Insulin Biosimilars: What's Available Now

Insulin

4 FDA-Approved

Four insulin biosimilars have received FDA approval since 2021, with Semglee achieving the first interchangeable designation for any insulin product.

FDA Biosimilar Product Information, 2025

FDA Biosimilar Product Information, 2025

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Half the people in the world who need insulin cannot get it. The World Health Organization estimated in 2021 that roughly 80 million adults with type 2 diabetes required insulin therapy but did not have access, with price being the primary barrier. Insulin biosimilars represent one of the most consequential attempts to close that gap. Since 2021, the FDA has approved four insulin biosimilar products, two of which carry the interchangeable designation that allows pharmacy-level substitution without prescriber involvement. This article maps the full biosimilar insulin landscape: what products exist, how they performed in clinical trials, what they cost, and what the distinction between "biosimilar" and "interchangeable" means in practice. For a broader look at insulin formulations, see rapid-acting vs long-acting insulin analogs. For the story of how insulin became the first peptide therapeutic, see the discovery of insulin.

Why Insulin Is a Biologic, Not a Generic Drug

Insulin is a 51-amino-acid peptide hormone produced by the beta cells of the pancreas. It consists of two chains (A-chain: 21 amino acids; B-chain: 30 amino acids) linked by two disulfide bonds, with an additional intrachain disulfide bond in the A-chain. This three-dimensional structure is critical to function. Even minor folding differences can alter receptor binding, absorption kinetics, and immunogenicity.^[1]

Because insulin is a biologic rather than a small-molecule chemical, it cannot be replicated the way generic aspirin or metformin can. Small-molecule generics are chemically synthesized and can be made identical to the original. Biologics are produced in living cell systems (typically E. coli or yeast for insulin), and the manufacturing process influences the final product's properties. Two manufacturers using different cell lines, fermentation conditions, or purification steps will produce insulin that is highly similar but not identical at the molecular level.

This is why the regulatory pathway for biosimilar insulin differs from the generic drug pathway. In March 2020, insulin products in the United States transitioned from drug regulation (under the Federal Food, Drug, and Cosmetic Act) to biologic regulation (under the Public Health Service Act). This shift meant that new insulin products would be evaluated through the 351(k) biosimilar pathway rather than the 505(b)(2) pathway used for follow-on biologics like Basaglar (insulin glargine) and Admelog (insulin lispro), which were approved before the transition.

The C-peptide, a 31-amino-acid fragment cleaved from proinsulin during insulin biosynthesis, serves as a biomarker for endogenous insulin production and is increasingly recognized for its own biological activity.^[2] Understanding insulin's peptide biology matters for biosimilar development because the manufacturing process must produce not just the correct amino acid sequence but the correct folding, aggregation profile, and post-translational modifications.

FDA-Approved Insulin Biosimilars: The Complete List

Four insulin biosimilars have received FDA approval through the 351(k) pathway. Two are biosimilar to Lantus (insulin glargine), a long-acting basal insulin. Two are biosimilar to NovoLog (insulin aspart), a rapid-acting mealtime insulin.

Semglee: The First Interchangeable Insulin Biosimilar

Semglee (manufactured by Biocon/Viatris) was approved as a biosimilar to Lantus in June 2020 and upgraded to interchangeable status in July 2021. The INSTRIDE clinical program provided the evidence. INSTRIDE 1 enrolled 558 patients with type 1 diabetes and demonstrated equivalent HbA1c reduction at 52 weeks. INSTRIDE 2 enrolled 560 patients with type 2 diabetes and showed noninferiority at 24 weeks. INSTRIDE 3 was the switching study: patients with type 1 diabetes were alternated between Semglee and Lantus multiple times over 36 weeks with no clinically meaningful differences in glycemic control, hypoglycemia, or anti-insulin antibody formation (Engel et al., Diabetes Technology & Therapeutics, 2023).

The interchangeable designation means pharmacists in most US states can substitute Semglee for Lantus without contacting the prescriber, similar to how generic drugs are substituted for brand-name medications. This is a regulatory distinction unique to the United States; most other countries treat all approved biosimilars as substitutable.

