In a recent editorial (1), Davidson commented on two studies (2,3) in which insulin initiation using a basal insulin analog was compared with either a human insulin premix or an analog insulin premix. These articles have prompted further correspondence concerning the design and results of these studies (4,5).
Mikhail and Cope (4) and Janka (5) commented that the greater HbA1c reduction observed in patients taking biphasic insulin aspart 70/30 (BIAsp 70/30), as compared with insulin glargine, may be attributed to a greater dose of BIAsp 70/30. They suggested that glargine was not titrated to the fullest extent in the INITIATE study. However, the fasting blood glucose values achieved with titration of the evening dose of glargine were the same in the INITIATE, Treat-to-Target (6), zand Janka et al. (2) studies (from 117 to 115 mg/dl). These blood glucose values, as well as those for the BIAsp 70/30 in INITIATE, were slightly above the targeted fasting glucose values and suggest a reluctance by clinicians to titrate insulin to the fullest extent. It is not surprising that there was a greater BIAsp 70/30 dose, as there was a second insulin injection to titrate. The administration of twice-daily BIAsp 70/30 during INITIATE provided coverage of postprandial glycemia during breakfast and the evening meal, often the biggest meals of the day. With the growing acceptance of the importance of postprandial glycemia on overall glycemic control, a premix analog insulin has the advantage over a single basal injection of targeting and reducing postprandial glucose excursions.
With a greater insulin dose, more hypoglycemia and weight gain might be expected. However, no subjects in the BIAsp 70/30 group had a major hypoglycemic episode, nor did any withdraw from the study because of hypoglycemia. Therefore, hypoglycemia was not an impediment to the pursuit of glycemic control for the BIAsp 70/30 group, which had a greater percentage of patients reach the target HbA1c of <7%, compared with the glargine group (66 vs. 40%, respectively).
As aptly stated in the Davidson editorial, the most important factor in initiating insulin therapy is to “intensify the approach until targets are achieved and then to maintain them.” With the success rate observed in the INITIATE study, the premixed formulation of BIAsp 70/30 clearly is a viable option for initiating insulin therapy and for achieving glycemic targets in a majority of insulin-naïve patients with type 2 diabetes.
