This study suggests that the optimization of basal NPH insulin replacement with insulin lispro by CSII or an MDI-based regimen of once-daily insulin glargine plus insulin lispro results in similar improvement of glycemic control in people with type 1 diabetes who are naïve to either treatment regimen. Both regimens achieved similar improvements in A1C, self-monitored plasma glucose, and hypoglycemia.
The best estimate of difference between the regimens is −0.1% A1C, but study power implies that the actual difference could be between a CSII advantage of 0.5% and an MDI advantage of 0.3%. The present study is limited by the number of participants and a duration of 6 months but has the advantage of being the first prospective, multicenter study demonstrating noninferiority of the insulin glargine–based regimen versus CSII. Another possible limitation of the present study is that the MiniMed 508 pump, rather than the recent Paradigm 522 or 722 pump with the bolus wizard, was used. The latter pumps might be helpful to estimate bolus doses by calculating the insulin-to-carbohydrate ratio, insulin sensitivity factor, target blood glucose, and insulin on board (putative length of action of insulin bolus). However, randomized, controlled trials are required in the adult population to prove these benefits. In addition, an expert system might prove useful in MDI as well.
The mean end-of-study A1C levels for both regimens were close to American Diabetes Association targets and were similar to those in the intensive arm of the DCCT trial (1
). Although the baseline levels were higher on NPH insulin regimens, the present study did not examine the use of NPH insulin and the fall from baseline may have been a study effect, though consistent with previous comparisons of CSII and insulin glargine–based MDI with NPH insulin–based MDI (16
). However, NPH insulin regimens can be optimized by multiple NPH insulin injections (20
As expected, intensification of blood glucose control and careful recording resulted in increased reported rates of nonsevere hypoglycemia with no difference between regimens. Severe hypoglycemia was rare, but the inclusion criteria excluded people prone to this problem. Others have noted that the DCCT-derived conclusion of an increase in severe hypoglycemia is not necessarily reproduced when intensive insulin therapy is based on insulin analogs (9
Although blood glucose control with CSII and insulin glargine–based MDI was similar by other measures, plasma glucose predinner was higher with the latter regimen. This elevation in blood glucose in the late afternoon hours on an insulin glargine–based MDI regimen has been noted previously (21
). In some people with type 1 diabetes, the duration of action of insulin glargine appears to be <24 h. However, continued food absorption beyond the duration of action of the lunchtime insulin may be another cause of predinner hyperglycemia, as the phenomenon is attenuated when lunch is skipped (21
). With CSII it is possible that this was counteracted by higher basal rates in the afternoon, but these data were not collected. With insulin glargine, an additional bolus of rapid-acting analog 2–3 h after lunch can be given (21
); this was not part of the protocol of the present study. Interestingly, the theoretical advantage of multiple basal rates with CSII did not translate into lower basal plasma glucose levels at other times of day (C
). Furthermore, this study confirms that the magnitude of any “dawn phenomenon” is modest when basal insulin is optimally replaced with either CSII or an insulin glargine regimen (22
In the present study, glucose variability with CSII and insulin glargine–based MDI was not different. A previous study (23
) that compared people on long-term CSII with those switched to insulin glargine–based MDI found a small advantage of CSII in glucose variability, despite no difference in overall glycemic control. However, the importance of variability of blood glucose when A1C, hypoglycemia, and plasma glucose profile are identical is doubtful. Other data support the importance of glucose variability for vascular complications in diabetes, but clinical studies have yet to confirm this (24
That the costs of CSII are higher than those of MDI is perhaps obvious given the costs of pumps and infusion sets. There will also be a small saving in any market where insulin glargine is more expensive than insulin lispro. In economic terms, with similar efficacy but higher costs, CSII is “dominated” by MDI. The National Institute for Health and Clinical Excellence (U.K.) calculated a higher cost in the order of €1,392 to €1,772 per year, compatible with our results (25
The present study adds to previous observations (14
) of the noninferiority of insulin glargine–based MDI versus CSII in different study designs. A similar conclusion to ours was recently reported (23
) in a study in which people with type 1 diabetes were transferred from long-term CSII initiated primarily in the NPH insulin era to insulin glargine–based MDI. Thus, it is likely that the majority of people with type 1 diabetes who started CSII in the NPH insulin era did so due to the poor performance of basal NPH insulin. Similarly, it is likely that the majority of these people might today switch to MDI based on insulin glargine with no deterioration of blood glucose control (23
While the conclusions of the present study establish noninferiority of insulin glargine–based MDI against CSII in unselected (except for study purposes) people with type 1 diabetes, they cannot be applied to “selected” people with type 1 diabetes who may have special indications to CSII, such as long duration of disease with low insulin requirements or hypoglycemia unawareness with frequent, severe hypoglycemia on long-acting insulin analog–based MDI (6
). Additional studies are required in these groups of selected people with type 1 diabetes to establish the possible equivalence or otherwise of insulin glargine–based MDI against CSII with regard to glycemic control and the incidence and awareness of hypoglycemia.