The GLP-1 Supply Chain Explained: How the Shortage Happened, What Fixed It, What Compounding Did

Trust signals

> Reviewed by FormBlends Medical Team · Last updated May 2026 · 12 sources cited

Key Takeaways

• The 2022 through early 2025 GLP-1 shortages were driven by fill-finish capacity, not active ingredient supply or raw material constraints.
• Tirzepatide returned to the FDA shortage list resolution on October 2, 2024; semaglutide on February 21, 2025.
• Compounding under FDCA section 503A expanded substantially during the shortage and contracted equally substantially after resolution.
• The two-manufacturer market structure (Novo Nordisk and Eli Lilly) creates concentration risk that future demand growth could expose again.
• Understanding the supply chain helps separate transient pharmacy-level stock-outs from broader national shortages and clarifies why compounded products are not interchangeable with brand-name medications.

Direct answer

GLP-1 shortages between 2022 and 2025 happened because demand for diabetes and obesity prescribing grew faster than fill-finish capacity could expand. The bottleneck was assembling sterile prefilled pens at scale, not making the active ingredient. Novo Nordisk and Eli Lilly invested heavily in new fill-finish capacity, with Eli Lilly's expansion outpacing Novo Nordisk's by several months. Compounded semaglutide and tirzepatide filled some of the unmet demand during the shortage under FDCA section 503A, then contracted when the FDA resolved the shortages.

Table of contents

1. What a GLP-1 actually is, manufacturing-wise
2. The supply chain in eight steps
3. Where the bottleneck was
4. The four forces that drove demand beyond capacity
5. How manufacturers expanded
6. What FDCA 503A compounding actually does
7. The compounding wind-down after shortage resolution
8. Why concentration in two manufacturers matters
9. What another GLP-1 shortage could look like
10. FAQ
11. Sources

What a GLP-1 actually is, manufacturing-wise

The two dominant GLP-1 medications, semaglutide and tirzepatide, are large modified peptides. Each is around 39 to 40 amino acids long with chemical modifications that include a fatty-acid linker designed to bind reversibly to albumin and prolong the half-life. Tirzepatide includes structural elements that activate both the GIP and GLP-1 receptors; semaglutide activates the GLP-1 receptor alone.

This molecular complexity matters for manufacturing.

• Producing the peptide backbone requires recombinant expression in microorganisms (typically Saccharomyces cerevisiae yeast for semaglutide).
• Chemical synthesis or semi-synthesis adds modifications that native fermentation cannot produce directly.
• Purification requires multiple chromatography steps to remove process-related impurities.
• Final formulation requires balancing solubility, stability, and tolerability in an injectable form.
• Sterile filling and pen assembly require aseptic processing.

None of these steps is unique to GLP-1s, but together they make the production timeline measurably longer than for small-molecule pills.

The supply chain in eight steps

1. Fermentation. Genetically modified yeast produces the peptide precursor.
2. Chemical modification. The precursor is modified to add the fatty-acid linker and any remaining structural changes.
3. Purification. Multiple chromatography steps remove impurities and concentrate the drug substance.
4. Drug substance release. Quality testing confirms purity, potency, and identity. The drug substance is then shipped to fill-finish facilities.
5. Formulation. Drug substance is combined with excipients to produce the final liquid formulation.
6. Aseptic filling. The formulation is filled into sterile cartridges or vials in a Grade A clean room.
7. Device assembly and labeling. Cartridges are assembled into prefilled pen devices, tested, labeled, and packaged.
8. Distribution. Finished product moves through authorized wholesalers to pharmacies under cold-chain conditions.

Each step is conducted under cGMP regulations. Each is documented and traceable. Disruption at any single step can cascade through to patient access.

Where the bottleneck was

During 2022 through 2024, the consistent bottleneck across manufacturers was step 6 (aseptic filling) and step 7 (device assembly), collectively known as fill-finish.

Reasons fill-finish is hard to scale:

• Aseptic filling lines for injectable biologics require specialized equipment that has long lead times for procurement.
• Each line must be qualified through equipment installation qualification, operational qualification, and performance qualification.
• Each new product on a line requires process validation runs.
• FDA pre-approval inspection of the line is required before commercial production.
• Each line typically produces a narrow range of pen configurations; switching configurations requires changeover time.

The result: announcing a new fill-finish facility in 2022 typically means commercial production in 2025 or 2026, not the next quarter.

The four forces that drove demand beyond capacity

The supply-demand mismatch resulted from a confluence of factors.

Force 1: New indication approvals. Wegovy (June 2021) and Zepbound (November 2023) added obesity indications to molecules previously prescribed primarily for diabetes. Each new indication make availableed a substantially larger patient population.

Force 2: Off-label prescribing. Ozempic was widely prescribed off-label for weight loss before Wegovy supply caught up. Mounjaro was prescribed off-label before Zepbound launched. Off-label prescribing channeled diabetes-indication supply into weight-loss demand.

