Insulin glulisine
Sanofi's rapid-acting mealtime insulin, interchangeable in trials with lispro and aspart
Insulin glulisine is a rapid-acting insulin analogue, sold as Apidra, with two amino acids changed so it absorbs faster than regular human insulin. It is injected within 15 minutes before a meal or soon after starting one, or used in insulin pumps. In head-to-head trials it controlled blood sugar as well as insulin lispro and aspart. FDA approved it in 2004 for adults and children with diabetes.
What is it?
Human insulin clusters into hexamers under the skin, which slows absorption. Glulisine swaps asparagine for lysine at position B3 and lysine for glutamic acid at B29, which helps it stay as smaller units and reach the blood faster. According to the Apidra label, its half-life after a subcutaneous injection is about 42 minutes, against 86 minutes for regular human insulin, and it can be injected within 15 minutes before a meal or within 20 minutes after starting one.
Its trials mostly asked whether it matched the other rapid analogues, and the answer was yes. In children and adults on basal-bolus therapy, HbA1c changes were similar to insulin lispro, well within the non-inferiority margin. In insulin pumps it had slightly more unexplained high glucose or infusion-set occlusions than aspart or lispro, with no difference in HbA1c or severe hypoglycaemia. Pump users with fat loss at their infusion sites, though, saw that lipoatrophy improve after switching to it in a small study.
Much of its later evidence is in 'basal-plus' regimens: a basal insulin with one mealtime injection. Added once a day to basal insulin in type 2 diabetes, it matched premixed insulin on HbA1c with better treatment satisfaction; in India, a basal-plus regimen lowered HbA1c where premixed insulin did not. In Japan, glargine 300 plus glulisine gave more time in range and fewer lows than twice-daily degludec-aspart, and pairing iGlarLixi with a single glulisine dose matched four daily injections.
Head to head with a GLP-1 agonist on top of glargine, glulisine and lixisenatide lowered HbA1c about equally over 8 weeks, but lixisenatide did more for post-meal glucose and weight. A biosimilar version has now matched the original on immune response and HbA1c over 26 weeks.
The label indicates Apidra to improve glycaemic control in adults and children with diabetes, generally with an intermediate- or long-acting insulin; as with all insulins, hypoglycaemia is the main risk, and doses may need adjusting with changes in activity, meals, illness or kidney and liver function. In hospital it can also be infused intravenously under supervision, diluted to 0.05 to 1 unit/mL in saline.
Mechanism of Action
Insulin glulisine is a rapid-acting analogue with two amino-acid changes that keep it from clustering, so it is absorbed fast at mealtimes.
B3 and B29 substitutions
Lysine at B3 and glutamic acid at B29 reduce self-association into hexamers.
Fast absorption
Half-life about 42 minutes after subcutaneous injection (label 12.3).
Insulin receptor
Once absorbed it lowers post-meal glucose as human insulin does.
Published Research
These are randomised and comparative trials of insulin glulisine, read from their PubMed abstracts.
Glulisine vs lispro in basal-bolus therapy
HbA1c changed by 0.10% on glulisine and 0.16% on lispro, a difference of -0.06% against a non-inferiority margin of 0.4%.
Insulin pumps: glulisine vs aspart vs lispro
Unexplained hyperglycaemia or infusion-set occlusion occurred in 68.4% on glulisine against 62.1% on aspart and 61.3% on lispro, with no differences in HbA1c or severe hypoglycaemia.
Basal plus one glulisine dose vs premixed insulin
Over 24 weeks the basal-plus regimen was non-inferior to biphasic insulin for HbA1c (difference 0.21%), and treatment satisfaction favoured basal plus.
Biosimilar vs original glulisine
At 26 weeks immune responses persisted in 16% and 24% of patients, and HbA1c fell similarly (0.53% vs 0.38%), meeting non-inferiority.
Bolus glulisine against basal glargine
In type 2 diabetes, mealtime glulisine lowered post-lunch, post-dinner and bedtime glucose more than basal glargine, while glargine lowered fasting glucose more; glargine but not glulisine raised parasympathetic tone.
Basal plus glulisine against premixed insulin in India
In insulin-naive Indian adults with type 2 diabetes, glargine plus glulisine lowered HbA1c by 0.7% at 24 weeks while premixed insulin did not change it significantly; 83.2% on the basal-plus regimen needed an extra glulisine dose.
Against degludec-aspart twice daily
In Japanese patients on continuous glucose monitoring, glargine 300 plus glulisine gave more time in range (84.2% against 73.1%) and less hypoglycaemia, including at night, than twice-daily degludec-aspart.
With iGlarLixi instead of four injections
In Japanese adults with type 2 diabetes, iGlarLixi plus one glulisine dose matched multiple daily injections for time in range, with less time in level 1 hypoglycaemia and a shorter titration period.
Lipoatrophy in pump users
In 14 pump users with lipoatrophy, switching to glulisine improved subcutaneous fat thickness and the number and size of atrophic sites over 12 months, compared with controls.
Against lixisenatide on basal glargine
In type 2 diabetes on glargine, once-daily glulisine and lixisenatide lowered HbA1c similarly (0.6% and 0.8%) over 8 weeks; lixisenatide lowered post-meal glucose and weight more and did not change kidney haemodynamics.
