Initiation of Insulin in Patients With Type 2 Diabetes Failing Oral Therapy: Response to Raskin et al. and Mikhail and Cope

Our previous publication regarding the initiation of insulin therapy in patients with type 2 diabetes failing oral therapy (1) and the recent study by Raskin et al. (2) has raised interesting discussion (3,4). Raskin et al. reported that glycemic control was better in patients treated with BIAsp 70/30 plus oral antidiabetic agents (OADs) than in those receiving insulin glargine plus OADs (mean end point HbA_1c 6.91 vs. 7.41%). In contrast, we demonstrated that glycemic control was better in patients treated with insulin glargine plus OADs compared with 70/30 insulin alone (mean end point HbA_1c 7.15 vs. 7.49%). Major discrepancies between the Raskin et al. study and our study exist, including considerably poorer metabolic control at study baseline in the Raskin et al. study (HbA_1c 9.8 vs. 8.8%), the use of different OADs, a markedly higher insulin dose at study end (78.5 IU BIAsp 70/30 vs. 28.2 IU in our insulin glargine plus OAD study group), and a dramatic weight gain in the BIAsp 70/30 group (5.4 kg vs. only 1.4 kg in our insulin glargine plus OAD group).

On the surface, it might appear that according to Raskin et al., premix insulin plus OADs were more effective than insulin glargine plus OADs. However, this does not take into account other factors that influence treatment management, including insulin dose, number of daily injections, complexity when monitoring blood glucose, incidence of hypoglycemia, weight gain, and quality of life. Indeed, in both studies, insulin dose and the incidence of hypoglycemia were significantly greater with premix insulin versus insulin glargine. Further analysis has indicated that although the method for identifying hypoglycemia was very different between the two studies, the nearly fivefold higher incidence of hypoglycemia observed in the premixed arm is of major clinical relevance. Aside from the debilitating effect of hypoglycemia on the patient and carers, hypoglycemia has important health economic implications. Additionally, whereas insulin glargine is injected only once daily, premix insulin requires twice-daily administration and blood glucose monitoring two to four times daily, a likely barrier to achieving treatment success, particularly in clinical practice with insulin-naïve patients being initiated to insulin therapy. Furthermore, one might question whether the results obtained by Raskin et al. reflect the true potential of insulin glargine; given the low risk of hypoglycemia observed with insulin glargine, more aggressive titration of this insulin in their study may have achieved a greater decrease in HbA_1c.

We believe that one injection of insulin glargine in combination with two OADs is a simple, safe, and effective treatment option for patients with type 2 diabetes with moderately unstable blood glucose control.