List of Excipients in Branded Drug REZVOGLAR

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Rezvoglar Excipient Strategy and Commercial Opportunities in Insulin Glargine

Last updated: August 16, 2026

Rezvoglar (insulin glargine-aglr) is Eli Lilly and Boehringer Ingelheim’s U.S. interchangeable biosimilar to Lantus (insulin glargine). Its formulation uses a conventional insulin-glargine excipient system: zinc, m-cresol, glycerol, water, and pH-adjusting agents. The commercial opportunity is concentrated in cost-efficient, tightly controlled supply of pharmaceutical-grade excipients, device-compatible presentations, manufacturing know-how, and differentiated delivery systems rather than in standalone excipient patent protection.

Rezvoglar received FDA approval in December 2021 and interchangeable biosimilar status in July 2023. It is supplied as a 100 units/mL solution in a prefilled KwikPen and is indicated for once-daily subcutaneous treatment of diabetes mellitus in adults and pediatric patients with type 1 diabetes and adults with type 2 diabetes.[1,2]

What excipients are used in Rezvoglar?

Rezvoglar contains insulin glargine at 100 units/mL with zinc, m-cresol, glycerol, water for injection, hydrochloric acid, and sodium hydroxide. The formulation is acidic, with a target pH of approximately 4.0.[1]

Component	Function in Rezvoglar	Commercial relevance
Zinc	Stabilizes insulin hexamers and supports controlled precipitation after injection	Requires low-metal-contaminant, pharmaceutical-grade supply
m-Cresol	Antimicrobial preservative and formulation stabilizer	High-value specialty excipient with compatibility and extractables requirements
Glycerol	Tonicity agent and formulation stabilizer	Commodity-to-specialty opportunity depending on grade and documentation
Hydrochloric acid	pH adjustment	Generally low-cost, but quality and process consistency matter
Sodium hydroxide	pH adjustment	Used for final pH control and batch reproducibility
Water for injection	Vehicle	Critical utility and aseptic manufacturing input

The formulation is designed to keep insulin glargine soluble in the vial or pen at acidic pH. After subcutaneous injection, the solution is neutralized in the tissue, producing microprecipitates from which insulin glargine is released gradually.[1]

Why is m-cresol important in Rezvoglar?

M-Cresol has two roles: it provides antimicrobial protection in the multidose presentation and contributes to insulin formulation stability. Its concentration must be controlled because excessive preservative can affect tolerability, while insufficient concentration can compromise microbial protection.

For suppliers, the key requirements are consistent purity, controlled residual impurities, validated microbial quality, low extractables and leachables risk, and reliable global regulatory documentation. A supplier with an established Drug Master File, strong change-control system, and insulin-product references is more commercially valuable than a low-cost commodity supplier.

What is the role of zinc in insulin glargine?

Zinc promotes formation of insulin hexamers and contributes to the precipitation-and-redissolution mechanism that supports the prolonged action of insulin glargine. Zinc concentration, ionic environment, and mixing conditions can affect particle formation, release behavior, and product consistency.

Zinc is therefore a process-sensitive excipient. The commercial opportunity is strongest for suppliers that can provide tightly specified zinc salts or zinc-containing inputs, impurity control, trace-metal analytics, and supply continuity at biologics manufacturing scale.

How does the Rezvoglar formulation compare with Lantus?

Rezvoglar is highly similar to Lantus in active ingredient, concentration, route of administration, dosage form, and clinical performance. Both products use insulin glargine U-100 in an acidic aqueous formulation with zinc, m-cresol, and glycerol.[1,3]

Attribute	Rezvoglar	Lantus
Active ingredient	Insulin glargine-aglr	Insulin glargine
Strength	100 units/mL	100 units/mL
Formulation type	Acidic aqueous solution	Acidic aqueous solution
Preservative	m-Cresol	m-Cresol
Stabilizing or tonicity components	Zinc and glycerol	Zinc and glycerol
Administration	Subcutaneous injection	Subcutaneous injection
FDA status	Interchangeable biosimilar	Reference product
Primary delivery format	KwikPen prefilled pen	SoloStar pen, vial and other presentations
Clinical duration	Approximately 24 hours or longer, depending on patient response	Approximately 24 hours or longer, depending on patient response

The practical formulation strategy is therefore one of biosimilar replication and manufacturing control, not radical excipient redesign. An excipient change that materially affects insulin aggregation, precipitation, release, immunogenicity, or device performance could create comparability and regulatory problems.

