New long-acting insulin product requires fewer shots
The tireless effort aimed at lessening the number of dreaded injections diabetes patients must endure has resulted in the development of yet another long-acting insulin product.
Manufactured by Aventis Pharmaceuticals, Lantus (insulin glargine [rDNA origin] injection) was recently approved for once-daily subcutaneous administration at bedtime in the treatment of adult patients with Type 2 diabetes mellitus (DM) who require basal (long-acting) insulin for the control of hyperglycemia. Additionally, the recombinant human insulin analog product is indicated for adult and pediatric patients with Type 1 DM.
Apparently, the product's long duration of action is derived from its pH. According to Matthew C. Riddle, M.D., insulin glargine remains soluble in the mildly acidic environment of its vial, yet it is insoluble at the neutral pH of subcutaneous tissue. So when injected, the product forms a fine precipitate that is gradually absorbed. "The resulting blood levels from a once-daily injection are nearly constant for approximately 24 hours," observed Riddle, a professor of medicine in the division of endocrinology, diabetes, and clinical nutrition at Oregon Health Sciences University.
In discussing the product's upside, Riddle pointed out that insulin glargine has the benefit of "much less variability in absorption than Ultralente insulin." The product also appears to have the additional advantage over NPH insulin in having a 24-hour action without a sharp peak. According to the labeling of insulin glargine, the median time between injection and the end of pharmacological effect was 14.5 hours for NPH human insulin and 24 hours for insulin glargine. But regardless of the differences in the duration of action, both NPH insulin and insulin glargine have demonstrated similar levels of efficacy with regard to metabolic control.
Acknowledging a considerable disadvantage of insulin glargine, Riddle noted that the product cannot be mixed in a syringe with any other currently available insulin since its pharmacokinetic profile may be altered in an unpredictable manner. This inconvenience is not shared with NPH insulin products, which are available in premixed formulations with regular short-acting insulin.
In discussing the side effect profile, Chris Lynch, Pharm.D., noted that the new insulin's aforementioned "lack of peak may lessen the likelihood of nocturnal hypoglycemia, especially in patients with Type 2 DM, who take a dose of insulin at bedtime." Lynch—an ambulatory care clinical pharmacist at the Medical Center of Louisiana-New Orleans Center for Diabetes Excellence—cautioned, however, that this prospect has not yet been proven and requires further study. The current trials listed in the product labeling did compare the incidence of hypoglycemia between insulin glargine and NPH insulin in both Type 1 and Type 2 diabetes patients, but it was concluded that the overall rate of the complication was similar with both products.
Adverse effects associated with insulin glargine include injection site reactions and immediate-type allergic reactions.
Riddle expects insulin glargine "to quickly replace NPH, Lente, and Ultralente insulins for overnight and between-meal insulin delivery for Type 1 diabetes patients."
Holding a different view, Lynch cautioned that "it is too soon to advocate a wholesale abandonment of NPH insulin in favor of insulin glargine, based solely upon the theoretical advantages of the newer agent." Patients with "documented nocturnal hypoglycemia [a rare event] or patients in whom the erratically absorbed Ultralente insulin may have been preferred—such as those with Type 1 DM who have widely fluctuating glucose levels—are the only candidates on my short list for conversion," he added.
TIPS TO REMEMBER: Lantus
Be aware that the prolonged effect of Lantus may delay recovery from hypoglycemia.
Remind prescribers that when switching from twice-daily NPH insulin to once-daily Lantus, the Lantus dose should be reduced by 20% from the previous total daily NPH dose in order to reduce the risk of hypoglycemia.
Lantus must not be diluted or mixed with any other insulin or solution.
Instruct patients to throw the vial away if the solution inside is cloudy or has particles in it.
Lantus is supplied as 100 units per ml and is available in 5- and 10-ml vials, and in 3-ml cartridges