Rezvoglar: Biosimilar Without Interchangeability

Rezvoglar (Eli Lilly) was approved in December 2021 as a biosimilar to Lantus but did not pursue interchangeable designation. Its clinical program demonstrated bioequivalence through pharmacokinetic and pharmacodynamic studies plus confirmatory clinical trials showing equivalent glycemic outcomes. Without interchangeable status, a prescriber must specifically write for Rezvoglar rather than relying on pharmacy substitution.

Merilog: The First Rapid-Acting Biosimilar

Merilog (Sanofi) was approved in February 2025 as the first rapid-acting insulin biosimilar, referenced against NovoLog (insulin aspart). Its clinical trials demonstrated comparable pharmacokinetic profiles and equivalent glycemic control in both type 1 and type 2 diabetes. Sanofi announced a patient cost cap of $35 or less for a 30-day supply, available in both prefilled pen and vial formulations.

Kirsty: The First Interchangeable Rapid-Acting Biosimilar

Kirsty (Biocon Biologics) received FDA approval in July 2025 as an interchangeable biosimilar to NovoLog. This made it the first rapid-acting insulin to achieve interchangeable designation, allowing pharmacy-level substitution. The regulatory milestone was significant because it followed the FDA's 2024 guidance eliminating the requirement for dedicated switching studies to demonstrate interchangeability, reducing the cost and timeline for manufacturers seeking this designation.

Biosimilar vs. Interchangeable vs. Follow-On: What the Labels Mean

Three distinct regulatory categories apply to insulin products that are not the original innovator product, and the differences have practical consequences for prescribers, pharmacists, and patients.

Biosimilar (351(k) pathway): The manufacturer demonstrates that the product is "highly similar" to the reference product with no "clinically meaningful differences" in safety, purity, or potency. Clinical trials must confirm comparable efficacy and immunogenicity. Rezvoglar and Merilog hold this designation.

Interchangeable biosimilar (351(k) with interchangeability): The product meets all biosimilar criteria plus additional evidence that it "can be expected to produce the same clinical result as the reference product in any given patient" and that switching between the biosimilar and reference does not increase safety or efficacy risk. Semglee and Kirsty hold this designation. In 2024, the FDA eliminated the requirement for dedicated switching studies, relying instead on the totality of evidence from analytical, nonclinical, and clinical data.

Follow-on biologic (505(b)(2) pathway, pre-2020): Products approved before insulin's 2020 reclassification as a biologic. Basaglar (insulin glargine, Eli Lilly, approved 2015) and Admelog (insulin lispro, Sanofi, approved 2017) were evaluated under the older drug pathway. They demonstrated comparable efficacy but were not held to the same analytical similarity standards as 351(k) biosimilars. Both remain on the market and function similarly to biosimilars in practice.

The practical difference: interchangeable biosimilars can be substituted at the pharmacy counter in most states without prescriber approval, just like generic drugs. Non-interchangeable biosimilars and follow-on biologics require the prescriber to specifically name the product on the prescription.

Clinical Evidence: How Biosimilar Insulins Perform

The clinical evidence for insulin biosimilars spans dozens of trials across multiple products. The most comprehensive synthesis comes from two systematic reviews.

Systematic Review Evidence

Yamada et al. (2022, BMC Endocrine Disorders) conducted a systematic review and meta-analysis of 14 randomized controlled trials encompassing 6,188 patients across different countries, comparing insulin biosimilars to their reference products. The meta-analysis found no clinically meaningful differences in HbA1c reduction, fasting plasma glucose, hypoglycemia incidence, or immunogenicity between biosimilar and reference insulins. These results held across subgroup analyses for type 1 diabetes, type 2 diabetes, and different insulin durations.

An earlier systematic review by Tieu et al. (2018, BMC Endocrine Disorders) examined 11 clinical trials comparing two types of biosimilar insulin glargine with Lantus and one type of biosimilar insulin lispro with Humalog. All pharmacokinetic and pharmacodynamic parameters fell within prespecified equivalence margins. Clinical efficacy and immunogenicity were comparable across all trials. The review noted that extensive experience with marketed insulins indicates that anti-insulin antibodies have minimal or no clinical significance.

