Insulin glargine (Lantus®)
Drug class: Hormone (recombinant human insulin or insulin analog)
Mechanism of Action
Insulin glargine (IGlr), a recombinant human insulin analog (21A-Gly-30Ba-L-Arg-30Bb-L-Arg-; HOE 901), helps regulate glucose metabolism. It binds to insulin receptors, a tyrosine kinase receptor, triggering a conformational change in the intracellular beta catalytic domains. This induces autophosphorylation and recruits docking proteins, including phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K), activating an intracellular signalling cascade that activates protein kinase B (Akt). Akt regulates glucose transporter type 4 (GLUT4), mitogen-activated protein kinases (MAPK), protein kinase C (PKC), and the mitogen-activated pathway (1,2).
IGlr, designed by substituting glycine with arginine, raises the isoelectric point and allows gradual absorption from subcutaneous tissue into the bloodstream, providing long-term action over 24 hours. It enhances peripheral glucose uptake and protein synthesis while inhibiting hepatic glucose production, lipolysis and proteolysis (1, 2)
Approved Indications
Adults and children with Type 1 diabetes mellitus (2)
Adults with Type 2 diabetes mellitus (2)
Dosage and Administration
Subcutaneous (SC) injection: 100 units/mL (U-100) (2)
SC once daily; same time every day, rotate sites, avoid mixing with other insulin/solution (2)
Individualised dosage available based on blood glucose monitoring, glycemic control, metabolic needs, and type of diabetes before insulin use (2)
Key clinical benefits
Improved Glycemic control – lowered HbA1c (2)
Reduction in fasting blood glucose (FBG) (2)
Lower nocturnal hypoglycaemia (2)
Reduced weight gain (2)
Key clinical studies
ORIGIN
In this landmark, randomized 6.2 year study, 12,537 patients (≥75 years) with dysglycaemia, type 2 diabetes mellitus (T2DM), and cardiovascular risk factors received insulin glargine (IGlr) or standard care, alongside n 3 fatty acids. Long term use of insulin glargine achieved durable near normal glycemic control, with HbA1c maintained close to target and fasting blood glucose consistently ≤95 mg/dL. Importantly, insulin glargine demonstrated cardiovascular neutrality (HR 1.00; 95% CI, 0.88–1.13; p=0.97), with no increase in cancer incidence (3).
In participants with impaired fasting glucose or impaired glucose tolerance, insulin glargine also delayed progression to overt diabetes, underscoring its preventive potential. Importantly, the therapy was associated with a low risk of severe hypoglycemia, reinforcing its safety even in older, high risk populations. Cardiovascular outcomes showed neutral impact on major events, offering strong reassurance for long term insulin therapy, while cancer incidence remained unchanged, addressing a key concern with insulin use. Together, these findings established insulin glargine as a safe and effective option for early intervention in dysglycaemia and type 2 diabetes, combining durable efficacy with long term safety (3).
ASIA and GOAL
Real‑world evidence (RWE) from post‑hoc analyses, including the FINE ASIA and GOAL studies, evaluated the effectiveness of insulin glargine (IGlr) in insulin‑naïve patients with type 2 diabetes mellitus (T2DM) in India. After six months of treatment, patients experienced significant improvements in glycemic parameters, with HbA1c reduced by −2.07 (±1.4)% and fasting plasma glucose (FPG) lowered by −94.4 (±65.2) mg/dL. Importantly, these benefits were achieved with a low risk of hypoglycemia and no associated weight gain, reinforcing the safety and efficacy of insulin glargine in the management of T2DM in real‑world Indian practice (4).
DosInGlar Study
A real‑world evidence (RWE) observational, retrospective cohort study analyzed 556 matched adult pairs of insulin‑naïve patients with type 2 diabetes mellitus (T2DM) registered in the Big‑Pac® database (Real Life Data). Patients were treated 1:1 with insulin glargine U100 (IGlr‑100) or insulin glargine U300 (IGlr‑300), with both cohorts matched for age, diabetes duration, insulin dose, weight, and baseline blood glucose levels. Over 18 weeks, both groups achieved a similar and clinically meaningful reduction in HbA1c, confirming the effectiveness of insulin glargine in real‑world practice. Notably, while the IGlr‑300 cohort required a 12.8% higher insulin dose, the comparable glycemic outcomes highlight the robust efficacy and safety of insulin glargine therapy in routine care settings (5).
ELEMENT 1 & 2 Trials
ELEMENT 1 was a randomized, phase 3 trial involving 535 patients with type 1 diabetes mellitus (T1DM) treated with once‑daily basal and bolus insulin. Participants received LY2963016 insulin glargine (Basaglar), a follow‑up biologic of insulin glargine (IGlr), plus pre‑meal insulin lispro for 52 weeks (6). ELEMENT 2 was a similar randomized, phase 3, 24‑week study in 756 patients with type 2 diabetes (T2DM) who were insulin‑naïve or previously treated with insulin glargine or ≥2 oral antidiabetic agents (OAA) (7). In both studies, the primary efficacy outcome of HbA1c reduction was met, with LY IGlr showing non‑inferior results compared to IGlr (Element 1: −0.35 vs −0.46%; Element 2: −1.29 vs −1.34%; p > 0.05). Safety outcomes at 52 weeks were comparable, including adverse events, allergic reactions, hypoglycemia, insulin antibodies, and weight change. These findings confirmed LY IGlr as a cost‑effective, safe, and effective alternative for both T1DM and T2DM (6,7).
