Also known as: Lantus · Basaglar · Toujeo · long-acting basal insulin
Insulin glargine (Lantus, Basaglar, Toujeo) is a long-acting basal insulin analogue with an elimination half-life of approximately 12–19 hours following subcutaneous injection[1][2], based on FDA NDA 021081 and Heise T et al. (Diabetes Care, 2002). Its defining pharmacokinetic feature is a peakless (flat) action profile that provides approximately 24 hours of basal insulin coverage, enabling once-daily subcutaneous dosing.
| Parameter | Value (SC) | Source |
|---|---|---|
| Elimination Half-Life | ~12–19 hours | Heise T et al. Diabetes Care 2002 (PMID 11815489)[2]; FDA NDA 021081[1] |
| Onset of Action | 1–2 hours | FDA NDA 021081 (Lantus label)[1] |
| Peak Effect | No pronounced peak — essentially peakless (flat profile) | FDA NDA 021081[1]; Heise 2002[2] |
| Duration of Action | ~24 hours (Lantus 100 U/mL); ~36 hours (Toujeo 300 U/mL) | FDA NDA 021081, NDA 205692[1] |
| Bioavailability (SC) | ~70% (estimated) | FDA NDA 021081[1] |
| Full Clearance (5 × t½) | ~60–95 hours | Calculated from Heise 2002 and FDA PK data |
| Time to Steady State | 2–3 days (once-daily dosing) | FDA NDA 021081[1] |
| IV Administration | Not compatible — clear solution but pH 4; IV use contraindicated | FDA NDA 021081[1] |
| Within-Patient PK Variability | ~26% coefficient of variation (vs ~68% for NPH) | Lepore et al. 2000 (PMID 11118018)[3] |
| Standard Dosing Frequency | Once daily SC (any time, same time each day) | FDA NDA 021081 |
| Data Quality | Human RCT — FDA NDA 021081 (Lantus); Heise T et al. Diabetes Care 2002 (PMID 11815489) | |
Insulin glargine has an elimination half-life of approximately 12–19 hours following subcutaneous injection, based on pharmacokinetic data from Heise T et al. (Diabetes Care, 2002; PMID 11815489)[2] and from FDA NDA 021081 (Lantus prescribing information).[1] This half-life — substantially longer than NPH (~4–6 h) and regular insulin (~2 h) — is the pharmacokinetic basis for once-daily dosing as a basal insulin.
The defining pharmacokinetic feature of glargine is not its half-life per se, but its peakless (essentially flat) action profile. Unlike NPH, which has a pronounced peak at 4–8 hours, glargine provides relatively constant insulin delivery throughout the 24-hour dosing interval, closely mimicking the flat basal insulin secretion pattern of a healthy pancreatic beta cell.
Glargine pharmacokinetics are characterised through euglycaemic clamp studies — the gold-standard method for quantifying insulin action. Heise et al. (2002) compared glargine and NPH pharmacokinetics and pharmacodynamics in a crossover clamp study in patients with type 1 diabetes, demonstrating glargine's substantially longer duration and flatter profile vs NPH.[2] The FDA NDA 021081 clinical pharmacology review provides population PK parameters based on data from pivotal clinical trials.
| Layer | Metric | Value | Source |
|---|---|---|---|
| Layer 1 | Plasma half-life | ~12–19 hours | Heise 2002; FDA NDA 021081 |
| Layer 2 | Full plasma clearance (5 × t½) | ~60–95 hours (~2.5–4 days) | Calculated from PK data |
| Layer 3 | Glucose-lowering action duration | ~24 hours (100 U/mL); ~36 hours (300 U/mL Toujeo) | FDA NDA 021081, NDA 205692 |
Glargine's 24-hour glucose-lowering duration arises primarily from the extended SC depot dissolution, not from systemic circulation time. Once absorbed, glargine is metabolised to two active metabolites (M1 and M2) with shorter half-lives. The flat absorption profile from the microprecipitate depot — not prolonged systemic circulation — is what produces the characteristic 24-hour basal coverage.
| Half-Lives Elapsed | Time After SC Injection | % Remaining | Clinical Note |
|---|---|---|---|
| 1 | ~12–19 hours | 50% | Approaching end of primary action window |
| 2 | ~24–38 hours | 25% | Second day; overlap with subsequent daily dose |
| 3 | ~36–57 hours | 12.5% | Accumulation at steady state with daily dosing |
| 4 | ~48–76 hours | 6.25% | Approaching pharmacological clearance |
| 5 (threshold) | ~60–95 hours | ~3% | Near-complete clearance; ~2.5–4 days after last dose |
With once-daily dosing, glargine reaches steady-state plasma concentrations after approximately 2–3 days (2–4 half-lives). At steady state, exposure is approximately 1.5-fold higher than after a single dose, but the flat profile is maintained.[1] Clinicians should be aware that blood glucose–lowering effect may intensify slightly over the first 3 days of therapy as steady state is reached.
