapies currently in development. The result is unprecedented pressure on global peptide manufacturing capacity.

For peptide manufacturers and GLP-1 CMOs and CDMOs, this creates a new challenge: scaling complex peptide synthesis while maintaining the purity, consistency, and cost efficiency expected for commercial APIs. Meeting GLP-1 demand requires a shift in thinking – from managing individual peptide projects to building industrialized manufacturing platforms capable of sustained, large-scale production.

How GLP-1 demand changes the manufacturing brief

Peptide manufacturing typically scales gradually throughout development:

• Discovery: milligrams to grams
• Clinical development: kilograms
• Commercial supply: multi-kilogram campaigns

For many historical peptide drugs, that final step remained manageable within existing manufacturing infrastructure. GLP-1 therapies have dramatically expanded that scale.

Commercial demand for these APIs can reach tens or even hundreds of kilograms annually, and in some cases may approach metric-ton production levels. Supporting this level of demand requires more than simply increasing batch size.

Manufacturers must have access to:

• Large-capacity SPPS reactors
• Scalable purification infrastructure
• Sufficient freeze-drying capacity
• Reliable supply chains for key raw materials

Those raw materials include:

• Protected amino acids
• Solid-phase resins
• Solvents
• Fatty-acid side chains and other modifiers

At these volumes, process efficiency becomes a primary driver of manufacturing capacity and cost.

New operational pressures for peptide CDMOs

Compared with traditional peptide APIs, GLP-1 programs introduce several new operational pressures.

Throughput and equipment utilization

GLP-1 programs often require repeated large-scale campaigns. Without efficient processes, reactors, purification columns, and lyophilizers can quickly become bottlenecks.

Impurity control at scale

Long peptides with chemical modifications can generate closely related impurities. Maintaining consistent impurity profiles across scale-ups and sites becomes critical for regulatory compliance and product quality.

Sustainability

Solid-phase peptide synthesis (SPPS) requires significant solvent volumes. As GLP-1 production expands, solvent consumption and waste management become increasingly important considerations.

Capital investment

Facilities capable of multi-kilo and metric-ton peptide production require substantial investment in SPPS equipment, purification systems, and downstream infrastructure.

Together, these pressures are accelerating the shift toward specialized CMOs and CDMOs with large-scale manufacturing platforms. Bachem has decades of peptide synthesis expertise and has invested in high-capacity production facilities to support the rapidly growing demand.

GLP-1 manufacturing process basics

Most GLP-1 receptor agonists are produced using SPPS.

Although the core process is well established, GLP-1 peptides place additional demands on manufacturing systems due to their length and chemical modifications.

A simplified GLP-1 manufacturing process typically includes the following stages:

Solid-phase peptide synthesis (SPPS)

The peptide chain is assembled sequentially on a solid resin through repeated cycles of:

• Deprotection
• Amino-acid coupling
• Washing

Cleavage and crude isolation

Following synthesis, the peptide is cleaved from the resin and precipitated to isolate crude material.

Purification

Achieving pharmaceutical purity typically requires multi-dimensional chromatography to remove sequence variants and other impurities.

Final isolation and lyophilization

The purified peptide is isolated and freeze-dried to produce the final API.

Each stage must scale efficiently to support large commercial production campaigns.

Why GLP-1 peptides can stress SPPS

Several characteristics of GLP-1 receptor agonists can make them particularly challenging to manufacture.

Long sequences

Many GLP-1 analogues contain 30–40 amino acids or more. In SPPS, overall yield declines as the number of coupling cycles increases.

 Chemical modifications

Fatty-acid side chains and other structural modifications can complicate both synthesis and downstream purification.

Sensitivity to coupling efficiency

Even small improvements in per-cycle SPPS yield can dramatically increase total process yield when multiplied across dozens of synthesis cycles.

These challenges have led many manufacturers to explore fragment-based synthesis strategies for long peptides.

However, fragment synthesis is not always the optimal solution.

Linear vs fragment SPPS for GLP-1 peptides

Fragment-based synthesis approaches divide a long peptide into smaller segments that are synthesized separately and then joined through a conjugation step. In theory, shorter fragments can be produced with higher yields.

However, fragment strategies introduce additional operations, including:

• Soft cleavage of fragments
• Conjugation reactions
• Additional analytical development

Fragment conjugation can also introduce epimerization , producing stereoisomers that may be difficult to remove during purification.

Because of these trade-offs, the optimal strategy depends strongly on the specific molecule and manufacturing conditions.

In a recent evaluation of a representative GLP-1 receptor agonist, we compared optimized linear SPPS with fragment-based routes under realistic manufacturing assumptions.

The study highlighted an important finding:

At high per-cycle SPPS yields, linear synthesis can outperform fragment-based approaches, delivering higher overall yields, and simpler, more cost efficient manufacturing processes.

This does not mean fragment synthesis is ineffective. For very long peptides or molecules with favorable conjugation sites, fragment approaches may still offer advantages.

However, the results demonstrate that high-efficiency linear SPPS remains highly competitive for GLP-1-like peptides.

For a deeper discussion of the study design and findings, see our full GLP-1 receptor agonist feasibility study on linear vs fragment SPPS.

What it takes to keep up with GLP-1 demand

As GLP-1 therapies scale globally, peptide manufacturers must move towards GLP-1 peptide manufacturing capabilities that focus on:

• High and consistent SPPS cycle efficiency
• Scalable purification strategies
• Standardized process development workflows
• Robust raw-material supply chains

This approach supports faster development timelines, more predictable scale-ups, and more efficient use of manufacturing infrastructure.

Sponsors evaluating a GLP-1 CDMO increasingly look for partners that combine:

• Large-scale SPPS infrastructure
• Advanced purification capabilities
• Deep process development expertise
• Strong analytical and impurity characterization capabilities

Together, these capabilities enable reliable production of long, modified peptides at commercial scale.

Strategic questions for GLP-1 manufacturing

For companies developing GLP-1 therapies, manufacturing strategy is becoming a critical early decision. Making informed decisions up front can reduce risk, improve efficiency, and help ensure a smooth path to commercialization.

Key questions usually include route and molecule strategy, the ability to scale SPPS and downstream operations to industrial volumes, and the long‑term sustainability of the manufacturing process and supply chain.

Answering these questions early can significantly reduce manufacturing risk. Partnering with an experienced CDMO like Bachem can help navigate these considerations efficiently, leveraging established peptide synthesis platforms and large-scale capabilities.

Final thoughts and how Bachem can help

GLP-1 therapies are reshaping the peptide industry.

Demand for these drugs is pushing peptide manufacturing toward industrial-scale production, requiring efficient processes, robust infrastructure, and data-driven route selection.

As our recent feasibility work shows, fragment approaches are not automatically superior for long peptides. For many GLP-1-like molecules, optimized linear SPPS can deliver strong yields, scalable processes, and lower operational complexity.

For developers navigating GLP-1 manufacturing strategy, the most reliable approach remains a molecule-specific assessment that evaluates process options under realistic production conditions.

If you are planning a GLP-1 program or evaluating manufacturing routes, Bachem provides integrated peptide CDMO and CMO support – from process development and analytical characterization to large-scale GMP manufacturing of peptide APIs.

With decades of expertise in solid-phase peptide synthesis and industrial-scale production infrastructure, Bachem helps pharmaceutical and biotech partners develop scalable processes that support both clinical development and long-term commercial supply.

Contact Bachem today to learn how we can help.