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Insulin Glulisine (Apidra)

Written by The Peptide Record editorialClinical review not yet completedLast reviewed 16 September 2026Funding No ads, no affiliate links, no vendor payment

Insulin glulisine is the third rapid-acting insulin analog approved in the US, arriving in 2004 — eight years after insulin lispro and four after insulin aspart — with a genuinely different piece of engineering: where both earlier analogs still rely on zinc to control their own hexamer breakup, glulisine's two amino-acid substitutions let it ship as the only rapid-acting analog formulated without zinc at all, dissociating into active monomers even faster in head-to-head comparisons. It has never had a pricing scandal or a landmark lawsuit attached to its name the way this site's insulin lispro and insulin glargine pages describe — its most notable recent turn is a plainer one: a 70% US list-price cut Sanofi announced in 2023 and put into effect in January 2024, alongside comparable cuts from every other major insulin manufacturer that same year.

On this page
  1. A third rapid-acting analog, and a zinc-free trick
  2. The pivotal evidence, in both type 1 and type 2 diabetes
  3. Pumps, pediatric use, and a faster onset than aspart
  4. A 70% price cut, not a pricing scandal
  5. Current status

In brief

Should you care? Relevant if you use, or are comparing, rapid-acting mealtime insulin alongside this site's insulin lispro and insulin aspart pages — a third, independently engineered analog with a distinct formulation trick and, so far, no biosimilar competition.

The short version

  • What it is: two amino-acid substitutions (asparagine to lysine at B3, lysine to glutamic acid at B29) that let insulin glulisine skip the zinc every other rapid-acting analog on this site still uses to control hexamer formation — it self-associates weakly enough to be stabilized with a non-ionic surfactant instead.
  • FDA-approved 16 April 2004 (Sanofi-Aventis, as Apidra, NDA 021629), backed by a 672-patient type 1 diabetes trial against insulin lispro and an 876-patient type 2 diabetes trial against regular human insulin, both over 26 weeks.
  • The real recent story is a price cut, not a scandal: Sanofi cut Apidra's US list price 70% effective January 2024 — smaller than Lantus's 78% cut the same year, but part of the same real, verifiable affordability push, not marketing language.

A third rapid-acting analog, and a zinc-free trick

This site's insulin lispro and insulin aspart pages each describe a single amino-acid change near the end of the insulin B-chain that weakens the hormone's tendency to self-associate into slow-absorbing hexamers. Insulin glulisine, developed by Sanofi-Aventis and FDA-approved as Apidra on 16 April 2004 (NDA 021629), takes a different route to the same rapid-acting goal: asparagine at position B3 is replaced with lysine, and lysine at position B29 is replaced with glutamic acid. The B3 substitution introduces steric and electrostatic repulsion against a neighboring arginine that speeds hexamer-to-monomer dissociation, while the B29 change stabilizes the resulting monomer well enough that glulisine is the only one of the three rapid-acting analogs covered on this site formulated entirely without zinc — instead relying on the non-ionic surfactant polysorbate 20 for stability. The changes also shift glulisine's isoelectric point down to about pH 5.1, versus pH 5.5 for unmodified human insulin, further improving its solubility at physiological pH.

The pivotal evidence, in both type 1 and type 2 diabetes

Glulisine's approval rested on two separate 26-week, randomized, open-label, multicenter trials. In type 1 diabetes, 672 adults were randomized to mealtime glulisine or insulin lispro, both alongside basal insulin; the adjusted mean HbA1c change from baseline was statistically indistinguishable between the two drugs (-0.14% in both arms), with comparable rates of hypoglycemia (Dreyer M, Prager R, Robinson A, et al., "Efficacy and Safety of Insulin Glulisine in Patients With Type 1 Diabetes," Horm Metab Res 2005;37(11):702-707, PMID 16308840, DOI: 10.1055/s-2005-870584).1 In type 2 diabetes, a separate 876-patient trial randomized participants to mealtime glulisine or regular human insulin, both with basal NPH insulin; glulisine produced a slightly larger HbA1c reduction (-0.46% vs. -0.30%, P=0.0029) and significantly better postprandial glucose control at one and two hours after meals (Dailey G, Rosenstock J, Moses RG, Ways K, "Insulin Glulisine Provides Improved Glycemic Control in Patients With Type 2 Diabetes," Diabetes Care 2004;27(10):2363-2368, PMID 15451901, DOI: 10.2337/diacare.27.10.2363).2 Neither trial found a meaningful difference in overall hypoglycemia risk between glulisine and its comparator — the case for glulisine was built on matching or modestly beating existing options on glycemic control, not on a dramatically different clinical outcome.

