LANTUS® (insulin glargine) injection 100 Units/mL

CV Evaluation from the ORIGIN Trial over 6.2 Years (N=12,537)

Limitations:

Metformin was used by 47% of the insulin-glargine group and 60% of the standard-care group which may have been cardioprotective.

Graphic showing two co-primary endpoints. The left side shows the first co-primary endpoint: “Time to first occurrence of a major CV event,” circled by CV Death, Nonfatal MI, and Nonfatal Stroke. The right side shows the second co-primary endpoint: “Time to first occurrence of a CV event,” circled by CV Death, Nonfatal MI, Nonfatal Stroke, Hospitalization for HF, and Revascularization Procedure. The central objective states: “To demonstrate whether Lantus significantly lowers the risk of major CV outcomes vs. standard care.” The acronym ORIGIN (Outcome Reduction with Initial Glargine Intervention) is mentioned at the bottom.

The trial involved people who were not normally prescribed insulin and in whom insulin glargine was used to achieve fasting plasma glucose levels much lower than those typically achieved with insulin therapy. However, the effect in participants with and those without diabetes was similar.
The trial was designed to test the effect of using titrated basal insulin to control glucose levels vs standard-care with guideline-suggested degrees of glycemic control; the trial was specifically not designed to test more intense vs less intense glucose lowering.

No statistically significant differences between Lantus and standard care in the co-primary endpoints

The left graph represents the first co-primary endpoint: time to first occurrence of a major cardiovascular (CV) event, including CV death, nonfatal MI, or nonfatal stroke, with a p-value of 0.63. The right graph shows the second co-primary endpoint: the above outcomes plus revascularization or hospitalization for congestive heart failure, with a p-value of 0.27. The Lantus line is shown in blue, and the standard care line is in gray. The y-axis indicates the proportion with events, and the x-axis shows years of follow-up from 0 to 7.

Similar results were observed between Lantus and standard care for all cause mortality

Mean A1C over 6.2 years (median)

Bar graph with mean A1C (%) on the y-axis. Baseline and Trial end are on the x-axis. Baseline bar shows 6.5% with an arrow stating “6.2 years follow-up” pointing to the right. Trial end has 2 bars. Blue Lantus bar with 6.5% and Standard of care with 6.8% in a gray bar.

Safety results

A table with Lantus® versus standard care in a clinical study. Shows incidence of severe symptomatic hypoglycemia: Lantus® (n=6231) had 349 patients (5.6%) affected with +1.6 effect on weight, while standard care (n=6273) had 113 patients (1.8%) affected with -0.5 effect on weight. A note under indicates hypoglycemia is the most common adverse event with insulin therapies, with severe cases defined as requiring assistance and meeting specific glucose criteria

Study Design

A randomized study of patients with IFG (Impaired fasting glucose) and/or IGT (Impaired glucose tolerance) or early type 2 diabetes mellitus and established CV disease or CV risk at baseline. Patients received either Lantus (n=6264) titrated to a target FPG of ≤95 mg/dL or standard care (n=6273). Standard care patients remained on their original treatment, if applicable, at randomization. Additional agents could be added as needed at the discretion of the investigator. The co-primary outcomes were nonfatal myocardial infarction, nonfatal stroke, or death from cardiovascular causes and these events plus revascularization or hospitalization for heart failure. Microvascular outcomes, incident diabetes, hypoglycemia, weight, and cancers were also compared between groups. Median follow-up: 6.2 years.

Important Safety Information

Important Safety Information for Lantus (insulin glargine injection) 100 Units/mL

Contraindications
Lantus is contraindicated during episodes of hypoglycemia and in patients with hypersensitivity to insulin glargine or any of the excipients in LANTUS.

Warnings and Precautions
Insulin pens, needles, or syringes must never be shared between patients. Do NOT reuse needles.
Monitor blood glucose in all patients treated with insulin. Modify insulin regimen only under medical supervision. Changes in insulin regimen including, strength, manufacturer, type, injection site or method of administration may result in the need for a change in insulin dose or an adjustment in concomitant drugs.

