List of Excipients in Branded Drug INSULIN GLARGINE

Insulin Glargine Excipient Strategy and Commercial Opportunities

Last updated: August 6, 2026

Insulin glargine is a mature basal insulin with limited opportunity for new active-ingredient differentiation. Commercial value is concentrated in excipient optimization, high-concentration delivery, device compatibility, stability, preservative control, biosimilar manufacturing, and differentiated storage or administration formats.

The reference product Lantus established the core formulation: insulin glargine in an acidic solution with zinc, m-cresol, glycerol, polysorbate 20, and water for injection. Toujeo uses a higher insulin and zinc concentration to deliver 300 units/mL. Basaglar, Semglee, and Rezvoglar compete through biosimilar development, price, interchangeability, device design, and supply economics rather than novel excipient claims [1-6].

What excipients are used in insulin glargine products?

The principal excipients in marketed insulin glargine products are zinc, m-cresol, glycerol, polysorbate 20, water for injection, and pH-adjusting agents.

Product	Concentration	Key excipient profile	Regulatory position
Lantus, insulin glargine	100 U/mL	Zinc chloride, m-cresol, glycerol, polysorbate 20, water, hydrochloric acid or sodium hydroxide	Reference insulin glargine
Basaglar, insulin glargine	100 U/mL	Zinc, m-cresol, glycerol, polysorbate 20, water, pH adjusters	Biosimilar pathway product
Semglee, insulin glargine-yfgn	100 U/mL	Zinc chloride, m-cresol, glycerol, polysorbate 20, water, pH adjusters	FDA interchangeable biosimilar
Rezvoglar, insulin glargine-aglr	100 U/mL	Zinc, m-cresol, glycerol, polysorbate 20, water, pH adjusters	FDA biosimilar
Toujeo, insulin glargine	300 U/mL	Higher zinc concentration with m-cresol, glycerol, polysorbate 20, water, pH adjusters	High-concentration reference product

Exact excipient quantities vary by product and should be taken from the current FDA prescribing information rather than inferred from the active ingredient or concentration [1-5].

What does each excipient do?

Zinc promotes insulin association and helps control the physical state of insulin glargine in solution and after subcutaneous administration. Zinc concentration is central to the performance distinction between U100 and U300 formulations.

M-cresol is the principal antimicrobial preservative. It also affects protein stability and local tolerability. It is a critical quality attribute because concentration changes can influence aggregation, preservative effectiveness, extractables, and injection-site reactions.

Glycerol adjusts tonicity and contributes to formulation robustness. Its concentration must remain compatible with osmolality targets and subcutaneous tolerability.

Polysorbate 20 reduces interfacial adsorption and can limit agitation-induced aggregation. Its concentration must be controlled because polysorbates can undergo oxidation or hydrolysis, generating degradation products that may affect insulin quality.

Hydrochloric acid and sodium hydroxide adjust the formulation to the acidic pH required for insulin glargine solubility. The formulation is clear and acidic in the vial or pen. After injection into neutral physiological tissue, insulin glargine precipitates and releases insulin gradually.

How does insulin glargine formulation technology create commercial opportunities?

The strongest opportunities are not broad excipient substitution. They are targeted improvements that preserve insulin glargine’s pharmacology while reducing manufacturing, stability, delivery, or patient-use friction.

Opportunity 1: High-concentration formulations

Toujeo demonstrates the commercial value of U300 insulin glargine. A higher concentration reduces injection volume and supports prolonged absorption from the subcutaneous depot. This creates a product position for patients requiring high basal doses.

Commercial opportunities include:

• U300 or other concentrated insulin glargine products for high-dose patients.
• Pen devices that reduce injection burden.
• Formulations optimized for lower injection force.
• Packaging designed for accurate delivery of small injection volumes.
• Combination products using concentrated basal insulin and digital dose management.

The main barrier is clinical and regulatory comparability. Concentration changes can alter absorption, dose conversion, pharmacokinetics, injection-site exposure, and dosing-error risk. A company cannot rely on excipient sameness alone to establish equivalence for a new concentration.