ELEMENT 5 Trial
ELEMENT 5 was a randomized, controlled, phase 3, 24 week study in 493 patients with T2DM who were insulin naïve or on basal insulin plus ≥2 OAAs. LY IGlr achieved a similar reduction in HbA1c (−1.25%) compared with IGlr (−1.22%), with a least squares mean difference of −0.04% (95% CI −0.22, 0.15). The biosimilar met the primary efficacy endpoint and demonstrated comparable safety, including adverse events, nocturnal hypoglycemia, insulin antibody response, and weight gain (8).
Common Adverse Events
Allergic reactions (2)
Edema (2)
Hypoglycemia due to medication errors or change in insulin regimen (2)
Injection site reactions (2)
Lipodystrophy (2)
Pruritus (2)
Rash (2)
Weight gain (2)
Hypersensitivity Reactions
Hypokalemia
Contraindications
Hypoglycemia (2)
Hypersensitivity (2)
Special Notes for Clinician
Close medical supervision for hypoglycaemia/hyperglycaemia upon a patient’s change in insulin regimen (2)
Advise a new injection site in case of lipodystrophy or localized cutaneous amyloidosis: monitor for hypoglycaemia (2)
Screening: Rule out hypersensitivity, recurrent hypoglycaemia due to diabetic neuropathy, long-standing diabetes or renal or hepatic impairment (2)
Monitor potassium levels: Avoid in patients at risk for hypokalemia (2)
Fluid Retention and heart failure with concomitant use of peroxisome proliferator-activated receptor (PPAR)-gamma agonists: Avoid thiazolidinediones (TZDs) in combination with insulin. In case of heart failure, manage with the standard of care; discontinue or reduce the dose of the PPAR-gamma agonist (2)
Abbreviations
IGlr: insulin glargine; PI3K: phosphatidylinositol-4,5-bisphosphate 3-kinase; Akt: protein kinase B (Akt); GLUT4: glucose transporter type 4, MAPK: mitogen-activated protein kinases; PKC: protein kinase C; and the mitogen-activated pathway; T1DM: Type 1 diabetes mellitus; T2DM: Type 2 diabetes mellitus; RWE: real world evidence; HbA1C: glycosylated haemoglobin; FBG: fasting blood glucose; FPG: fasting plasma glucose; OAAs: oral antidiabetic agents; PPAR: peroxisome proliferator-activated receptor.
References
Glargine Insulin. Available at: https://www.ncbi.nlm.nih.gov/books/NBK557756/ Accessed on 19 September 2026.
LANTUS (Insulin glargine) prescribing information. Available at:
https://products.sanofi.us/Lantus/Lantus.pdf Accessed on 19 September 2026.
ORIGIN Trial Investigators. Basal insulin and cardiovascular and other outcomes in dysglycemia. N Engl J Med. 2012; 367(4), 319-328.
Deshmukh V, Chaudhury T, Chadha M, et al. LIVE INDIA: Effectiveness of gla-100 in a post hoc pooled analysis of FINE ASIA and GOAL Registries. Diabetes Ther. 2023;14(12):2075-2088.
Duque N, Artime E, Romera I, et al. Real-World Use of Insulin Glargine U100 and U300 in Insulin-Naïve Patients with Type 2 Diabetes Mellitus: DosInGlar Study. Adv Ther. 2021; 38(7):3857-3871
Blevins TC, Dahl D, Rosenstock J, et al. Efficacy and safety of LY2963016 insulin glargine compared with insulin glargine (Lantus®) in patients with type 1 diabetes in a randomized controlled trial: the ELEMENT 1 study. Diabetes Obes Metab. 2015;17(8):726-33.
Rosenstock J, Hollander P, Bhargava A, et al. Similar efficacy and safety of LY2963016 insulin glargine and insulin glargine (Lantus®) in patients with type 2 diabetes who were insulin‐naïve or previously treated with insulin glargine: a randomized, double‐blind controlled trial (the ELEMENT 2 study). Diabetes Obes Metab. 2015;17(8):734-41.
Pollom RK, Ilag LL, Lacaya LB, et al. Lilly Insulin Glargine Versus Lantus® in Insulin-Naïve and Insulin-Treated Adults with Type 2 Diabetes: A Randomized, Controlled Trial (ELEMENT 5). Diabetes Ther. 2019;10(1):189-203.
About the Author
Jaimee George holds a PhD in Microbiology and has published extensively in peer reviewed journals. As a scientific writer, she has developed systematic reviews, book chapters, review articles, and original research papers. Her professional interests include regulatory writing, medical communication tools, and case report development.
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