Force 3: Cardiovascular outcomes data. The SELECT trial (Lincoff et al., NEJM, 2023) demonstrated cardiovascular benefit of semaglutide in patients with cardiovascular disease and overweight or obesity but without diabetes. This data expanded the clinical rationale for prescribing and pulled payers toward broader coverage.

Force 4: Social-media amplification. GLP-1 medications became culturally salient through TikTok, Twitter, and traditional media coverage in 2022 and 2023. Awareness expanded the pool of patients seeking prescriptions, including patients outside the FDA-approved indications.

Capacity could not scale on the same timeline as any of these forces.

How manufacturers expanded

Both Novo Nordisk and Eli Lilly responded with substantial capital investment.

Novo Nordisk:

• Multibillion-dollar expansions at Kalundborg (Denmark) and Chartres (France).
• Significant fill-finish expansion at Clayton (North Carolina).
• Acquisition of Catalent (via Novo Holdings) completed in late 2024, adding contract fill-finish capacity.

Eli Lilly:

• New large-scale injectable manufacturing facility in Concord, North Carolina, opened during 2023.
• Substantial API expansion in Ireland (Limerick and Kinsale).
• Build-out of Lebanon, Indiana, for additional capacity through the second half of the decade.
• Addition of Branchburg, New Jersey, fill-finish through acquisition.

By late 2024, Eli Lilly's expanded capacity allowed the FDA to resolve the tirzepatide shortage. By early 2025, Novo Nordisk's expanded capacity allowed resolution of the semaglutide shortage.

What FDCA 503A compounding actually does

Section 503A of the Federal Food, Drug, and Cosmetic Act allows state-licensed pharmacists to compound drugs for individual patients under specific conditions. One of those conditions is the FDA Drug Shortages list: when a drug is on the shortage list, the prohibition on compounding "essentially a copy of a commercially available drug" is set aside.

During the GLP-1 shortages:

• State-licensed compounding pharmacies could prepare semaglutide and tirzepatide formulations for patients with valid prescriptions.
• Telehealth platforms partnered with 503A compounding pharmacies to deliver compounded GLP-1s to patients.
• Compounded versions were typically less expensive than the brand-name products, even on a cash-pay basis.
• Compounded products were not FDA-approved and were not interchangeable with the brand-name products.

503B outsourcing facilities, which can compound under different rules and at larger scale, were a separate category subject to additional restrictions during this period.

The compounding wind-down after shortage resolution

When the FDA removed tirzepatide from the shortage list in October 2024 and semaglutide in February 2025, the shortage-list basis for compounding evaporated. Several consequences followed.

• The FDA issued transition guidance specifying timelines for compounding pharmacies to wind down operations.
• Eli Lilly and Novo Nordisk both intensified litigation against compounders, telehealth platforms, and medical spas marketing compounded GLP-1 products in ways that the manufacturers alleged exceeded permissible compounding.
• Many telehealth platforms either transitioned to brand-name products, switched to other compounded therapies, or wound down their GLP-1 offerings.
• Patients who had been on compounded GLP-1s either transitioned to brand-name therapy, switched molecules, or discontinued treatment.

By May 2026, the broad compounded GLP-1 market that existed during the shortage no longer operates at the same scale. Narrow patient-specific compounding remains possible only for documented clinical needs.

Why concentration in two manufacturers matters

The US GLP-1 supply rests almost entirely on Novo Nordisk and Eli Lilly. That concentration has implications.

Implication 1: Single-point disruptions cascade. A regulatory finding, manufacturing incident, or supply-chain shock at either company affects national supply.

Implication 2: Pricing power. Two-company markets typically support higher prices than competitive markets. US list prices for GLP-1s reflect this dynamic.

Implication 3: Patent extension protects concentration. Both companies hold patents that extend into the 2030s in major markets. Biosimilar competition is years away.

Implication 4: Demand growth has nowhere else to flow. If demand exceeds the combined capacity of the two manufacturers, the system has no alternative supply at scale.

Diversification through additional approved competitors (such as eventual oral GLP-1s from other manufacturers, biosimilars after patent expiration, or new molecules in development) could change this picture over time.

What another GLP-1 shortage could look like

Future shortage risk depends on several variables.

Trigger	Likelihood (qualitative)	Likely effect
New indication approval that materially expands eligible population	Moderate	Demand surge over several quarters
Payer coverage expansion (e.g., broader Medicare Part D)	Moderate	Rapid demand growth
Manufacturing site disruption	Low to moderate	Regional or national constraint
FDA inspection finding	Low	Temporary production pause
International demand growth pulling US-bound supply	Low to moderate	Slower US replenishment
Geopolitical disruption to logistics	Low	Timing-driven local shortages

None of these are predicted. Each is plausible enough to monitor.

The contrary view: why the shortage might have been overstated

For balance, the strongest argument against treating the 2022 to 2025 GLP-1 shortage as a public health crisis.