Glargine's ~12–19 hour half-life and ~24-hour flat action profile are specifically engineered to enable once-daily subcutaneous dosing as a basal insulin. The peakless action means there is no discrete high-risk hypoglycaemia window (unlike NPH's 4–8 hour peak). Glargine can be injected at any consistent time of day — morning or evening — with comparable glycaemic control outcomes, provided it is taken at the same time each day.[1]
Missing a single glargine dose results in gradual loss of basal insulin coverage beginning approximately 20–24 hours after the last dose. Because the half-life is ~12–19 hours, some residual glucose-lowering effect persists for 2–3 days after the last dose — but insufficient for full glycaemic control. Patients should not attempt to compensate for a missed dose by doubling the next dose without physician guidance.
| Insulin | Brand(s) | Half-Life SC | Profile | Duration | Dosing |
|---|---|---|---|---|---|
| NPH insulin | Humulin N, Novolin N | ~4–6 h | Peaked (4–8 h) | 12–18 h | 1–2× daily |
| Insulin Glargine 100 U/mL | Lantus, Basaglar | ~12–19 h | Peakless | ~24 h | Once daily |
| Insulin Glargine 300 U/mL | Toujeo | ~19 h (est.) | Flatter than 100 U/mL | ~36 h | Once daily |
| Insulin Detemir | Levemir | ~5–7 h | Mild peak | 12–24 h (dose-dependent) | 1–2× daily |
| Insulin Degludec | Tresiba | ~25 h | Ultra-peakless | ≥42 h | Once daily (flexible) |
| Route | Compatibility | Notes |
|---|---|---|
| Subcutaneous (abdomen, thigh, upper arm) | Yes — only approved route | Consistent site rotation within same body region recommended |
| Intravenous (IV) | Contraindicated | Formulated at pH 4 (acidic); IV administration would cause severe acidosis at injection site and unpredictable systemic effects; not approved |
| Intramuscular (IM) | Not recommended | Faster and more erratic absorption than SC; risk of hypoglycaemia; not a standard route |
Insulin glargine is not detected by standard workplace immunoassay drug panels. WADA prohibits non-therapeutic insulin use in sport (S4 — Hormone and Metabolic Modulators). Athletes with diabetes require a Therapeutic Use Exemption (TUE).
Unlike regular human insulin, glargine contains two amino acid modifications (A21 Asn→Gly; two additional Arg at B30-C-terminus) that allow LC-MS/MS differentiation from endogenous insulin in WADA-accredited laboratory testing. Detection in urine is typically feasible within approximately 24 hours of the last dose. The glargine metabolites M1 (des-ThrB30 glargine) and M2 (des-ThrB30-ProB29 glargine) are active and can be detected separately from intact glargine.
Insulin glargine's unique pharmacokinetics arise from two structural modifications relative to human insulin: substitution of asparagine at A21 with glycine (A21 Gly), and addition of two arginine residues at the C-terminus of the B-chain (B31-Arg and B32-Arg).[1] Together these substitutions shift glargine's isoelectric point from ~pH 5.4 (human insulin) to ~pH 6.7.
The formulation is prepared as a clear, slightly acidic solution at pH 4.0. At pH 4, glargine is fully soluble. Upon subcutaneous injection into tissue at physiological pH 7.4, the pH shift drives precipitation of glargine into a microprecipitate depot — a semi-solid aggregate of glargine molecules that forms within minutes of injection at the injection site.[1]
This microprecipitate depot dissolves slowly and continuously at physiological temperature and pH, releasing insulin monomers at a relatively constant rate over approximately 24 hours. The rate of dissolution — not the systemic half-life — governs the duration and profile of glucose-lowering activity. Because dissolution is slow and steady (not burst-like as with NPH hexamer dissociation), the resulting plasma insulin profile is flat rather than peaked.[2]
Toujeo (glargine 300 U/mL) concentrates glargine threefold relative to Lantus. At higher concentration, the SC microprecipitate volume is smaller for the same dose, and the surface-area-to-volume ratio of the depot is lower, slowing dissolution further and producing an even flatter, longer-duration (~36-hour) profile with lower within-patient variability than 100 U/mL glargine.[1]
Log glargine injection times and model the flat 24-hour action window. Identify coverage gaps and overlap periods. Monitor the 2–3 day steady-state build-up when starting or adjusting. On-device. No data shared externally.
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