Key Individual Trials

SORELLA 1 (insulin lispro biosimilar, SAR342434): This pivotal trial enrolled 507 adults with type 1 diabetes using basal-bolus therapy with insulin glargine. SAR342434 met the primary noninferiority endpoint for HbA1c change from baseline at 26 weeks (least squares mean difference: 0.06%; 95% CI: -0.076 to 0.205). Hypoglycemia rates, adverse events, and anti-insulin antibody profiles were equivalent (Garg et al., Diabetes Technology & Therapeutics, 2017).

SORELLA 2 (SAR342434 in type 2 diabetes): A confirmatory trial in 505 adults with type 2 diabetes using basal-bolus therapy. The results mirrored SORELLA 1: noninferior HbA1c reduction, comparable hypoglycemia, and equivalent safety profiles (Derwahl et al., Diabetes Technology & Therapeutics, 2018).

INSTRIDE 3 (Semglee switching study): Patients with type 1 diabetes were alternated three times between Semglee and Lantus over 36 weeks. No treatment-emergent differences in glycemic control, hypoglycemia rates, or anti-insulin antibody formation were observed after any switch.

The pattern across all trials is consistent: biosimilar insulins perform equivalently to their reference products on every measured clinical endpoint.

Lessons from GLP-1 Peptide Biosimilars

The biosimilar pathway applies broadly to peptide therapeutics. The GLP-1 receptor agonist class provides instructive parallels. Zhang et al. (2023) demonstrated pharmacokinetic similarity between the dulaglutide biosimilar candidate LY05008 and its reference product in a crossover study of healthy subjects.^[3] Liu et al. (2025) followed with a randomized active-comparator trial confirming equivalent efficacy and safety of LY05008 versus Trulicity in Chinese adults with type 2 diabetes.^[4]

Ghosh et al. (2025) showed that a liraglutide biosimilar achieved comparable weight reduction to reference liraglutide in patients with type 2 diabetes and obesity in a post hoc analysis of a phase III trial.^[5] A literature review by Wen et al. (2025) mapped the full GLP-1 biosimilar pipeline, finding that the regulatory framework established by insulin biosimilars is now being applied across the incretin class.^[6]

These GLP-1 biosimilar data matter for insulin because they validate the broader principle: peptide biosimilars, manufactured in living systems and evaluated through the 351(k) pathway, consistently demonstrate clinical equivalence to their reference products. For coverage of how these peptide hormones work together metabolically, see GLP-1 and GIP: the two incretins and why they matter.

Cost and Access: The Economic Impact

The Global Access Gap

Approximately 537 million adults worldwide live with diabetes, and roughly half of those requiring insulin cannot access it reliably. Three companies (Eli Lilly, Novo Nordisk, and Sanofi) control over 90% of the global insulin market. In the United States, the list price of a single vial of Lantus or NovoLog has historically exceeded $300, though actual patient costs vary widely depending on insurance, rebates, and manufacturer discount programs.

Production Costs vs. Market Prices

Gotham et al. (2018, BMJ Global Health) modeled the production costs of biosimilar insulins, estimating that human insulin could be manufactured for under $72 per patient per year and insulin analogs (glargine, lispro, aspart) for under $133 per patient per year. These estimates include raw materials, manufacturing, quality control, and reasonable profit margins but exclude the extensive regulatory costs of bringing a biosimilar to market. The gap between production cost and US market price reflects the complexity of the US pharmaceutical pricing system, including pharmacy benefit manager rebates, formulary positioning negotiations, and the cost of clinical development programs.

