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Lantus (insulin glargine) Not Only for Bedtime?

May 28, 2003
 

Physicians are pursuing several different possibilities of dosing that deviate from the FDA-approved instructions for Lantus dosing.

Lantus is approved only for bedtime dosing. That’s because the pre-approval studies were conducted only using bedtime dosing, therefore the FDA approved the drug that way.

 

But from experience, patients can also use Lantus in the morning.

Lantus is a “peakless” insulin…giving steady concentrations throughout the day. But for some patients, it doesn’t last the full 24 hours. Morning dosing might be preferred for these patients. That way, Lantus wears off at night when insulin requirements are lower. Some patients use BID dosing if Lantus doesn’t last all day. Explain that the big advantage to Lantus is once daily dosing.

Lantus (insulin glargine) is a recombinant human insulin analog with a duration of action up to 24 hours.1 The microprecipitates that are formed in the subcutaneous tissue after injection slow the absorption of Lantus and provide a relatively constant level of insulin over 24 hours without a pronounced peak.1 This prolonged effect over 24 hours enables it to be administered once daily.

Lantus is FDA approved for once-daily subcutaneous administration at bedtime for adults and children six years of age and older with type 1 diabetes mellitus or adults with type 2 diabetes mellitus who require basal (long-acting) insulin for the control of hyperglycemia.1

When changing a patient (child >6 years or adult) from intermediate- or long-acting insulin to Lantus, the amount of short-acting insulin or oral antidiabetic agent may need to be adjusted. In premarketing studies, for patients using once-daily NPH or Ultralente insulin, the initial dose of Lantus was not changed. For patients using twice-daily NPH insulin, the initial once-daily, bedtime dose of Lantus was reduced by 20% and then adjusted based on the patient’s response.1

The pharmacokinetics of Lantus allows insulin to be released at steady concentrations throughout the day for up to 24 hours.1 This “peakless” effect suggests that Lantus may not only be given daily at bedtime as indicated by the FDA, but alternatively, once daily in the morning or afternoon. The duration of effect of Lantus is prolonged compared to NPH human insulin. The median time between injection and the end of the pharmacological effect for NPH human insulin is 14.5 hours (range: 9.5 to 19.3) and 24 hours for Lantus (range: 10.8 to >24 hours). This wide range with Lantus suggests that the duration of action in some patients may not last as long as 24 hours. Therefore, some patients may require twice-daily dosing of Lantus in order to control the early elevations in blood sugar prior to the next dose. Physicians are pursuing several different possibilities of dosing that deviate from the FDA-approved instructions for Lantus dosing.

The package insert for Lantus states that it should be administered once daily at bedtime. However, this product does exhibit a relatively constant glucose-lowering profile over 24 hours, and therefore in theory, time of dosing should not matter if administered at the same time daily. Since all the clinical trials with Lantus were administered at bedtime, the FDA required the package labeling to reflect that dosing time.

An open-label, parallel group study, on file with Aventis, in type 1 diabetes mellitus adults investigated the effects of Lantus on glycemic control. Patients were randomized to receive a once daily subcutaneous injection of Lantus before breakfast, before dinner, or at bedtime for 24 weeks. Percentage of patients achieving HbA1c goal <7% was similar for all three groups of Lantus, independent of the timing of administration. The 24-hour blood glucose profiles were similar in each treatment group. Additionally, a higher percentage of patients who took Lantus at dinner achieved pre-injection blood glucose levels of

A randomized, controlled, open-label 28-week study, on file with Aventis, compared the efficacy and safety of once daily Amaryl with Lantus administered in the morning or bedtime, or NPH insulin at bedtime in type 2 diabetes patients.2 Patients treated with Lantus in the morning had a statistically significant reduction in HbA1c when compared to both bedtime Lantus and bedtime NPH treated patients.