Repeated insulin injections into areas of lipodystrophy or localized cutaneous amyloidosis may result in hyperglycemia; sudden change in the injection site (to unaffected area) has been reported to result in hypoglycemia. Advise patients to rotate injection site to unaffected areas and closely monitor for hypoglycemia.

Do not dilute or mix Lantus with any other insulin or solution. If mixed or diluted, the solution may become cloudy, and the onset of action/time to peak effect may be altered in an unpredictable manner. Do not administer Lantus via an insulin pump or intravenously because severe hypoglycemia can occur.

Hypoglycemia is the most common adverse reaction of insulin therapy, including Lantus, and may be life-threatening.

Hypoglycemia due to medication errors, such as accidental mix-ups between basal insulin products and other insulins, particularly rapid-acting insulins, have been reported. Patients should be instructed to always verify the insulin label before each injection.

Severe life-threatening, generalized allergy, including anaphylaxis, can occur. Discontinue Lantus, treat and monitor until symptoms resolve.

A reduction in the Lantus dose may be required in patients with renal or hepatic impairment.

As with all insulins, Lantus use can lead to life-threatening hypokalemia. Untreated hypokalemia may cause respiratory paralysis, ventricular arrhythmia, and death. Closely monitor potassium levels in patients at risk of hypokalemia and treat if indicated.

Fluid retention, which may lead to or exacerbate heart failure, can occur with concomitant use of thiazolidinediones (TZDs) with insulin. These patients should be observed for signs and symptoms of heart failure. If heart failure occurs, dosage reduction or discontinuation of TZD must be considered.

Drug Interactions
Certain drugs may affect glucose metabolism, requiring insulin dose adjustment and close monitoring of blood glucose. The signs of hypoglycemia may be reduced in patients taking anti-adrenergic drugs (e.g., beta-blockers, clonidine, guanethidine, and reserpine).

Adverse Reactions
Adverse reactions commonly associated with Lantus include hypoglycemia, allergic reactions, injection site reactions, lipodystrophy, pruritus, rash, edema and weight gain.

Important Safety Information for Lantus SoloSTAR

Lantus SoloSTAR is a disposable single-patient-use prefilled insulin pen. To help ensure an accurate dose each time, patients should follow all steps in the Instruction Leaflet accompanying the pen: otherwise they may not get the correct amount of insulin, which may affect their blood glucose.

Indication

Indication and Use
LANTUS is a long-acting human insulin analog indicated to improve glycemic control in adult and pediatric patients with diabetes mellitus.

Limitations of Use
Lantus is not recommended for the treatment of diabetic ketoacidosis.

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Important Safety Information

Indication

References:
1. Lantus Prescribing Information.
2. Origin Trial Investigators, Gerstein H, Yusuf S, Riddle MC, Ryden L, Bosch J. Am Heart J. 2008;155(1):26-32.e326.
3. ORIGIN Trial Investigators, Gerstein HC, Bosch J, et al. N Engl J Med. 2012;367(4):319-328.

Demonstrated Long-Term CV Safety Data In The Landmark Origin Trial1-3* For Lantus® (insulin glargine) injection 100 Units/mL

CV Evaluation from the ORIGIN Trial over 6.2 Years (N=12,537)

No statistically significant differences between Lantus and standard care in the co-primary endpoints

Mean A1C over 6.2 years (median)

Safety results

Study Design

Important Safety Information

Important Safety Information for Lantus (insulin glargine injection) 100 Units/mL

Important Safety Information for Lantus SoloSTAR

Indication

Important Safety Information

Indication

Demonstrated Long-Term CV Safety Data In The Landmark Origin Trial^1-3* For Lantus^® (insulin glargine) injection 100 Units/mL