Current Biosimilar Pricing

Pricing for approved insulin biosimilars represents a meaningful reduction from originator list prices, though less dramatic than production cost modeling might suggest:

• Semglee: Launched with a list price roughly 65% lower than Lantus. Viatris offers an authorized generic version at $147 per 5-pack of pens.
• Merilog: Sanofi committed to a patient cost cap of $35 or less for a 30-day supply, positioning it as one of the most affordable rapid-acting insulin options.
• CalRx insulin glargine: California's state-sponsored initiative launched in January 2026 at $55 for a five-pack of 3 mL pens, the lowest-cost insulin glargine product in the US market.
• Civica insulin: Blue Cross Blue Shield and Civica Rx announced a biosimilar insulin program targeting $30 per vial beginning in 2026.

Real-World Economic Evidence

Real-world data from international markets confirm that biosimilar introduction reduces insulin prices. A 2025 analysis across 28 European countries found that biosimilar insulin glargine entry reduced reference product prices by 15-40% depending on the market, with the largest reductions in countries with mandatory substitution policies (Atzeni et al., Generics and Biosimilars Initiative Journal, 2025). In Saudi Arabia, switching from Lantus to Basaglar saved between $1.77 million and $23.7 million over four years in a single healthcare system (Al-Agha et al., Diabetes Therapy, 2022).

The economic evidence for insulin glargine formulations, including the second-generation Toujeo (glargine 300 U/mL), shows real-world effectiveness is maintained across formulations.^[7][8]

Safety and Switching: What the Evidence Shows

Immunogenicity

All injectable biologics carry some risk of immunogenicity, meaning the body may produce antibodies against the administered protein. For insulin, anti-insulin antibodies (AIAs) are common with both originator and biosimilar products. The clinically relevant question is whether biosimilar insulins produce different immunogenicity profiles than their reference products.

The answer from clinical trial data is consistently no. The Yamada et al. (2022) meta-analysis found equivalent AIA rates across all biosimilar versus reference comparisons. The Tieu et al. (2018) review reached the same conclusion, noting that anti-insulin antibodies for currently marketed insulin products have "minimal or no clinical significance."

A 2025 FAERS (FDA Adverse Event Reporting System) disproportionality analysis compared post-marketing safety signals between Lantus and Semglee, finding no disproportionate safety signals for the interchangeable biosimilar compared to the originator (Chen et al., Expert Opinion on Drug Safety, 2025).

Switching Between Products

Switching from an originator insulin to a biosimilar is one of the most thoroughly studied questions in the biosimilar literature. The INSTRIDE 3 design, with multiple alternating switches between Semglee and Lantus, was specifically designed to detect any immunogenicity or efficacy signals from repeated switching. None were found.

A broader systematic review of biopharmaceutical switching studies (not limited to insulin) by Cohen et al. (2020) examined 178 studies across multiple therapeutic areas and found no evidence that switching from a reference biologic to its biosimilar increased adverse events, immunogenicity, or reduced efficacy.

The C-peptide, while not directly relevant to biosimilar switching, serves as a useful monitoring tool. Because exogenous insulin (whether originator or biosimilar) suppresses endogenous insulin production, C-peptide levels can help distinguish endogenous from exogenous insulin and track residual beta-cell function during treatment transitions.^[2][9]

What Is Coming Next

The insulin biosimilar pipeline continues to expand. Several rapid-acting and long-acting biosimilar candidates are in late-stage clinical development. The FDA's 2024 decision to eliminate mandatory switching studies for interchangeability designation has lowered the development bar, meaning future biosimilar candidates may reach interchangeable status faster and at lower cost.

Beyond traditional biosimilars, new insulin delivery approaches are in development, including oral insulin formulations, glucose-responsive "smart" insulins, and ultra-concentrated formulations. These represent the next frontier of insulin innovation, building on the peptide biology that makes insulin both a therapeutic cornerstone and a manufacturing challenge. For a deeper look at these emerging technologies, see the future of insulin: smart insulin, oral delivery, and beyond.

The broader lesson from the insulin biosimilar experience applies across peptide therapeutics. The same 351(k) framework that brought Semglee and Kirsty to market is now being applied to GLP-1 receptor agonist biosimilars, with dulaglutide and liraglutide biosimilars already demonstrating clinical equivalence in phase III trials.^[3][4][5] As patents expire on newer peptide therapeutics, the regulatory infrastructure and clinical precedent established by insulin biosimilars will shape how those markets develop. For an overview of GLP-1 drug economics, see cost-effectiveness of GLP-1s.

