Insulin Glargine (Lantus, Abasaglar, Semglee, Toujeo) 💉

At a glance

• Class: Long-acting / ultra-long-acting basal insulin analogue
• Molecules: Insulin glargine 100 units/mL (U100) and 300 units/mL (U300)
• Common brands (U100): Lantus®, Abasaglar®, Semglee® (biosimilars)
• Common brand (U300): Toujeo®
• Route: Subcutaneous injection (pre-filled pens)
• Indications: Type 1 and type 2 diabetes as basal insulin in adults, adolescents and children (age cut-offs vary by brand/SPC)
• UK reality: Glargine (especially biosimilars) is a workhorse basal insulin in the NHS and a major destination for patients switched from detemir (Levemir).

What is insulin glargine? 🧬

Insulin glargine is a modified human insulin analogue designed to provide a relatively flat, prolonged basal insulin level over ~24 hours (U100) or longer (U300). Structurally, compared with human insulin:

• A21 asparagine → glycine
• Two arginines added at positions B31 and B32

These changes make glargine less soluble at physiological pH and shift its isoelectric point. It is formulated at an acidic pH (~pH 4) to remain soluble in the pen. Once injected into the neutral pH of subcutaneous tissue, it precipitates into microcrystals and is then slowly re-dissolved, releasing insulin gradually.

Key idea: Detemir and degludec prolong action via albumin binding and multi-hexamers; glargine prolongs action by pH-dependent precipitation in the subcutaneous depot.

How does insulin glargine work? ⏱

• After SC injection: The acidic solution meets neutral tissue pH ⟶ glargine precipitates as a depot of microcrystals.
• Slow dissolution: The depot gradually releases small amounts of soluble glargine into the circulation over many hours.
• Metabolic action: Once in the blood, glargine is converted to active metabolites (e.g. M1) that bind to insulin receptors and:
  • Suppress hepatic glucose output.
  • Increase peripheral glucose uptake in muscle and adipose tissue.
  • Reduce lipolysis and ketogenesis.
• Profile:
  • U100: approx. 24-hour coverage, modest “peak-less” profile.
  • U300: more concentrated, smaller injection volume, flatter and longer profile (>24 h), often with fewer nocturnal hypos.

Indications and role in UK practice 🇬🇧

Clinical indications

• Type 1 diabetes
  • Basal component of basal–bolus regimens (e.g. glargine + rapid-acting insulin at meals).
  • Once daily dosing is standard; occasionally split doses if very high requirements or dawn phenomenon not controlled.
• Type 2 diabetes
  • Basal insulin add-on to oral agents ± GLP-1 RA when HbA1c remains above target.
  • Part of a full basal–bolus regimen in advanced T2DM.

UK formulary context

• Glargine (especially biosimilar U100 preparations) is widely used as a first-line basal analogue when NPH is not suitable or has failed.
• With Levemir being withdrawn, many patients are being switched to:
  • Glargine U100 biosimilar (cost-effective, once daily), or
  • Glargine U300 or degludec in those with troublesome nocturnal hypos or marked variability.
• NICE NG28 places basal insulin (NPH or analogue) as an option when oral therapies and GLP-1 RA are insufficient; local pathways often prefer an NPH-first, glargine-biosimilar second approach in T2DM, balancing cost and hypo risk.

Teaching angle: For exams, glargine is your archetypal once-daily basal analogue, with biosimilars commonly used in the NHS for cost reasons.

Dosing and regimens 💉

General principles

• Administered once daily, usually in the evening or at the same time each day.
• Sites: abdomen, thigh, upper arm, buttock. Emphasise rotation to avoid lipohypertrophy.
• Units of glargine are equivalent in potency to human insulin units (but remember U300 requires different unit–volume relationships on the pen).

Typical starting doses

• Type 2 diabetes (basal add-on)
  • Start at around 10 units once daily or 0.2 units/kg.
  • Increase by 2–4 units every 3–4 days aiming for fasting glucose in target (e.g. 5–7 mmol/L), as long as no hypos.
• Type 1 diabetes (basal–bolus)
  • Total daily insulin often ~0.5–0.7 units/kg/day (all insulins).
  • Basal usually ~40–50% of total daily dose as once-daily glargine.
  • Adjust based on fasting and pre-meal readings and hypo frequency.

Important: U300 (Toujeo) has a flatter, longer profile and usually needs a slightly higher total daily dose than U100 for equivalent effect, with titration over several days.

Pharmacokinetics and dynamics 📈

• U100 (e.g. Lantus, Abasaglar, Semglee)
  • Onset: ~1–2 hours.
  • No sharp peak, but some patients sense a mild mid-curve effect.
  • Duration: ~24 hours in most adults.
• U300 (Toujeo)
  • More concentrated solution; injection volume is smaller.
  • Onset similar but duration >24–30 hours, with a flatter profile.
  • Steady state achieved after several days; dose changes should not be too frequent.
• Variability: Less day-to-day variability than NPH; U300 often even smoother than U100.