What formulation patents protect Rezvoglar and insulin glargine?

Rezvoglar’s principal regulatory protection comes from the biologics approval pathway and biosimilar requirements rather than from a broad, publicly dominant excipient patent estate.

Lantus-related patent disputes historically centered on insulin glargine formulations, manufacturing methods, delivery devices, and follow-on products. Sanofi and Lilly settled U.S. litigation concerning Basaglar, allowing a commercial launch in December 2016.[4] Core Lantus composition and formulation patents have largely expired or reached the end of their commercial relevance in the United States, which enabled multiple insulin-glargine competitors.

Unlike small-molecule products, biologics are not generally evaluated through the same Orange Book patent-listing framework. FDA’s Purple Book identifies licensed biological products, reference products, biosimilars, and interchangeable biosimilars, but it does not provide an Orange Book-style list of all formulation and device patents.[5]

Does Rezvoglar have Orange Book patents?

Rezvoglar is a biologic, so its market-access analysis should rely on the Purple Book, FDA approval materials, patent databases, device patents, and litigation records rather than assuming a conventional Orange Book patent estate.

A biosimilar applicant can face patent risk involving:

• Manufacturing processes
• Cell-line and expression systems
• Formulation composition
• Pen and cartridge systems
• Container-closure systems
• Use or dosing methods
• Manufacturing analytics and quality-control methods

Many of these rights may be difficult to identify from the product label alone. For commercial diligence, the relevant question is whether a patent can block manufacture, supply, device use, or a specific indication in the target jurisdiction.

When did Rezvoglar obtain FDA approval and interchangeable status?

Milestone	Date	Commercial significance
FDA approval of Rezvoglar	December 2021	Authorized U.S. biosimilar entry
FDA interchangeable designation	July 2023	Permits pharmacy-level substitution under applicable state law and payer policy
U.S. commercial period	From 2022	Expanded insulin-glargine price competition
Reference-product exclusivity context	Lantus reference-product protections substantially elapsed before Rezvoglar approval	Reduced barriers to additional insulin-glargine competitors

Interchangeability does not guarantee automatic substitution in every state. State pharmacy laws, payer formularies, contracting terms, prescriber preferences, and inventory policies determine the practical level of substitution.[2,5]

Which companies compete with Rezvoglar?

Rezvoglar competes with the reference product Lantus and other insulin-glargine products, including Basaglar and Semglee. It also competes indirectly with other basal insulins such as Toujeo, Tresiba, and biosimilar or follow-on insulin products.

Product	Company	Active ingredient	U.S. competitive position
Lantus	Sanofi	Insulin glargine	Reference product
Basaglar	Lilly and Boehringer Ingelheim	Insulin glargine	Follow-on insulin-glargine product
Rezvoglar	Lilly and Boehringer Ingelheim	Insulin glargine-aglr	Interchangeable biosimilar
Semglee	Viatris and Biocon	Insulin glargine-yfgn	Interchangeable biosimilar
Toujeo	Sanofi	Insulin glargine U-300	Higher-concentration basal insulin
Tresiba	Novo Nordisk	Insulin degludec	Competing long-acting basal insulin

Semglee’s interchangeable status and Rezvoglar’s interchangeable designation increase formulary and payer leverage against Lantus. The primary differentiators are net price, rebate structure, distribution, pen availability, patient support, contracting, and pharmacy substitution.

What commercial opportunities exist for Rezvoglar excipients?

