Should Insulin Glargine Be Dosed Once or Twice Daily?

Jenny A. Van Amburgh, PharmD, CDE

Disclosures

December 02, 2008

Question

Insulin glargine (Lantus®, sanofi-aventis) claims to have a 24-hour duration of action. Is there any advantage to using it twice daily? If so, what patient population might benefit from twice-daily dosing?

Response from Jenny A. Van Amburgh, PharmD, CDE

Associate Clinical Professor, School of Pharmacy, Northeastern University, Boston, Massachusetts; Director of the Clinical Pharmacy Team and Residency Director, Harbor Health Services, Inc., Boston, Massachusetts

Since its approval in April of 2000, insulin glargine has been used successfully in the treatment of sustained hyperglycemia in patients with type 1 or type 2 diabetes mellitus.[1] Long-acting insulin formulations such as glargine offer patients a steady, "peakless" 24-hour release of insulin for blood glucose control, in a convenient once-daily dosing schedule. Insulin glargine exerts its therapeutic effects by mimicking the basal secretion of pancreatic insulin to provide around-the-clock coverage for patients with elevated fasting plasma glucose levels. As with other diabetes treatments, the goal of insulin therapy is to prevent both microvascular (eg, retinopathy, neuropathy, nephropathy) and macrovascular (eg, stroke, myocardial infarction) outcomes.

Although insulin glargine is US Food and Drug Administration-approved for once-daily dosing, the actual duration of action ranges from 10.8 to more than 24 hours in some patients.[1,2] This fairly wide range suggests that a second dose may be necessary to achieve optimal glycemic control, although this is considered off-label use.[3,4]

To further investigate the variability in duration of action, an 8-week, 2-way crossover study was conducted in 20 patients with type 1 diabetes who used insulin aspart at mealtimes.[4] The aim was to determine if a twice-daily regimen of insulin glargine (given at breakfast and dinner) produced greater glycemic control than a once-daily regimen (given at dinner). Patients were instructed to self-monitor blood glucose (SMBG) on a daily basis. After 4 weeks, subjects were crossed over into the opposing treatment arm. At the end of the study period, the mean 24-hour SMBG concentration was significantly lower with twice-daily insulin glargine (P = .031), whereas once-daily insulin glargine resulted in higher glucose concentrations through the afternoon.[4]

A case report illustrates the utility of a second insulin glargine injection in some patients. A 53-year-old man with a 16-year history of type 1 diabetes was hospitalized for treatment of compensated ketoacidosis, and was placed on an insulin drip.[3] Prior to admission, he was using a daily 4-injection regimen of lispro and ultralente insulin. On day 5 of his hospitalization, the patient was started on enteral feedings. At 9 PM on day 6, he was given 30 units of insulin glargine and his insulin drip was tapered over the next several hours and then discontinued. From days 7 to 12 (period 1), the patient received insulin glargine as a single evening dose. From days 13 to 18 (period 2), insulin glargine was divided into 2 doses, administered at 9 AM and again 12 hours later. The patient's mean blood glucose level was significantly higher at 10 PM in treatment period 1 than in period 2. This suggests that the slow onset of action of insulin glargine, in conjunction with a constant intake of carbohydrates, results in breakthrough hyperglycemia.

This case study demonstrates that in certain patients with type 1 diabetes, a once-daily injection of insulin glargine may be insufficient to prevent breakthrough hyperglycemia.[3] In type 2 diabetic patients with decreased insulin secretion and insulin resistance, a second injection of insulin glargine might be necessary. Furthermore, patients in whom insulin glargine absorption is slowed, either because of excessive carbohydrate intake or the formation of depots caused by large doses of insulin glargine, a twice-daily injection may be warranted.

Further investigations are needed to clarify the role of twice-daily insulin glargine in patients with type 1 and type 2 diabetes. For now, it is wise to recommend once-daily insulin glargine. However, if a second dose is needed for optimal glycemic control, consider switching to twice-daily neutral protamine Hagedorn (NPH) insulin. Although hypoglycemia is a concern, NPH has proven comparable to glargine[5,6] and has the added benefits of being over-the-counter and less expensive.

The author wishes to acknowledge the assistance of Stefanie C. Nigro, PharmD, Pharmacy Practice Resident at Northeastern University School of Pharmacy and Harbor Health Services, Boston, Massachusetts.

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