Pros and cons ⚖️

Advantages

• Once-daily basal for most patients (especially U100 in T2DM).
• Flatter profile and lower nocturnal hypo risk than NPH in many studies.
• Extensive clinical experience in type 1 and type 2 diabetes, including in children (brand/SPC dependent) and pregnancy under specialist care.
• Biosimilars provide cost savings for the NHS with similar efficacy and safety.

Disadvantages

• Still associated with hypoglycaemia and weight gain – not “hypo-proof”.
• More expensive than NPH (though biosimilars narrow the gap).
• U300 and degludec may be needed in those with recurrent nocturnal hypos or very brittle control, adding complexity.

Adverse effects and safety 🚨

• Hypoglycaemia
  • The major risk of any insulin. Glargine reduces nocturnal hypoglycaemia vs NPH, but hypos still common if doses or other meds are excessive.
  • Patients should know “4 is the floor” (BG <4 mmol/L) and the 15–20 g fast-acting carb rule for treatment.
• Weight gain
  • Improved glycaemic control ⟶ less glucosuria ⟶ weight gain, particularly if diet not adjusted.
• Injection-site issues
  • Lipohypertrophy, pain, redness. Examine sites in clinic; encourage site rotation and good needle technique.
• Allergy
  • Local or systemic allergy is rare but recognised.
• Driving / DVLA
  • Standard insulin rules: regular glucose checks, awareness of hypo symptoms, no driving with BG <5 mmol/L (practical teaching number often used), and compliance with DVLA guidance for group 1 and group 2 licences.

Special situations

Elderly and frail patients

• Often need lower doses due to reduced intake and renal function.
• Targets are usually relaxed (e.g. aiming to avoid hypos rather than strict HbA1c control).
• Once-daily glargine can simplify regimens in care homes and community nursing, but only if CBG monitoring and education are adequate.

Renal and hepatic impairment

• Reduced clearance ⟶ higher risk of hypos.
• No formal dose adjustments in the SPC, but in practice doses should be conservative and titrated slowly with frequent CBG checks.

Peri-operative use

• Basal insulin is usually continued at a reduced dose (often 50–80% of normal) on the day of surgery, depending on local protocol and surgery type.
• Glargine provides background insulin while variable-rate IV insulin is used in major surgery or prolonged fasting.

Switching to or from glargine 🔄

In clinical practice, switching between basal insulins is common – especially with Levemir withdrawal and increased use of biosimilars. Key principles (always follow local guidance in reality):

• From NPH to glargine U100
  • Total up the patient’s daily NPH dose; start glargine at a similar or slightly lower dose (e.g. 80–100%).
  • Reduce more aggressively if high hypo risk (frailty, CKD, recent severe hypo).
• From detemir (once or twice daily) to glargine U100
  • Sum total daily detemir and start glargine U100 at a similar or slightly reduced dose (e.g. ~80–100%).
  • Change to once-daily dosing.
• From glargine U100 to U300
  • Start U300 at the same number of units per day, but expect to need a modest dose increase over time.
  • Titrate slowly (every 3–4 days) based on fasting glucose and hypos.
• To degludec (Tresiba)
  • Often start degludec at the same or slightly lower daily basal units, then titrate.
  • Remember the ultra-long half-life – changes take several days to fully show.

Safety message: In high-risk groups (older adults, CKD, recurrent hypos), always err on the side of a slightly lower starting dose and careful follow-up.

Quick comparison: Basal insulin options

Insulin	Type	Duration	Dosing	Notes
Glargine U100 (Lantus, Abasaglar, Semglee)	Long-acting analogue	~24 h	Once daily	Workhorse basal analogue; biosimilars widely used.
Glargine U300 (Toujeo)	Ultra-long analogue	>24–30 h	Once daily	Flatter profile, fewer nocturnal hypos; often needs slightly higher dose.
Detemir (Levemir)	Long-acting analogue	12–24 h	Once / twice daily	Albumin-bound; now being discontinued.
Degludec (Tresiba)	Ultra-long analogue	>42 h	Once daily	Very stable; flexible timing; often reserved for high-risk or brittle patients.
NPH (Insulatard, Humulin I)	Intermediate-acting	12–18 h	Once / twice daily	Cheaper; more variable; more nocturnal hypoglycaemia.

Key take-home points for students and juniors 🎓

• Insulin glargine is a long-acting basal insulin analogue that works by precipitating at neutral pH in the subcutaneous tissue and slowly dissolving.
• U100 preparations (Lantus, Abasaglar, Semglee) give ~24-hour cover and are commonly used once daily in T1DM and T2DM.
• U300 (Toujeo) is more concentrated with an even flatter, longer profile and fewer nocturnal hypos, but needs careful, gradual titration and slightly higher doses.
• Glargine biosimilars are heavily used in the NHS due to cost-effectiveness and comparable efficacy/safety.
• On the ward, when you see glargine, think “once-daily basal”: review fasting glucose, hypo history, injection sites, driving status, and whether doses are being titrated safely, especially after switches from other basal insulins.