The Bottom Line

Four insulin biosimilars are FDA-approved, with two carrying interchangeable designations that allow pharmacy-level substitution. Systematic reviews encompassing thousands of patients consistently show no clinically meaningful differences between biosimilar and reference insulins in efficacy, safety, or immunogenicity. Pricing remains a complex picture: biosimilars are cheaper than originators, but the gap between production costs (under $133/year for analogs) and market prices reflects the US pharmaceutical pricing system's structural inefficiencies. The regulatory framework built for insulin biosimilars is now being applied to the GLP-1 agonist class, establishing peptide biosimilars as a durable strategy for improving access to biologic therapies.

Frequently Asked Questions

What is a biosimilar insulin?

A biosimilar insulin is a biologic product that has been shown to be highly similar to an already-approved reference insulin, with no clinically meaningful differences in safety, purity, or potency. Biosimilar insulins are not exact copies of the originator because they are manufactured in living cell systems where the production process influences the final product. The FDA requires extensive analytical, nonclinical, and clinical testing to confirm similarity. Four insulin biosimilars are currently FDA-approved: Semglee, Rezvoglar, Merilog, and Kirsty.

Is biosimilar insulin as effective as brand name insulin?

Clinical trial data from over 6,188 patients across 14 randomized controlled trials shows that biosimilar insulins produce equivalent HbA1c reductions, comparable hypoglycemia rates, and similar immunogenicity profiles to their reference products (Yamada et al., 2022). The INSTRIDE trials for Semglee and SORELLA trials for the lispro biosimilar SAR342434 both demonstrated noninferiority on primary glycemic endpoints. No systematic review has identified clinically meaningful differences between any approved insulin biosimilar and its reference product.

What is the difference between biosimilar and interchangeable insulin?

All interchangeable insulins are biosimilars, but not all biosimilars are interchangeable. A biosimilar demonstrates high similarity to the reference product with no clinically meaningful differences. An interchangeable biosimilar meets an additional standard: evidence that it will produce the same clinical result as the reference product in any given patient and that switching between the two does not increase risk. The practical consequence is that interchangeable biosimilars (Semglee and Kirsty) can be substituted at the pharmacy without prescriber approval, while non-interchangeable biosimilars (Rezvoglar and Merilog) require the prescriber to specify them by name.

How much do biosimilar insulins cost?

Biosimilar insulin prices vary by product and insurance status. Semglee's authorized generic version costs approximately $147 for a five-pack of pens. Sanofi priced Merilog at $35 or less per month for patients. California's CalRx insulin glargine launched in January 2026 at $55 for a five-pack. The Civica Rx/Blue Cross Blue Shield program targets $30 per vial. Production cost modeling suggests insulin analogs could be manufactured for under $133 per patient per year (Gotham et al., 2018), but US market prices remain substantially higher due to the pharmaceutical distribution system's rebate structure.

Can you switch from Lantus to a biosimilar insulin?

Switching from Lantus to Semglee (the interchangeable biosimilar) can happen at the pharmacy level in most US states without a new prescription. The INSTRIDE 3 trial specifically tested multiple alternating switches between Semglee and Lantus in type 1 diabetes patients and found no differences in glycemic control, hypoglycemia, or immunogenicity after any switch. A broader systematic review of 178 biopharmaceutical switching studies found no evidence that switching from reference to biosimilar products increases adverse events or reduces efficacy (Cohen et al., 2020).

Why isn't insulin available as a generic drug?

Insulin transitioned from drug regulation to biologic regulation in the United States in March 2020. As a 51-amino-acid peptide hormone manufactured in living cell systems (E. coli or yeast), insulin cannot be replicated through simple chemical synthesis the way small-molecule generic drugs can. Two manufacturers using different cell lines and purification processes will produce insulin that is highly similar but not molecularly identical. This is why the regulatory pathway requires the more extensive 351(k) biosimilar evaluation rather than the simpler generic drug approval process used for small molecules like metformin or aspirin.