Pharmaceutical-grade m-cresol supply

M-Cresol is the clearest specialized excipient opportunity. Suppliers can compete through:

• Insulin-grade purity
• Validated microbial control
• Low trace-metal content
• Consistent preservative assay
• Stable global supply
• Regulatory support for post-approval changes
• Packaging that limits contamination and evaporation

Because m-cresol is present in several insulin formulations, a supplier that qualifies with one manufacturer can pursue broader basal and rapid-acting insulin portfolios.

Zinc and metal-control systems

Zinc-related opportunities include higher-purity zinc inputs, analytical testing, and process-control services. Manufacturers may value suppliers that provide lot-to-lot control over metal impurities and support investigations involving insulin aggregation, precipitation, or release variability.

Glycerol and formulation-grade polyols

Glycerol is more widely available than m-cresol, but pharmaceutical-grade glycerol with reliable global documentation can support cost reduction and supply resilience. Suppliers can differentiate through low endotoxin levels, compendial compliance, validated bioburden controls, and dual-region manufacturing.

Container-closure and device compatibility

Rezvoglar is delivered through a prefilled pen. The commercial opportunity extends beyond excipients to:

• Cartridge glass and coatings
• Elastomeric components
• Needle interfaces
• Silicone-oil control
• Extractables and leachables testing
• Pen dosing accuracy
• Cold-chain packaging
• Human-factors engineering

Device components can create practical barriers even when the formulation itself is well established. A supplier that supports both excipient qualification and device compatibility has a stronger position than a single-input supplier.

What manufacturing and intellectual-property barriers affect Rezvoglar?

Insulin glargine is a recombinant protein, so manufacturing barriers include expression yield, protein folding, purification, aggregation control, zinc incorporation, aseptic filling, and consistent precipitation behavior after injection.

The most defensible assets may be manufacturing know-how and process controls rather than composition patents. Important technical capabilities include:

1. High-yield recombinant production.
2. Removal of process-related impurities and host-cell proteins.
3. Control of insulin-related substances and aggregates.
4. Consistent zinc and preservative content.
5. Stable filling into cartridges and pens.
6. Demonstrated similarity across analytical, functional, pharmacokinetic, and immunogenicity testing.

A competitor can avoid an expired composition claim yet still face operational difficulty reproducing product quality at commercial scale.

What generic entry risks exist for Rezvoglar?

Rezvoglar does not face conventional generic substitution risk in the same way as an ordinary small molecule. Its principal risks are additional biosimilar entry, price erosion, payer exclusion, and substitution competition from interchangeable products.

Biosimilar and follow-on risk

Semglee already establishes interchangeable insulin-glargine competition. Additional entrants could target the same U-100 basal-insulin segment through lower pricing or regional supply agreements.

Formulation risk

A formulation change involving m-cresol, zinc, glycerol, pH, or container materials could require extensive comparability work. Any change that affects insulin aggregation, release, stability, or immunogenicity can delay approval or increase post-approval obligations.

Commercial substitution risk

Interchangeability increases the probability of substitution, but commercial uptake depends on state law and payer policy. A product with weaker contracting or limited pen supply can lose share despite having interchangeable status.

How strong is the Rezvoglar patent estate?

Rezvoglar’s defensibility is moderate at the product level and stronger at the manufacturing and device level.

Asset category	Relative protection
Basic insulin-glargine composition	Limited because the molecule and core formulation are mature
Excipients alone	Limited; zinc, m-cresol, glycerol, and pH agents are established inputs
Specific formulation ranges	Potentially relevant but vulnerable to prior-art and obviousness challenges
Manufacturing process	Stronger if process-specific and difficult to design around
Pen and cartridge system	Potentially strong where claims cover device architecture or use
Quality-control methods	Commercially valuable, often protected as know-how
Interchangeable regulatory status	Valuable for substitution but not an exclusive patent right

Paragraph IV challenges are generally associated with abbreviated new drug applications for small molecules. For Rezvoglar and other biologics, the relevant pathway is the Biologics Price Competition and Innovation Act, including the patent-exchange and litigation framework for biosimilars.[5,6]

What is the revenue exposure for insulin glargine competition?

