Insulin glargine U100 (Lantus + biosimilars)

Type and role. Insulin glargine U100 is a long-acting basal insulin analog, taken once daily to provide the steady, around-the-clock background insulin a healthy pancreas would supply between meals and overnight.¹ It is not a mealtime insulin and does not cover the rise in glucose after food; people who use it for Type 1 diabetes pair it with a separate rapid-acting insulin at meals.² First approved by the FDA in 2000, it was the drug that made flat, once-daily basal coverage the everyday standard.¹

How it works and its PK/PD. Glargine is engineered to be soluble in its acidic (pH 4) cartridge but to form tiny microprecipitates when injected into the neutral environment under the skin; insulin is then slowly released from that depot.¹ The result is a "relatively constant concentration/time profile over 24 hours with no pronounced peak."¹ Onset is gradual and slower than older NPH insulin, and the FDA label describes an "up to 24-hour duration of action," with the median time to the end of effect around 24 hours (range roughly 11 to over 24 hours).¹ In tightly controlled euglycemic-clamp studies the measured duration was about 19.8 hours after a single dose and about 27 hours at steady state, which is why a minority of people split the dose into twice daily for complete 24-hour cover.³² Compared with the newer ultra-long basals, glargine U100 is slightly less flat and shorter-acting than insulin degludec or the more concentrated glargine U300.⁴

Absorption variability. This is glargine U100's main weakness. In a head-to-head clamp study the day-to-day variability in glucose-lowering effect was about four times higher than degludec's (coefficient of variation roughly 82% versus 20%), and glargine's variability rose sharply more than 8 hours after dosing.⁵ In practice that means somewhat less predictable overnight glucose than the flattest modern basals, though it is far steadier than the NPH insulin it replaced.¹

Behaviour around exercise. As a 24-hour depot, glargine cannot be turned down on the fly: once injected, the basal level is essentially fixed for the day, so activity is managed with carbohydrate and mealtime-insulin adjustments rather than by changing the basal dose.¹

Delivery and approvals. It is given by subcutaneous injection once daily, at the same time each day, from a prefilled pen or vial at the standard U100 (100 units/mL) concentration.¹ It must not be diluted or mixed with other insulins, and must not be given intravenously or through an insulin pump.¹ Glargine has long been approved by the FDA, the EMA, the UK MHRA and other regulators for adults and children with Type 1 diabetes.¹⁶

Access, cost and biosimilars. Glargine U100 is the affordable basal benchmark. Abasaglar (Eli Lilly/Boehringer Ingelheim) became Europe's first biosimilar insulin, approved by the EMA in September 2014, and is marketed as Basaglar in the US.⁶ In July 2021 Viatris/Biocon's Semglee became the first FDA-designated interchangeable biosimilar insulin, meaning a pharmacist can substitute it for Lantus without contacting the prescriber, subject to state law.⁷ Competition and political pressure pushed prices down further: in 2023 Sanofi cut the US list price of Lantus by 78% and capped out-of-pocket cost to a low monthly amount for commercially insured patients, effective January 2024.⁸ Rezvoglar (Eli Lilly) is an additional US glargine product. This breadth of supply is why glargine remains a global reference basal.⁶

What's coming. Glargine U100 is now a mature, off-patent molecule, so the action is in price and access rather than new science: expanding interchangeable-biosimilar competition should keep driving cost down worldwide.⁷⁸ Clinically, it is increasingly positioned as the budget-friendly fallback as flatter, more reproducible basals (degludec, glargine U300) and once-weekly basal insulins under development become the stability frontier — but the most predictable basal you cannot get or afford is not better than the good one you can.⁴⁵

References

1. U.S. Food and Drug Administration / Sanofi. LANTUS (insulin glargine) injection — Highlights of Prescribing Information (Initial U.S. Approval 2000). FDA Drugs@FDA label (2022). https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/021081s076lbl.pdf ↩ ↩² ↩³ ↩⁴ ↩⁵ ↩⁶ ↩⁷ ↩⁸ ↩⁹ ↩¹⁰

2. Home PD, Rosskamp R, Forjanic-Klapproth J, Dressler A. A randomized multicentre trial of insulin glargine compared with NPH insulin in people with type 1 diabetes. Diabetes Metab Res Rev (2005). PubMed PMID 16021649. https://pubmed.ncbi.nlm.nih.gov/16021649/ ↩ ↩²

3. Koehler G, Treiber G, Wutte A, et al. Pharmacodynamics of the long-acting insulin analogues detemir and glargine following single-doses and under steady-state conditions in patients with type 1 diabetes. Diabetes Obes Metab (2014). PubMed PMID 23841569. https://pubmed.ncbi.nlm.nih.gov/23841569/ ↩

4. Goldman J, Kapitza C, Pettus J, Heise T. Understanding how pharmacokinetic and pharmacodynamic differences of basal analog insulins influence clinical practice. Curr Med Res Opin (2017). PubMed PMID 28537449. https://pubmed.ncbi.nlm.nih.gov/28537449/ ↩ ↩²

5. Heise T, Hermanski L, Nosek L, et al. Insulin degludec: four times lower pharmacodynamic variability than insulin glargine under steady-state conditions in type 1 diabetes. Diabetes Obes Metab (2012). PubMed PMID 22594461. https://pubmed.ncbi.nlm.nih.gov/22594461/ ↩ ↩²

6. European Medicines Agency. Abasaglar (insulin glargine) — first biosimilar insulin, EU marketing authorisation (Sept 2014). EMA EPAR (accessed 2026). https://www.ema.europa.eu/en/medicines/human/EPAR/abasaglar-previously-abasria ↩ ↩² ↩³

7. Viatris Inc. and Biocon Biologics. Historic Approval for First Interchangeable Biosimilar Semglee (insulin glargine-yfgn) for the Treatment of Diabetes. Viatris Newsroom (28 July 2021). https://newsroom.viatris.com/2021-07-28-Viatris-Inc-and-Biocon-Biologics-Receive-Historic-Approval-for-First-Interchangeable-Biosimilar-Semglee-R-insulin-glargine-yfgn-injection-for-the-Treatment-of-Diabetes ↩ ↩²

8. Sanofi. Sanofi cuts U.S. list price of Lantus, its most-prescribed insulin, by 78% and caps out-of-pocket Lantus costs at $35 for all patients with commercial insurance. Sanofi Press Release (16 March 2023). https://www.globenewswire.com/en/news-release/2023/03/16/2629188/0/en/Press-Release-Sanofi-cuts-U-S-list-price-of-Lantus-its-most-prescribed-insulin-by-78-and-caps-out-of-pocket-Lantus-costs-at-35-for-all-patients-with-commercial-insurance.html ↩ ↩²