Clinical Geriatrics

Optimizing Diabetes Management With Insulin Analogs Levemir and NovoLog

Diabetes, particularly the type 2 variant, is becoming more prevalent, increasing the burden on clinicians. Individuals with diabetes are more likely to require extended hospital stays, develop significant neuropathic pain, and experience depression. Effective management of diabetes in older patients requires overcoming several barriers, including comorbid diseases, preexisting complications of poorly managed diabetes, an elevated risk of hypoglycemia, and greater insulin resistance. As a result, many patients have difficulty achieving a glycated hemoglobin (A_1c) level of <7%, which is the level the American Diabetes Association (ADA) considers evidence of optimal glucose control, said Brian Tulloch, MD, Clinical Endocrinologist and Associate Professor,
Diagnostic Clinic of Houston, TX. In a product theater sponsored by Novo Nordisk at the 2011 ASCP annual meeting, Tulloch discussed the benefits of two insulin analog therapies—Levemir (insulin detemer) and NovoLog (insulin aspart)—and addressed current standards for managing and treating diabetes.

Levemir is administered as a subcutaneous injection once or twice daily in diabetic patients who require basal insulin. Tulloch said the effectiveness of once-daily Levemir at controlling blood glucose was demonstrated in TITRATE, a 20-week, open-label, multicenter trial. TITRATE’s researchers randomized 244 insulin-naïve patients taking an oral antidiabetic drug (OAD) for type 2 diabetes to one of two groups. One group was instructed to self-titrate Levemir to achieve a target fasting glucose level of 70 mg/dL to 90 mg/dL, as measured with a fasting plasma glucose (FPG) test, and the target for the other group was set at 80 mg/dL to 110 mg/dL. Every 3 days, patients adjusted their insulin dose as needed to achieve the target, with the increase or decrease in insulin based on the mean FPG values from the prior 3 days. By the study’s conclusion, 64.3% of patients in the 70 md/dL to 90 mg/dL target group and 54.5% of patients in the 80 mg/dL to 110 mg/dL group had achieved A_1c levels <7%. The mean A_1c level for the groups combined was 6.9%. From baseline, A_1c levels declined a mean of 1.2% for patients assigned to the group with the lower FPG target versus 0.9% for patients assigned to the group with the higher FPG target.

Tulloch explained that human insulin comprises 51 amino acids; 21 of these constitute the A polypeptide chain and the remaining 30 constitute the B polypeptide chain. A disulfide bond links the A chain to the B chain. Levemir was engineered to attach a fatty acid chain to amino acid B29. He said the fatty acid chain enhances Levemir’s ability to bind to albumin. Studies comparing Levemir with insulin glargine have observed a similar 24-hour effect on blood glucose with both agents but more consistent absorption and action and significantly less weight gain with Levemir. Unlike insulin glargine, Levemir is soluble at neutral pH.

The second analog discussed, NovoLog, is absorbed faster than human insulin and thus has a faster onset and shorter duration of action. Tulloch said NovoLog is typically injected 5 to 10 minutes before meals. In the 48-week randomized, multinational STEPwise trial, researchers compared two stepwise schedules for gradually increasing the NovoLog dose in adults (N=296) with type 2 diabetes that was poorly controlled despite the use of basal insulin and OADs. In the “SimpleSTEP” group, an initial injection of NovoLog was given with the largest meal, blood glucose was measured prior to subsequent meals, and additional doses were based on those results. Individuals assigned to the “ExtraSTEP” group took the initial NovoLog dose before the meal associated with the greatest increases in blood sugar as measured before and after the meal, with the primary NovoLog dose adjusted according to the level of glucose control achieved. Nearly one-third (31%) of patients in the SimpleSTEP group achieved the A_1c goal of <7%. Tulloch said another study—the 3-year 4-T study—involving 708 insulin-naïve patients with type 2 diabetes found that a majority achieved and maintained the target A_1c level when using NovoLog as part of a basal-bolus therapy.

A NovoLog 70/30 mix (70% insulin aspart protamine suspension, 30% insulin aspart injection) is also available. The mix has a faster onset than human insulin premix 70/30. The open-label, nonrandomized, observational IMPROVE study was used to demonstrate the effectiveness of this
NovoLog formulation.

During the presentation, Tulloch also demonstrated the convenience of the NovoLog FlexPen. He said NovoLog remains stable in the FlexPen, in the 3-mL PenFill cartridges, and in 10-mL vials for up to 28 days when stored at room temperature or until its expiration date if refrigerated.—David Despain

This product theater was sponsored by Novo Nordisk.