Pumps, pediatric use, and a faster onset than aspart

Apidra's label expanded twice after its original 2004 approval. On 29 October 2008, the FDA approved glulisine for children 4 years and older with type 1 diabetes, based on a 572-patient, 26-week active-controlled trial in 4-to-17-year-olds comparing glulisine to insulin lispro. Separately, Apidra's label permits use in external insulin infusion pumps and, under medical supervision, intravenous administration in acute or hospital settings — uses this site's insulin lispro and insulin aspart pages describe similarly for their own products. A small, randomized crossover trial in twelve healthy volunteers under glucose-clamp conditions found glulisine reached 10% of its maximum glucose-infusion-rate effect faster than insulin aspart (a median 9 minutes vs. 17 minutes, P=0.0146) — a real, if modest, pharmacodynamic difference the trial's own authors attributed specifically to glulisine's zinc-free formulation (Arnolds S, Rave K, Hövelmann U, et al., "Insulin Glulisine Has a Faster Onset of Action Compared with Insulin Aspart in Healthy Volunteers," Exp Clin Endocrinol Diabetes 2010;118(9):662-664, PMID 20429049, DOI: 10.1055/s-0030-1252067).3

A faster lab measurement, not a proven clinical advantage

A faster time-to-onset in healthy volunteers under controlled glucose-clamp conditions is a real pharmacodynamic finding, not the same thing as a meaningfully better real-world outcome for people with diabetes — the larger comparative trials in section 2 above, run in actual patients rather than healthy volunteers, found glulisine roughly matching rather than clearly beating its comparators on the outcomes that matter clinically (HbA1c, hypoglycemia). Treat the onset-speed finding as a genuine mechanistic detail, not as marketing evidence that glulisine works better.

A 70% price cut, not a pricing scandal

Unlike insulin lispro's tenfold price rise and the Alec Smith story described on this site's insulin lispro page, or insulin glargine's multi-year patent litigation described on the insulin glargine page, Apidra's pricing history has no comparably dramatic public episode attached to it. Its most recent notable development is a straightforward affordability move: on 16 March 2023, Sanofi announced it would cut Apidra's US list price by 70% and Lantus's by 78%, effective 1 January 2024, alongside a $35-per-month out-of-pocket cap for eligible patients — moves that followed similar list-price cuts and coverage caps announced by Eli Lilly and Novo Nordisk for their own insulin lines around the same time, part of a broader, real, multi-manufacturer response to years of public and legislative pressure over US insulin costs rather than a single-company story unique to Apidra.

Current status

Apidra remains FDA-approved and actively marketed by Sanofi in vial, cartridge and SoloStar prefilled-pen forms, for both adult and pediatric (4 years and older) use in type 1 diabetes, and adult use in type 2 diabetes. Unlike insulin aspart, which picked up its first FDA-approved biosimilar (Merilog) and first interchangeable biosimilar (Kirsty) in 2025, no biosimilar or interchangeable version of insulin glulisine has been approved in the US as of this review — Apidra's competitive position among rapid-acting analogs currently rests entirely on its original branded formulation and its 2024 price cut, not on lower-cost generic-style competition the way aspart and glargine both now have.

References

  1. FDA approval of Apidra (insulin glulisine [rDNA origin] injection, NDA 021629, Sanofi-Aventis), 16 April 2004.
  2. Dreyer M, Prager R, Robinson A, Busch K, Ellis G, Souhami E, Van Leendert R, "Efficacy and Safety of Insulin Glulisine in Patients With Type 1 Diabetes," Horm Metab Res 2005;37(11):702-707, PMID 16308840, DOI: 10.1055/s-2005-870584 — 672 patients randomized to glulisine or insulin lispro over 26 weeks; adjusted mean HbA1c change -0.14% in both arms.
  3. Dailey G, Rosenstock J, Moses RG, Ways K, "Insulin Glulisine Provides Improved Glycemic Control in Patients With Type 2 Diabetes," Diabetes Care 2004;27(10):2363-2368, PMID 15451901, DOI: 10.2337/diacare.27.10.2363 — 876 patients randomized to glulisine or regular human insulin over 26 weeks; HbA1c change -0.46% vs. -0.30%, P=0.0029.
  4. FDA approval of Apidra for pediatric use (ages 4 and older), 29 October 2008, based on a 572-patient, 26-week active-controlled trial in patients 4-17 years old; Arnolds S, Rave K, Hövelmann U, Fischer A, Sert-Langeron C, Heise T, "Insulin Glulisine Has a Faster Onset of Action Compared with Insulin Aspart in Healthy Volunteers," Exp Clin Endocrinol Diabetes 2010;118(9):662-664, PMID 20429049, DOI: 10.1055/s-0030-1252067.
  5. Sanofi 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," 16 March 2023 (also announcing a 70% Apidra list-price cut, both effective 1 January 2024) — cross-checked against contemporaneous trade coverage (Reuters, Drug Topics, Time); FDA approval of Merilog (insulin aspart-szjj), 14 February 2025, and Kirsty (insulin aspart-xjhz), 15 July 2025, as the first rapid-acting insulin biosimilar and first interchangeable rapid-acting insulin biosimilar respectively — no comparable insulin glulisine biosimilar approved as of this review.