Abasaglar

FDA-Approved Indications:

• Type 1 Diabetes Mellitus (T1DM):
  For once-daily, long-acting basal insulin therapy to improve glycemic control in adults and pediatric patients ≥6 years of age.
• Type 2 Diabetes Mellitus (T2DM):
  Indicated as a once-daily basal insulin to improve glycemic control in adults and pediatric patients ≥6 years of age who require basal insulin for control of hyperglycemia.

Clinically Accepted Off-Label Uses:

• Gestational Diabetes Mellitus (GDM):
  Occasionally used off-label as basal insulin in pregnant women when NPH insulin is unsuitable and under specialist endocrinologist guidance.
• Hyperglycemia in Hospitalized Patients:
  May be used as basal insulin component for persistently uncontrolled hyperglycemia in non-critically ill hospitalized patients receiving basal-bolus regimens.

General:
Administer once daily by subcutaneous injection at the same time each day. Do not mix with other insulins or dilute.

Adults (T1DM):

• Initial total daily insulin dose: ~0.4–0.5 units/kg/day (total basal-bolus regimen).
• ~50% of total daily insulin is given as basal insulin glargine; the remainder as rapid/short-acting insulin divided among meals.
• Dose adjustments based on frequent blood glucose monitoring.

Adults (T2DM):

• Starting dose: 10 units once daily OR 0.2 units/kg once daily.
• Titrate by 2–4 units once or twice weekly to reach individualized fasting plasma glucose targets.

Pediatrics (≥6 years, T1DM):

• Initial dosing: Similar weight-based calculations as adults.
• Adjust carefully; frequent monitoring required due to increased hypoglycemia risk.

Elderly:

• Start conservatively at lower end of dosing range.
• Increased risk of hypoglycemia; monitor renal function regularly.

Renal Impairment:

• Reduced insulin clearance may require lower doses.
• Frequent blood glucose monitoring and conservative titration recommended.

Hepatic Impairment:

• Insulin requirements may be lower due to reduced hepatic glucose output.
• Frequent monitoring and gradual titration necessary.

Administration Details:

• Subcutaneous injection only.
• Preferred sites: abdomen, thigh, or upper arm; rotate sites within same region to reduce risk of lipodystrophy.
• Must not be administered intravenously or used in insulin pumps.

Insulin glargine is a human insulin analog with amino acid substitutions that shift its isoelectric point, making it less soluble at physiological pH. After subcutaneous injection, it precipitates in the subcutaneous tissue, forming a depot from which insulin is gradually released. This provides a steady, peakless basal insulin level over approximately 24 hours. It binds to insulin receptors on muscle and adipose cells, promoting glucose uptake and storage as glycogen, while inhibiting hepatic gluconeogenesis and lipolysis, thereby lowering blood glucose levels throughout the day and overnight.

• Absorption: Forms microprecipitates in subcutaneous tissue with slow, consistent dissolution.
• Onset: ~1.5–2 hours.
• Peak: No pronounced peak; provides steady basal action.
• Duration: ~24 hours (range: 18–26 hours; duration may be longer at higher doses).
• Bioavailability: ~60%.
• Distribution: Limited data; acts locally at injection site before systemic distribution.
• Metabolism: Metabolized by proteolytic cleavage to M1 (main active metabolite) and M2 (minor inactive metabolite).
• Excretion: Primarily renal elimination of peptides/metabolites.
• Half-life: Apparent terminal half-life ~12 hours, governed by slow absorption rather than plasma clearance.

Pregnancy:

• Insulin glargine is not assigned an FDA pregnancy category under the current labeling; however, available human data have not shown increased fetal harm when used as indicated.
• Insulin requirements vary during pregnancy and postpartum; frequent monitoring and dose adjustments are mandatory.

Lactation:

• Insulin glargine is excreted into breast milk in minimal amounts, but it is destroyed in the infant’s GI tract and does not cause clinically significant effects.
• Breastfeeding is considered safe; monitor maternal glucose closely postpartum.

• Class: Long-acting human insulin analog
• Subclass: Recombinant DNA origin basal insulin

• Known hypersensitivity to insulin glargine or any excipients in the formulation
• During episodes of clinically significant hypoglycemia
• Use in insulin pumps or intravenous administration is contraindicated

• Hypoglycemia: Major risk; risk factors include skipping meals, excessive dose, or increased activity. Monitor closely, educate patients on signs/symptoms.
• Insulin Regimen Changes: Switching from another basal insulin may require dose adjustments to avoid hypo/hyperglycemia.
• Renal/Hepatic Dysfunction: Use with caution; both may reduce insulin clearance, increasing hypoglycemia risk.
• Fluid Retention/Heart Failure: Caution when co-administered with thiazolidinediones (TZDs); can cause fluid retention and exacerbate heart failure.
• Hypokalemia: May cause or worsen hypokalemia; monitor serum potassium if clinically indicated.
• Injection Site Reactions: Rotate sites to minimize lipohypertrophy.
• Hypersensitivity Reactions: Rare systemic allergy or anaphylaxis possible; discontinue if severe.

Common (by system):

• Metabolic: Hypoglycemia (most frequent adverse reaction)
• General: Weight gain (dose-dependent)
• Injection Site: Redness, itching, swelling, lipodystrophy

Serious or Rare:

• Severe hypoglycemia causing seizures, coma
• Systemic allergic reactions/anaphylaxis (rare)
• Hypokalemia (risk increased with high doses or concomitant diuretics)

Timing:

• Hypoglycemia risk highest overnight or during fasting periods; onset within a few hours, sustained if not treated.

Increased Hypoglycemia Risk:

• Oral antidiabetic drugs (e.g., sulfonylureas, meglitinides)
• Beta-blockers (may mask hypoglycemia symptoms)
• MAO inhibitors, ACE inhibitors, salicylates

Decreased Insulin Efficacy:

• Corticosteroids, diuretics, thyroid hormones, sympathomimetics (may increase glucose)

Alcohol:

• May potentiate or prolong hypoglycemia due to inhibition of gluconeogenesis.

Enzyme Systems:

• Not CYP450-mediated, but glucose metabolism may be indirectly affected by drugs acting through CYP450 pathways.

• Biosimilar glargine products (e.g., Basaglar, Semglee) approved in the US/EU to increase access.
• Recent diabetes guidelines (ADA, EASD, NICE) continue to recommend long-acting insulin analogs like glargine as preferred basal insulin for lower nocturnal hypoglycemia risk versus NPH.
• No major FDA or EMA label changes recently regarding new safety concerns.

• Unopened vials/pens: Refrigerate at 2°C–8°C (36°F–46°F). Do not freeze.
• In-use vials/pens: May be kept at room temperature (up to 25°C–30°C) and used within 28 days.
• Light/Humidity: Protect from direct heat and light.
• Handling: Do not shake vigorously. Do not mix with other insulins or dilute.