The argument runs:

• FDA shortage status is a regulatory classification, not a public-health emergency. Patients who genuinely needed the medication for FDA-approved indications generally retained access through clinician advocacy, pharmacy transfers, and dose substitution.
• Much of the demand pressure came from off-label and out-of-criteria prescribing, which the shortage indirectly constrained.
• The shortage period coincided with maturation of clinical evidence (SELECT trial, SURMOUNT outcomes) that justified continued investment, even at high cost.
• Compounding filled gaps where demand exceeded supply, though with quality and oversight trade-offs.
• The pharmaceutical supply chain ultimately responded with multibillion-dollar capacity expansion that should support a larger eligible population going forward.

None of this excuses pharmacy-level scarcity for patients with diabetes who could not fill their prescriptions during peak shortage periods. But it suggests the system worked, slowly, to scale supply to demand, and that the headline narrative of constant crisis oversimplified.

FAQ

Why did GLP-1 medications run into shortage?

Demand grew faster than fill-finish capacity. The active ingredient was generally available; pen assembly was the limiting step.

When did the GLP-1 shortages end?

Tirzepatide on October 2, 2024. Semaglutide on February 21, 2025.

What is fill-finish?

The late stages of pharmaceutical production where drug substance is filled into sterile containers, assembled into delivery devices, labeled, and packaged.

What does FDCA section 503A do?

It allows state-licensed pharmacists to compound drugs for individual patients under specific conditions, including when a drug is on the FDA shortage list.

Did compounding cause quality problems?

Most state-licensed compounding pharmacies operated within their regulatory frameworks. The FDA did identify problematic products (counterfeit, non-pharmacopeial sources of active ingredient, mislabeled products) that traded on the compounding market during the shortage.

Can I still get compounded semaglutide or tirzepatide?

Broad shortage-tolerance compounding has wound down. Patient-specific compounding remains possible only in narrow circumstances. Discuss with your clinician and pharmacy.

Is the supply chain robust now?

More robust than in 2023 but still concentrated in two manufacturers. Future demand shocks could re-expose capacity limits.

Will biosimilars eventually compete?

Patent protection on semaglutide and tirzepatide extends into the 2030s in major markets. Biosimilar competition is a longer-horizon question.

Related guides

• Where Is Ozempic Manufactured? Mapping Novo Nordisk's Global Supply Chain
• Is There an Ozempic Shortage in 2026? The Current Supply Picture
• Is There a Zepbound Shortage in 2026? Where Tirzepatide Supply Stands
• 503A vs 503B Compounding Pharmacy: Key Differences Explained for 2026
• How Compounding Pharmacies Make Peptides: Process Explained for 2026

Sources

1. US Food and Drug Administration. Drug Shortages Database. Semaglutide injection resolution, February 21, 2025; Tirzepatide injection resolution, October 2, 2024.
2. Federal Food, Drug, and Cosmetic Act. Section 503A.
3. FDA. Guidance for Industry: Compounding Animal and Human Drugs Under Section 503A. Current edition.
4. Novo Nordisk A/S. Annual Report 2024. Capacity expansion disclosures.
5. Eli Lilly and Company. 2024 Annual Report on Form 10-K. Manufacturing disclosures.
6. Wilding JPH, Batterham RL, Calanna S, et al. Once-Weekly Semaglutide in Adults with Overweight or Obesity (STEP 1). New England Journal of Medicine. 2021.
7. Jastreboff AM, Aronne LJ, Ahmad NN, et al. Tirzepatide Once Weekly for the Treatment of Obesity (SURMOUNT-1). New England Journal of Medicine. 2022.
8. Lincoff AM, Brown-Frandsen K, Colhoun HM, et al. Semaglutide and Cardiovascular Outcomes (SELECT). New England Journal of Medicine. 2023.
9. US Food and Drug Administration. Current Good Manufacturing Practice (cGMP) regulations.
10. American Society of Health-System Pharmacists. Drug Shortages Resource Center.
11. Novo Holdings. Catalent acquisition completion announcement, December 2024.
12. US Food and Drug Administration. Counterfeit Ozempic warnings, 2023 and 2024.

Footer disclaimers

Platform Disclaimer. FormBlends is an independent digital health platform. This article provides general supply-chain context and is not a substitute for clinical care, regulatory guidance, or legal advice.

Compounded Medication Notice. Compounded semaglutide and tirzepatide are not FDA-approved. They are prepared by state-licensed compounding pharmacies under individual prescriptions. After the resolution of the GLP-1 shortages, the legal basis for broad compounding of these drugs narrowed substantially. Compounded products are not interchangeable with FDA-approved Ozempic, Wegovy, Mounjaro, or Zepbound.

Results Disclaimer. Supply-chain status describes the availability of FDA-approved medications nationally. Individual pharmacy availability and individual treatment outcomes may vary.

Trademark Notice. Ozempic, Wegovy, Rybelsus, Saxenda, and Victoza are registered trademarks of Novo Nordisk A/S. Mounjaro and Zepbound are registered trademarks of Eli Lilly and Company. Catalent is a registered trademark of Catalent Pharma Solutions. FormBlends is not affiliated with any of these companies.