Opportunity 2: Preservative optimization

M-cresol is effective but creates formulation and tolerability constraints. Potential development areas include:

• Lower preservative exposure through improved container closure and multidose-device design.
• Alternative preservatives compatible with insulin stability.
• Preservative-free single-use formats.
• Reduced extractables and leachables from pen cartridges.
• Improved compatibility with infusion or administration systems where applicable.

The regulatory burden is high. Any change to preservative identity or concentration requires evidence on antimicrobial effectiveness, protein aggregation, potency, impurities, sterility assurance, and local tolerability. For a biosimilar, a different excipient system may be possible, but it increases analytical and clinical comparability complexity.

Opportunity 3: Surfactant and interface control

Polysorbate 20 protects against surface adsorption and agitation-related instability. It is also a source of degradation risk. Commercially relevant alternatives include:

• Polysorbate 80 or other surfactants.
• Nonionic surfactants with lower peroxide generation.
• Amino-acid or polymeric stabilizers.
• Low-shear filling and device assembly processes that reduce surfactant dependence.
• Container and cartridge surfaces engineered to reduce insulin adsorption.

A replacement surfactant must be evaluated against insulin aggregation, subvisible particles, potency, oxidation, hydrolysis, syringe or pen compatibility, and long-term storage. The practical opportunity is often process-excipient co-optimization rather than a simple one-for-one substitution.

Opportunity 4: Improved thermal stability

Insulin products face temperature excursions during distribution, home storage, and patient use. Excipient strategies may seek to extend in-use stability or reduce cold-chain exposure.

Potential approaches include:

• Stabilizer systems that limit aggregation during temperature excursions.
• Optimized zinc and surfactant ratios.
• Improved container closure systems.
• Lyophilized or otherwise reformulated presentations.
• Packaging with temperature indicators or insulated delivery systems.

A true room-temperature or extended-temperature insulin glargine product could address access and adherence problems, but it would require robust evidence across potency, impurities, aggregation, sterility, device performance, and in-use conditions. Packaging improvements may reach the market faster than a chemically distinct formulation.

What formulations are protected by insulin glargine patents?

The original insulin glargine composition and manufacturing patent estate is mature. Sanofi’s core U.S. insulin glargine patent, U.S. Patent No. 5,656,722, was granted in 1997 and had a term extending into the mid-2010s, subject to applicable patent-term rules [7].

The commercial patent position is now fragmented across:

• Active-ingredient and protein sequence patents.
• Formulation patents covering concentration, pH, zinc, preservatives, or stabilizers.
• Pen and cartridge patents.
• Manufacturing and purification patents.
• Method-of-use patents covering basal insulin treatment.
• Combination-product and dosing patents.
• Jurisdiction-specific secondary patents.

No single expiration date determines generic or biosimilar entry. Product-specific device patents, formulation claims, pediatric exclusivity, settlement agreements, regulatory exclusivity, and litigation outcomes can affect market access after core composition patents expire.

How strong is the insulin glargine patent estate?

The core molecule provides limited blocking strength because insulin glargine is an established product with multiple approved biosimilar competitors. The stronger remaining barriers are generally operational and product-specific:

Patent or IP layer	Commercial strength
Core insulin glargine composition	Low to moderate for new entrants because of maturity
U100 formulation	Moderate where claims remain enforceable, but design-around potential exists
U300 formulation	Stronger because concentration, dosing, and clinical comparability create added complexity
Pen and cartridge systems	Moderate to strong depending on claim breadth and device adoption
Manufacturing process	Moderate, particularly where process controls affect purity and yield
Method of use	Variable and often vulnerable to label carve-outs
Trade secrets and know-how	High practical value in yield, aggregation control, filling, and device integration

Excipient patents are most defensible when they claim a defined combination linked to a measurable technical effect, such as improved stability, lower aggregation, reduced injection-site reactions, or enhanced delivery performance. Broad claims covering common excipients such as glycerol or m-cresol are less likely to provide durable exclusivity without a narrow concentration range or demonstrated technical result.

What is the FDA regulatory status of insulin glargine biosimilars?

Insulin glargine products are regulated as biologics under the Public Health Service Act. FDA transitioned insulin products, including Lantus, from the drug framework to the biologics framework in 2020 [8].