Sanofi has historically reported Lantus as a major diabetes product, but product sales are affected by price concessions, biosimilar competition, and shifts to Toujeo and other basal insulins. Lilly and Boehringer do not always disclose Rezvoglar revenue separately from broader diabetes or insulin portfolios.

The commercial exposure is therefore best measured through:

• U.S. insulin-glargine prescription volume
• Net price after rebates
• Formulary placement
• Interchangeable substitution rates
• Pen versus vial mix
• Medicaid and Medicare utilization
• Hospital and health-system contracts
• Manufacturing cost per pen

The largest excipient opportunity is linked to sustained multi-product insulin demand rather than Rezvoglar alone. A supplier that supports Lantus competitors, rapid-acting insulins, and biosimilar insulin programs can reduce dependence on a single brand.

Key Takeaways

• Rezvoglar uses a conventional insulin-glargine formulation containing zinc, m-cresol, glycerol, water, hydrochloric acid, and sodium hydroxide.
• M-Cresol is the highest-value specialized excipient opportunity because it combines preservative, stability, quality, and regulatory requirements.
• Zinc control is technically important because it affects insulin hexamer formation and post-injection precipitation.
• The product received FDA approval in December 2021 and interchangeable biosimilar status in July 2023.
• Rezvoglar competes directly with Lantus, Basaglar, and Semglee, and indirectly with Toujeo and Tresiba.
• Product-level excipient patent protection is limited; manufacturing, device, process-control, and supply-chain capabilities provide stronger competitive barriers.
• Commercial opportunities include excipient supply, analytical services, container-closure systems, pen components, cold-chain packaging, and insulin manufacturing technology.
• Biosimilar entry, payer contracting, pharmacy substitution, and price erosion are the main generic-entry risks.
• Rezvoglar revenue is not generally disclosed as a standalone figure, so market exposure should be evaluated through insulin-glargine volume, net pricing, and formulary access.

FAQs About Rezvoglar Excipient Strategy

Is Rezvoglar preservative-free?

No. Rezvoglar contains m-cresol, which supports antimicrobial protection in the multidose pen presentation.[1]

Can m-cresol be replaced in an insulin-glargine biosimilar?

Replacement is technically possible, but it would require extensive formulation development and comparability work. The replacement must preserve sterility assurance, stability, tolerability, device compatibility, and clinical performance.

Does Rezvoglar contain polysorbate 20?

The U.S. prescribing information identifies zinc, m-cresol, glycerol, water, hydrochloric acid, and sodium hydroxide as formulation components. It does not identify polysorbate 20 as an excipient.[1]

Is Rezvoglar interchangeable with all insulin products?

No. Rezvoglar is interchangeable with its reference product, Lantus, subject to applicable FDA and state pharmacy requirements. Interchangeability does not extend to Toujeo, Tresiba, or unrelated insulin products.

Are insulin-glargine excipients suitable targets for excipient licensing deals?

Yes, particularly where the deal combines high-purity m-cresol or zinc supply with regulatory files, analytical methods, manufacturing support, and device compatibility data. Pure commodity supply has weaker licensing value than a qualified, multi-region, change-controlled platform.

References

1. U.S. Food and Drug Administration. (2023). Rezvoglar (insulin glargine-aglr) prescribing information. FDA.

2. U.S. Food and Drug Administration. (2023, July 28). FDA approves first interchangeable biosimilar insulin product. FDA.

3. U.S. Food and Drug Administration. (2022). Lantus (insulin glargine injection) prescribing information. FDA.

4. Eli Lilly and Company. (2015). Lilly and Boehringer Ingelheim announce settlement agreement with Sanofi regarding Basaglar. Company release.

5. U.S. Food and Drug Administration. (2024). Purple Book: Database of licensed biological products. FDA.

6. U.S. Congress. (2010). Biologics Price Competition and Innovation Act of 2009, Pub. L. No. 111-148, §§ 7001-7003.