The results of both of these studies suggest that administering Lantus before breakfast or evening may work just as well, and in some cases better than, administering Lantus at bedtime. Advise patients to monitor their blood glucose if they switch to a different time to make sure they are getting similar glycemic control.

Although Lantus is approved to be given once a day, the duration of action of Lantus may vary for each individual with a duration of action as short as 11 hours. These patients may require dosing every 12 hours to suppress a rise in glucose levels. Clinical studies have not been conducted with 12-hour dosing.

NPH, on the other hand, may be given twice daily. Comparative studies in both type 1 and type 2 diabetes patients show that once-daily Lantus achieves equivalent HbA1c control to NPH insulin given once or twice daily.3 Lantus may have greater efficacy in decreasing fasting plasma glucose levels than NPH insulin, but results remain inconclusive.4,5 Patients who require twice-daily dosing with Lantus, may alternatively benefit with taking NPH twice a day, at half the cost. Lantus costs $5.50 per mL of insulin while Humulin N (NPH) costs $2.79 per mL. Using Lantus twice daily will double the costs compared to Humulin N, without an increased benefit. However, it’s important to remember that NPH insulin causes a peak in insulin whereas Lantus is “peakless.”

The lack of studies with Lantus and 12-hour dosing and inexperience with this type of dosing regimen suggest that it is too early to recommend twice-daily dosing over more established FDA approved regimens, such as NPH. NPH insulin twice daily offers a cost-effective alternative for patients requiring Lantus twice a day.

By providing a “peakless” insulin, Lantus makes an attempt to improve on some of the deficiencies in currently long acting insulins. It seems to produce a less variable effect on fasting glucose levels, suggesting that it has more predictable absorption than NPH insulin. This peakless action profile also causes less nighttime hypoglycemia and is conveniently dosed once a day. Lantus may be given at any time of the day, as long as the dose is given consistently the same time daily to prevent a rise in blood glucose levels. Remember to remind patients to check their blood glucose if they change their time of administration.

Lantus may benefit individual diabetic patients who have tried NPH insulin once or twice daily and need more consistent control in their HbA1c and therefore provides an alternative to NPH and Ultralente insulins. As with any insulin, the dose of Lantus must be individualized according to each patient’s needs. Remember that dose adjustments may be necessary when converting from once-daily or twice-daily intermediate- or long-acting insulins to Lantus. Patients who do not see adequate efficacy with once-daily dosing of Lantus, should use NPH twice daily at half the cost.

Lantus may also offer some disadvantages that should be communicated to patients. It can cause a greater incidence of pain at the injection site than NPH insulin. It also cannot be mixed with any other insulin or solution. Lantus is a clear solution, just like regular insulin and lispro insulin. Patients often differentiate their “long-acting” insulin by the fact that is it “cloudy.” With the addition of a “clear, long-acting” insulin, confusion on the patient’s part is inevitable. Patient counseling is vital to prevent medication administration errors. Also be careful to avoid errors by confusing “Lantus” with “Lente” or “lispro.” Suggest NPH insulin for patients who need BID dosing… it costs about half as much as Lantus. Advise patients who switch to morning Lantus dosing to monitor their blood glucose extra closely.

Product information for Lantus. Aventis Pharmaceuticals, Inc. Bridgewater, NJ 08807-2854. August 2002. Rosenstock J, Schwartz SL, Clark CM Jr, et al. Basal insulin therapy in type 2 diabetes: 28-week comparison of insulin glargine (HOE 901) and NPH insulin. Diabetes Care 2001 Apr;24(4):631-6.

Yki-Jarvinen H, Dressler A, Ziemen M. Less nocturnal hypoglycemia and better post-dinner glucose control with bedtime insulin glargine compared with bedtime NPH insulin during insulin combination therapy in type 2 diabetes. Diabetes Care 2000;23:1130-6.

Shaver K. New Drug: Lantus (insulin glargine [rDNA origin] injection). Therapeutic Research Center. Pharmacist’s Letter/Prescriber’s Letter 2001;17(5):170502

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