Dosing Data
Apidra is injected within 15 minutes before a meal or within 20 minutes after starting one, usually with a longer-acting insulin; doses are individualised.
Educational information, not medical advice. Each dose above is tagged with its source: an approved label, a published human study, animal data, or amounts reported by users. None is a recommendation for you. An unapproved compound has no established safe or effective human dose, and products sold for “research use only” are not made or tested for people. Talk to a doctor before acting on anything on this site, including before you start, stop or change any medicine or dose. Full medical disclaimer.
Side Effects & Contraindications
Reported Side Effects
From the Apidra label and the trials above.
Contraindications & Cautions
From the label; a clinician decides.
Legal Status
Insulin glulisine is an FDA-approved prescription medicine.
Frequently Asked Questions
?What is insulin glulisine?
A rapid-acting mealtime insulin analogue sold as Apidra, used by injection or in insulin pumps by adults and children with diabetes.
?Is it better than lispro or aspart?
Trials found it about equivalent for blood sugar control; in pumps it had slightly more infusion-set problems.
?How fast does it work?
It is absorbed faster than regular insulin, with a subcutaneous half-life of about 42 minutes against 86 for regular insulin, so it is taken close to meals.
?Can it be taken after eating?
Yes. The label allows injection within 15 minutes before a meal or within 20 minutes after starting the meal.
References
- [fda-pi] Sanofi. APIDRA (insulin glulisine injection), US prescribing information: indication, pharmacokinetics (subcutaneous half-life about 42 minutes vs 86 minutes for regular human insulin). DailyMed version effective November 25, 2025; read September 30, 2026.
- [pubmed] Philotheou A, et al. "Comparable efficacy and safety of insulin glulisine and insulin lispro when given as part of a Basal-bolus insulin regimen in a 26-week trial in pediatric patients with type 1 diabetes." Diabetes Technol Ther, 2011;13(3):327-34. PMID: 21291333.
- [pubmed] van Bon AC, et al. "Insulin glulisine compared to insulin aspart and to insulin lispro administered by continuous subcutaneous insulin infusion in patients with type 1 diabetes: a randomized controlled trial." Diabetes Technol Ther, 2011;13(6):607-14. PMID: 21457066.
- [pubmed] Vora J, et al. "Intensifying insulin regimen after basal insulin optimization in adults with type 2 diabetes: a 24-week, randomized, open-label trial comparing insulin glargine plus insulin glulisine with biphasic insulin aspart (LanScape)." Diabetes Obes Metab, 2015;17(12):1133-41. PMID: 26085028.
- [pubmed] Drai R, et al. "Immunogenicity, efficacy and safety of a biosimilar insulin glulisine compared with originator in adults with type 1 diabetes mellitus: A phase III randomised clinical trial." Diabetes Obes Metab, 2026;28(3):1791-1799. PMID: 41366610.
- [fda] FDA. Drugs@FDA (openFDA): APIDRA, BLA 021629, approved April 16, 2004. Read September 30, 2026.
- [clinical-trial] Takeshita Y, et al. "Metabolic and sympathovagal effects of bolus insulin glulisine versus basal insulin glargine therapy in people with type 2 diabetes: A randomized controlled study." J Diabetes Investig, 2021;12(7):1193-1201. PMID: 33251697.
- [clinical-trial] Raghavan A, et al. "A prospective, multicentre, randomized, open-label comparison of a long-acting basal insulin analog glargine plus glulisine with premixed insulin in insulin naïve patients with Type 2 diabetes - A study from India." Prim Care Diabetes, 2024;18(2):210-217. PMID: 38267312.
- [pubmed] Kawaguchi Y, et al. "Comparison of the efficacy and safety of insulin degludec/aspart (twice-daily injections), insulin glargine 300 U/mL, and insulin glulisine (basal-bolus therapy)." J Diabetes Investig, 2019;10(6):1527-1536. PMID: 30868726.
- [clinical-trial] Kawaguchi Y, et al. "Comparisons of efficacy and safety in insulin glargine and lixisenatide plus glulisine combination therapy with multiple daily injection therapy in Japanese patients with type 2 diabetes." J Diabetes Investig, 2022;13(3):505-514. PMID: 34551215.
- [pubmed] Kordonouri O, et al. "Lipoatrophy in children, adolescents and adults with insulin pump treatment: Is there a beneficial effect of insulin glulisine?." Pediatr Diabetes, 2020;21(7):1285-1291. PMID: 32738019.
- [clinical-trial] Tonneijck L, et al. "Postprandial renal haemodynamic effect of lixisenatide vs once-daily insulin-glulisine in patients with type 2 diabetes on insulin-glargine: An 8-week, randomised, open-label trial." Diabetes Obes Metab, 2017;19(12):1669-1680. PMID: 28449402.
- [fda-pi] Apidra (insulin glulisine) injection US prescribing information (DailyMed set e7af6a7a, effective November 25, 2025), sections 2.2-2.3; read through openFDA October 6, 2026.
Sources & Citations
Studies were read from their PubMed abstracts; the Apidra label from DailyMed (set e7af6a7a, effective November 25, 2025) through openFDA, read October 6, 2026.
Medical Disclaimer: This content is for educational and informational purposes only. It is not medical advice, and nothing here is an instruction to obtain or use any compound. Talk to a licensed clinician about your own situation.