Insulin glargine

Summary

Insulin glargine is a long‑acting insulin analogue approved for subcutaneous use in the treatment of diabetes mellitus. It provides a basal insulin level to control fasting glucose and is commonly used in type 1 and type 2 diabetes, as well as in specific acute settings such as diabetic ketoacidosis (DKA). It is administered once daily and is available under several brand names, including Lantus, Toujeo and Basaglar, reflecting different concentrations.

Mechanism of Action

Insulin glargine is a recombinant human insulin analogue in which the amino‑acid sequence is modified to alter its solubility profile. After subcutaneous injection it forms micro‑precipitates that release insulin slowly, providing a relatively constant plasma concentration for about 24 hours. The molecule binds the insulin receptor on muscle, adipose and hepatic cells, activating the receptor tyrosine kinase cascade, which promotes glucose uptake, glycogen synthesis and inhibition of hepatic glucose production, thereby lowering blood glucose.

What the Research Shows

Evidence for insulin glargine comes from several recent clinical investigations. In a single‑centre randomised trial of 60 adults with diabetic ketoacidosis, adding a single subcutaneous dose of insulin glargine (0.3 U/kg) to standard intravenous insulin shortened the time to DKA resolution (≈10 h vs 13 h) and reduced hospital length of stay without increasing hypoglycaemia or hypokalaemia. A broader systematic review and network meta‑analysis of 44 phase‑III trials (23 699 participants) comparing basal insulins found no significant differences in HbA1c reduction among insulin glargine, detemir, degludec and NPH. However, the 300 U/mL formulation of insulin glargine (IGlar‑300) was associated with modestly less weight gain (≈3–4 kg) and lower odds of overall and nocturnal hypoglycaemia compared with NPH and some other basal agents. A recent meta‑analysis of eight randomised DKA trials (468 participants) confirmed that early subcutaneous basal insulin, including insulin glargine, accelerates DKA resolution and reduces total intravenous insulin requirements, with safety outcomes comparable to standard therapy.

Reported Benefits

Insulin glargine provides a once‑daily basal insulin that reliably lowers fasting glucose and, in acute DKA, early use speeds metabolic recovery and shortens hospital stay. In comparative trials, it achieves HbA1c reductions similar to other basal insulins. The 300 U/mL formulation tends to produce less weight gain and carries a lower risk of overall and nocturnal hypoglycaemia than NPH insulin, offering a safety advantage for patients prone to low blood sugars.

Limitations of the Evidence

While the data support insulin glargine’s efficacy, several gaps remain. The DKA trials involved modest sample sizes and were conducted at single centres, limiting generalisability. The network meta‑analysis indicated low to very low certainty for the weight‑gain advantage of IGlar‑300, reflecting indirect comparisons and heterogeneity among studies. Long‑term outcomes such as cardiovascular events were not addressed in the cited reports. Moreover, differences between insulin glargine concentrations (100 U/mL vs 300 U/mL) were not directly compared in head‑to‑head trials within the presented literature.

Safety Considerations

The randomized DKA study reported similar rates of hypoglycaemia and hypokalaemia between early insulin glargine plus intravenous insulin and standard intravenous insulin alone, indicating no excess safety risk. The broader basal‑insulin network analysis found that insulin glargine, particularly the 300 U/mL formulation, had lower odds of overall, nocturnal and severe hypoglycaemia compared with NPH insulin. No new adverse events were identified in the meta‑analysis of early basal insulin use in DKA, and mortality was comparable between groups. Overall, the safety profile of insulin glargine appears comparable to other basal insulins, with a possible advantage in reducing hypoglycaemia.

How It Is Administered

Insulin glargine is administered by subcutaneous injection, typically once daily. It is supplied in pre‑filled pens or vials at concentrations of 100 U/mL (e.g., Lantus) and 300 U/mL (e.g., Toujeo). The formulation creates a subcutaneous depot that releases insulin slowly over 24 hours.

