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Lantus®: Mechanism of Action Video Transcript

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Mechanism of Action

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Voiceover: All known insulins are composed of two polypeptide chains that are linked to one another by

disulfide bonds. Lantus® differs from human insulin in that the physiochemical properties have been

modified.

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Voiceover: The amino acid asparagine at the position A21 is replaced by glycine and two arginines are

added to the C terminus of the B chain.

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Voiceover: The effect of these changes is to shift the isoelectric point, producing a solution that is

completely soluble at pH 4.

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Voiceover: When injected into the subcutaneous tissue, which has a physiologic pH of 7.4, the acidic

solution is neutralized.

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Voiceover: This leads to the formation of micro precipitates, from which small amounts of Lantus® are

slowly released. Insulin crystals exist in hexamer form.

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Voiceover: When micro precipitates develop, the hexamer is subdivided into three dimers, each of which

divides into two monomers.

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Voiceover: This slow dissolution of free hexamers results in a relatively constant concentration time

profile over 24 hours with no pronounced peak. This profile is what allows Lantus® to be dosed once

daily as a patient's basal insulin.

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Lantus® (insulin glargine [rDNA origin] injection)

Proven HbA1c control

See how Lantus® provides effective, improved glycemic control in diabetes patients.

Lantus® Prescribing Information. February 2015.

Once-daily dosing

Lantus® is a once-daily, long-acting insulin.**

**Lantus® Prescribing Information. February 2015.

Demonstrated long-term CV safety

Lantus® is a basal insulin with demonstrated long-term CV safety data††

††Including CV death, nonfatal MI, nonfatal stroke, revascularization, or hospitalization for heart failure. No difference was observed between Lantus® and standard of care in overall incidence of CV death, nonfatal MI, or nonfatal stroke. No difference was observed between treatment groups for death of any cause.