Insulin Glargine (Lantus, Toujeo)

Insulin glargine was the first long-acting "basal" insulin analog, approved in 2000 on a genuinely different piece of chemistry than the rapid-acting analogs on this site: instead of speeding absorption up, it's engineered to precipitate under the skin and release slowly over about 24 hours. It's also the insulin at the center of this site's most consequential patent-litigation story — a multi-patent lawsuit against Eli Lilly that delayed a rival product by more than a year, and a separate suit against Merck that ended with a competing product withdrawn entirely, years before either insulin lispro or insulin aspart faced comparable competition.

The first long-acting basal insulin analog

Where insulin lispro and insulin aspart are engineered to act faster than regular human insulin for mealtime dosing, insulin glargine solves the opposite problem: providing steady, background ("basal") insulin coverage across a full day with a single injection. The FDA approved Sanofi's Lantus (insulin glargine injection) on 20 April 2000 (NDA 021081) — the first long-acting insulin analog ever approved, intended to replace multiple daily injections of older intermediate-acting insulins like NPH, which peak unpredictably and require more careful meal timing around that peak.

A precipitate depot instead of a faster hexamer breakup

Insulin glargine reaches its long, flat action profile through a structural change unrelated to the rapid-acting analogs' hexamer-breakup trick: two arginine molecules are added to the end of the insulin B-chain, and the amino acid at position A21 is changed from asparagine to glycine (to prevent that acid-sensitive site degrading in the drug's acidic formulation). Together, these changes shift the molecule's isoelectric point from human insulin's pH 5.4 up to pH 6.7 — close to the body's own physiological pH. The drug is manufactured as a clear solution at pH 4, in which it's fully soluble, but once injected into subcutaneous tissue, the solution is neutralized toward physiological pH and the insulin precipitates into a solid depot under the skin. From that depot, small amounts of insulin glargine slowly and continuously redissolve into circulation over roughly 24 hours with no pronounced peak — a genuinely different mechanism from a rapid-acting analog dissociating faster into monomers, aimed at the opposite clinical goal.

Toujeo: a more concentrated, flatter-acting reformulation

On 25 February 2015, the FDA approved Toujeo (insulin glargine injection, 300 units/mL) — the same glargine molecule as Lantus, reformulated at three times the concentration (U-300 instead of U-100). Because the same total dose is delivered in a smaller injected volume, the resulting subcutaneous depot has proportionally less surface area relative to its volume, releasing even more slowly and evenly than standard-concentration Lantus. Sanofi's supporting evidence came from the EDITION Phase 3 trial program, a series of international randomized studies enrolling more than 3,500 participants across type 1 and type 2 diabetes, which found Toujeo achieved comparable glycemic control to Lantus with a flatter, more stable day-to-day glucose profile and generally lower rates of nocturnal hypoglycemia.

The patent fight that shaped its biosimilar competition

Lantus's route to competition ran through patent litigation more directly than either lispro's or aspart's. Eli Lilly and Boehringer Ingelheim's Basaglar (their own insulin glargine product) received tentative FDA approval in August 2014, but Sanofi sued, alleging that Basaglar and its KwikPen injector device infringed patents covering Lantus's own SoloStar pen. The companies settled on 28 September 2015: Sanofi granted Lilly a royalty-bearing license to manufacture and sell Basaglar in the KwikPen device, in exchange for royalty payments, with Basaglar cleared to launch in the US no earlier than 15 December 2016 — a full 16 months after the settlement, and more than two years after Basaglar's original tentative approval. Separately, in September 2016 Sanofi sued Merck over a competing insulin glargine product Merck was developing with Samsung Bioepis (Lusduna Nexvue), after Merck's own FDA application disclosed a challenge to ten Sanofi patents covering Lantus — automatically triggering a 30-month regulatory stay on final approval under the Hatch-Waxman Act. The FDA still granted Lusduna Nexvue tentative approval in July 2017 despite that stay, but rather than wait out the litigation, Merck terminated its partnership with Samsung Bioepis in 2018 — paying $155 million toward Samsung's sunk investment in the product — and Lusduna Nexvue was never launched in the US at all. Basaglar reached the market in December 2016; Mylan (later Viatris) and Biocon's Semglee followed a different route again — approved on 11 June 2020 as a copy of Lantus's amino-acid sequence under the same NDA-turned-deemed-biologic framework Basaglar used, then on 28 July 2021 as the first interchangeable insulin biosimilar of any kind, the FDA's stricter designation letting pharmacies substitute it without a prescriber's sign-off, as described on this site's Insulin page.

Current status

Lantus and Toujeo remain actively marketed by Sanofi, competing against Basaglar (Lilly/Boehringer Ingelheim) and the biosimilar Semglee (Viatris/Biocon). As described on this site's Insulin page, Sanofi is also named in the 2025-2026 "most-favored-nation" manufacturer pricing agreements running through the federal TrumpRx platform. Insulin glargine's current market — an originator, a patent-settlement-enabled follow-on, and a true interchangeable biosimilar all competing for the same basal-insulin patients — is a direct, traceable result of the litigation history above, not simply the passage of the underlying patents' expiration dates.