Routes of Administration

Goals & Uses

• Basal insulin replacementPhysiologicHigh
• Weight management (relative)MetabolicModerate
• Glycemic controlDiabetesHigh
• Reduction of hypoglycemia risk vs. NPH insulinSafety / TolerabilityHigh
• Glycemic control in type 1 diabetes mellitusEndocrine / MetabolicHigh
• Gestational diabetes / diabetes in pregnancyGlycemic ManagementModerate
• Glycemic control in type 2 diabetes mellitusEndocrine / MetabolicHigh

Contraindications

• Known hypersensitivity to insulin glargine or any excipientAllergyHigh
• IV or IM administrationRoute Of AdministrationHigh
• Hypoglycemic episodes (active)MetabolicHigh
• HypoglycemiaMetabolicHigh
• Hypersensitivity to insulin glargine or excipientsImmunologicalHigh

Adverse Effects

• Visual disturbances / retinopathy worseningOphthalmologicalUncommon
• EdemaFluid BalanceUncommonSwelling from fluid retention
• HypoglycemiaMetabolicCommonAbnormally low blood glucose
• Peripheral edemaFluid BalanceUncommonSwelling of the arms or legs
• Injection site reactionsLocalCommon
• Allergic reactions / anaphylaxisImmunologicRare
• Weight gainMetabolicCommonIncrease in body weight
• LipodystrophyDermatologicRare
• Injection‑site reactionLocalUncommon

Drug Interactions

• Thiazolidinediones (e.g., pioglitazone)Moderate
• Other antidiabetic agents (e.g., sulfonylureas, meglitinides)High
• Beta‑blockersModerate
• Beta-blockersModerate
• Oral antidiabetic agents (sulfonylureas, meglitinides)Moderate
• AlcoholModerate
• CorticosteroidsModerate
• Sympathomimetics (epinephrine, salbutamol)Low

Population Constraints

• PregnancyReproductive SafetyRelative
• Hepatic impairmentOrgan FunctionRelative
• Renal impairmentOrgan ImpairmentRelative
• ElderlyAgeRelative
• Elderly patientsAgeRelative
• Pediatric patients < 6 years (Toujeo 300 U/mL)AgeAbsolute

Regulatory Status

• European UnionApprovedApproved: type 1 diabetes mellitus, type 2 diabetes mellitusEMA approval for both concentrations.
• United StatesApprovedApproved: type 1 diabetes mellitus, type 2 diabetes mellitusFDA approved; Lantus (100 U/mL) 2000, Toujeo (300 U/mL) 2015.
• United KingdomApprovedApproved: type 1 diabetes mellitus, type 2 diabetes mellitusMHRA approval; same indications as EU.

Approved in multiple jurisdictions for basal insulin therapy; available in 100 U/mL (Lantus) and 300 U/mL (Toujeo) formulations.

Evidence & Sources

• Effectiveness and safety of early insulin glargine administration in combination with continuous intravenous insulin infusion in the management of diabetic ketoacidosis: A randomized controlled trial
  Journal ArticleModerateThammakosol K, Sriphrapradang C2023-01-01T00:00:00.000000Z
• Efficacy and safety of basal insulins in people with type 2 diabetes mellitus: a systematic review and network meta-analysis of randomized clinical trials
  Journal ArticleHighDehghani M, et al.2024-01-01T00:00:00.000000Z
• Early subcutaneous basal insulin with intravenous insulin infusion for diabetic ketoacidosis management: A systematic review and meta-analysis of randomised controlled trials
  Journal ArticleHighThammakosol K, et al.2026-01-01T00:00:00.000000Z
• Semaglutide for type 2 diabetes mellitus: A systematic review and meta-analysis
  Journal ArticleHighAndreadis P, et al.2018-01-01T00:00:00.000000Z
• Safety issues of tirzepatide (pancreatitis and gallbladder or biliary disease) in type 2 diabetes and obesity: a systematic review and meta-analysis
  Journal ArticleHighZeng Q, et al.2023-01-01T00:00:00.000000Z

Frequently Asked Questions