Practical Approaches for the Effective Use of Insulin Analogs: Integrating Evidence Into Practice

A CME symposium supported by an educational grant from Novo Nordisk

Malcom Nattrass, MB, PhD, FRCP
Robert Ratner, MD
Martin J Abrahamson, MD
Philip Raskin, MD

Reported by Joelle Escoffery, PhD

There are a variety of available approaches for patients with type 2 diabetes who require insulin therapy, including basal insulin, mixed insulin, and basal-bolus insulin, all of which can be accompanied by oral antihyperglycemic agents. Basal insulin is most appropriate for use among patients with elevated fasting plasma glucose (FPG) who desire only a single injection. Available options for basal insulin include insulin glargine, insulin detemir, or NPH insulin. Mixed insulin is a more effective strategy for targeting postprandial plasma glucose (PPG). Several premixed formulations are available, including 70/30 and 75/25, or self-mixing is also an option. Basal-bolus insulin gives better flexibility, especially for patients who have an erratic schedule. In addition to the basal insulin options mentioned previously, there are 3 rapid-acting insulin analogs available: insulin aspart, insulin lispro, and insulin glulisine.

Of the available basal insulins, glargine, detemir, and human NPH all have their onset of action at approximately 2-4 hours after injection. Glargine is peakless, and detemir is relatively peakless. NPH insulin peaks in 4-10 hours. In terms of duration, glargine lasts for approximately 24 hours, detemir can work for up to 24 hours, and NPH lasts from 12-20 hours. When comparing the available options for basal therapy, significantly more patients meet A1C targets without documented nocturnal hypoglycemia with insulin glargine compared with NPH (33% vs 27%, respectively). Similarly, more patients reach A1C goal without hypoglycemia when using insulin detemir compared with NPH insulin (26% vs 16%). Insulin detemir is also associated with less weight gain than NPH insulin. In a direct comparison of insulin detemir and insulin glargine, improvements in glycemic control were comparable. In terms of weight, there was no difference between twice-daily insulin detemir and insulin glargine. However, the mean difference in weight (insulin detemir-insulin glargine) was -1.71 (P<.001). The challenge of basal insulin therapy is that no postprandial coverage is given, so therapy to address PPG may be required.

Premixed insulin is another strategy that can be employed when oral agents are no longer sufficient to meet glycemic targets. Because  FPG is a larger contributor to A1C at higher glycemic levels, addressing FPG is a viable first strategy to reduce hyperglycemia. However, in patients who have significant ß-cell failure, basal insulin alone will not be sufficient to meet glycemic targets. As patients approach glycemic targets, PPG takes on greater importance. A comparison of premixed analog insulin (70/30) and pemixed human insulin showed that better control of PPG can be achieved with the use of premixed analog insulin. Premixed analog insulin was also associated with a lower incidence of major hypoglycemia compared with premixed human insulin. The INITIATE Trial examined the efficacy of glargine and oral agents compared with biphasic insulin analog insulin (70/30) and oral agents. Results showed that biphasic analog insulin is associated with significant improvements in A1C, more patients achieving glycemic targets, and an improved 8-point blood glucose profile. Similar results were seen when 75/25 insulin was tested in a crossover fashion. The 1-2-3 Study tested the efficacy of a 70/30 analog insulin given qd, bid, and tid. With each dose of insulin added, a greater percentage of patients met glycemic targets. When initiating insulin therapy, patients should be properly educated and counseled, and the benefits of insulin therapy should be communicated.

Because of the progressive nature of type 2 diabetes, glycemic targets may eventually not be met with basal insulin or premixed analog insulin, and intensification of insulin therapy will be required. Intensifying insulin therapy can be considered when A1C is above target with oral agents and insulin; hypoglycemia with use of premixed analog insulin that precludes further intensification; or the desire to more closely mimic a physiologic insulin regimen. Basal-bolus therapy using multiple daily injections (MDI) provides greater flexibility in terms of caloric intake and physical activity. When using basal-bolus therapy, use of insulin analogs was associated with a lower variability in self-measured FPG and a trend toward decreased risk of nocturnal hypoglycemia. Basal bolus therapy requires active patient involvement; patients should fully understand carbohydrate counting. Patients on basal-bolus therapy need to consider their current blood glucose level, their anticipated caloric intake and activity level, and their glycemic history under similar circumstances. For patients with type 2 diabetes who require basal-bolus therapy, insulin pump therapy is also an option, as it has been shown to achieve comparable glycemic improvements compared with MDI but with significantly higher levels of patient satisfaction.