Product	Sponsor	FDA pathway	Interchangeability
Lantus	Sanofi	Reference product	Not applicable
Basaglar	Eli Lilly and Boehringer Ingelheim	351(k) biosimilar	Not designated interchangeable
Semglee	Viatris and Biocon	351(k) biosimilar	Designated interchangeable
Rezvoglar	Eli Lilly	351(k) biosimilar	Approved as biosimilar; interchangeability status must be checked against current FDA listings

Semglee’s interchangeable designation is commercially important because pharmacy-level substitution depends on state law and payer practice, but interchangeable status can reduce administrative friction relative to a non-interchangeable biosimilar [3,8].

What is the Orange Book status of insulin glargine?

The Purple Book is the primary FDA reference for insulin glargine biologics and biosimilars. The Orange Book is not the principal exclusivity database for products approved under the biologics framework after the transition. Patent and regulatory analysis should therefore combine:

• FDA Purple Book entries.
• FDA prescribing information.
• FDA patent and exclusivity records where applicable.
• USPTO patent records.
• Federal court dockets.
• State substitution rules for interchangeable biologics.

When does insulin glargine lose exclusivity?

Insulin glargine’s core composition exclusivity has already expired in the United States. Biosimilar entry began with Basaglar in 2015, followed by Semglee and Rezvoglar [2-5].

The remaining commercial exclusivity question is product-specific. Lantus, Toujeo, Basaglar, Semglee, and Rezvoglar have different combinations of:

• Regulatory approval dates.
• Device patents.
• Formulation claims.
• Labeling protections.
• Manufacturing know-how.
• Reimbursement contracts.
• Interchangeability status.

The absence of a core molecule patent does not eliminate launch risk. A competitor can face patent litigation over a pen, cartridge, formulation range, manufacturing process, or method of use.

Which companies are challenging the insulin glargine market?

The principal commercial competitors include Sanofi, Eli Lilly, Boehringer Ingelheim, Viatris, and Biocon.

Company group	Product position	Primary competitive lever
Sanofi	Lantus and Toujeo	Brand scale, high-concentration product, payer contracts
Eli Lilly and Boehringer Ingelheim	Basaglar	Established biosimilar volume and price competition
Viatris and Biocon	Semglee	Interchangeability and lower-cost positioning
Eli Lilly	Rezvoglar	Additional biosimilar competition and portfolio scale

The largest opportunity for a new entrant is unlikely to be another undifferentiated U100 vial. A viable product needs at least one of the following:

• Lower cost of goods.
• Interchangeable designation.
• Better pen economics.
• High-concentration dosing.
• Better thermal stability.
• Lower injection burden.
• Improved payer access.
• A differentiated patient population or delivery setting.

What generic and biosimilar launch risks exist for insulin glargine?

Insulin glargine is a biologic, so the relevant pathway is biosimilar development rather than a traditional small-molecule generic application.

Key launch risks include:

1. Analytical comparability. Small differences in aggregation, impurities, glycosylation-related attributes, or potency can delay development.
2. Excipient differences. A distinct excipient system may require more clinical and immunogenicity justification.
3. Device comparability. Pen dose accuracy, injection force, cartridge compatibility, and user handling can become regulatory bottlenecks.
4. Interchangeability. A biosimilar without interchangeability may face slower pharmacy substitution.
5. Manufacturing yield. Insulin economics depend heavily on fermentation, purification, refolding, crystallization, filling, and batch release.
6. Supply reliability. Insulin shortages or manufacturing interruptions can damage payer and prescriber confidence.
7. Price erosion. Multiple biosimilars can compress net pricing before a new entrant achieves scale.
8. Patent litigation. Device and formulation claims may generate Paragraph IV-style disputes in legacy records, but current biologic challenges generally proceed through the Biologics Price Competition and Innovation Act framework rather than a conventional ANDA Paragraph IV filing.

How can excipient suppliers commercialize around insulin glargine?

Excipient companies have four practical routes to revenue.

Formulation development partnerships

Suppliers can provide screening libraries for surfactants, stabilizers, amino acids, polymers, and container-compatible systems. The value proposition must be tied to a specific outcome such as lower aggregation, longer in-use stability, or reduced particle formation.

Device and container compatibility

Insulin glargine is sold primarily in multidose pens and cartridges. Suppliers can develop low-binding materials, silicone alternatives, elastomer systems, and coatings that reduce adsorption or leachables.

Manufacturing process optimization

Excipient suppliers can support cell-culture, purification, refolding, crystallization, and fill-finish operations. Process additives that improve recovery or reduce aggregation may produce greater economic value than a new formulation excipient.

Specialty presentations

Potential products include concentrated insulin glargine, single-use formats, prefilled emergency devices, temperature-tolerant presentations, and combination delivery systems. Each has a different regulatory and patent strategy.

How does insulin glargine compare with competing basal insulins?

Product class	Excipient and formulation opportunity	Commercial position
Insulin glargine U100	Mature zinc, preservative, glycerol, surfactant system	High competition and price pressure
Insulin glargine U300	Concentration and delivery differentiation	Stronger product-level differentiation
Insulin degludec	Distinct multihexamer mechanism and formulation	Competes on duration and dosing flexibility
Insulin detemir	Albumin-binding fatty-acid modification	Reduced commercial importance in some markets
NPH insulin	Protamine-based suspension	Lower-cost alternative with different variability and hypoglycemia profile

Insulin glargine’s best commercial defense is a differentiated presentation supported by device usability, concentration, stability, or payer economics. Excipient novelty alone is unlikely to sustain premium pricing.

Key Takeaways

• Insulin glargine is a mature biologic with expired core molecule exclusivity in the United States.
• The standard formulation uses zinc, m-cresol, glycerol, polysorbate 20, water, and pH adjusters.
• U300 concentration and delivery-system design provide stronger differentiation than routine excipient substitution.
• Preservative reduction, surfactant stability, thermal tolerance, and container compatibility are the most credible excipient development areas.
• Semglee’s interchangeable status gives it a commercial advantage in pharmacy substitution, subject to state law and payer policy.
• Patent risk has shifted from the molecule to formulations, devices, manufacturing processes, and methods of use.
• A new entrant needs a clear cost, access, device, stability, or dosing advantage to compete against Lantus, Toujeo, Basaglar, Semglee, and Rezvoglar.

FAQs

Can insulin glargine be reformulated without m-cresol?

Yes, but a reformulation would require new evidence on antimicrobial protection, insulin stability, aggregation, impurities, sterility, local tolerability, and in-use performance.

Is insulin glargine a small-molecule generic opportunity?

No. FDA regulates insulin glargine as a biologic, and follow-on products generally use the 351(k) biosimilar pathway.

Does Toujeo have stronger patent protection than Lantus?

Toujeo has more product-specific differentiation because of its U300 concentration and associated device and formulation requirements. The applicable patent position must be assessed by jurisdiction and claim family.

Are zinc and m-cresol interchangeable across insulin glargine products?

No. Even where products use the same excipient classes, concentration, grade, source, impurity profile, and interaction with the insulin molecule can differ.

What is the most attractive excipient opportunity in insulin glargine?

The highest-value opportunities are likely to involve aggregation control, extended temperature stability, low-binding container systems, and formulations compatible with concentrated or lower-volume delivery.

References

1. U.S. Food and Drug Administration. (2024). Lantus insulin glargine prescribing information.
2. U.S. Food and Drug Administration. (2024). Basaglar insulin glargine prescribing information.
3. U.S. Food and Drug Administration. (2024). Semglee insulin glargine-yfgn prescribing information.
4. U.S. Food and Drug Administration. (2024). Rezvoglar insulin glargine-aglr prescribing information.
5. U.S. Food and Drug Administration. (2024). Toujeo insulin glargine prescribing information.
6. European Medicines Agency. (2024). Insulin glargine product information.
7. U.S. Patent No. 5,656,722. (1997). Insulin derivatives. United States Patent and Trademark Office.
8. U.S. Food and Drug Administration. (2020). Transition of insulin products and other biological products from the Federal Food, Drug, and Cosmetic Act to the Public Health Service Act.