New Data on Glargine and CSII?
An earlier "Ask the Expert" question this year dealt with insulin pumps. At the time, there were significant advantages to using insulin glargine and insulin pumps for the treatment of diabetes, but there were no head-to-head studies. Are there any new data?
Response from M. James Lenhard, MD
Medical Director, Weight Management Program, Preventative Medicine and Rehabilitation Institute and Chief, Section of Endocrinology, Christiana Care Health Systems, Wilmington, Delaware.
Continuous subcutaneous insulin infusion (CSII), or insulin pump therapy, represents an increasingly popular method of treating diabetes. Several studies were presented at the 63rd Scientific Sessions of the American Diabetes Association that examined CSII compared with glargine.
Glargine is a long-acting basal insulin, with little or no peak over its 24-hour profile. When used with rapid-acting insulin analogs such as aspart or lispro, it has been called the "poor man's pump" because the basal and bolus regimen is similar to that obtained with an insulin pump. A randomized, prospective comparison between CSII and glargine in children was conducted at Yale University. Twenty-six children (39% male, 79% white) with a mean age of 12.7 ± 2.7 years completed the 16-week study. The study is ongoing, and after 16 weeks the subjects are allowed to choose the therapy they desire. The children who were randomized to multiple daily injections (MDI) with glargine and aspart had no significant change in their hemoglobin A1C (HbA1c), with values declining minimally from 8.4% to 8.1%. The children on CSII with aspart had a significant decline, from 8.1% to 7.2%. There were 4 severe hypoglycemic events in the group treated with MDI, and 2 severe events in the group treated with CSII. In addition, subjects randomized to the group with CSII were able to decrease their total daily dose of insulin, while the subjects in the MDI group had no change. The study authors concluded that CSII was more effective at controlling type 1 diabetes in children than was MDI.
A retrospective chart review of 103 patients with type 1 diabetes compared CSII (58 patients) with MDI (45 patients) consisting of glargine plus a rapid-acting insulin analog. This study used a longer duration of treatment than the Yale study described above, with 16 months of treatment for the CSII group and 11.6 months for the MDI group. The authors found no difference in HbA1c levels between the 2 groups (6.79% vs 6.84%), nor was there a difference in severe hypoglycemic events.
A third study looked at patients who wanted to take a break from CSII and go on a pump holiday. Thirty patients with CSII-treated type 1 diabetes were randomized to either 4 months of continuing CSII or MDI with glargine and an analog. There was no significant change in the HbA1c levels in either group, nor was there a change in the incidence of hypoglycemia.
Also presented was a multicenter, open-label, randomized crossover study of adults with type 1 diabetes. This study involved 100 subjects with CSII-treated diabetes. Subjects were randomized to either continuing CSII or MDI with glargine and aspart. After 5 weeks the patients were switched to the alternative therapy for 5 additional weeks. During the last week of each treatment period, subjects wore a continuous glucose monitoring system (CGMS; Medtronic MiniMed) for 2-3 days. Glycemic control was superior with CSII as measured by fructosamine (343 vs 355 micromol/L for CSII and MDI, respectively) or by area under the curve glucose from the CGMS. There was no change in hypoglycemia.
These 4 studies are interesting but probably are not the final chapter in the comparison between CSII and MDI. They confirm some of the things that we already know about CSII. CSII is usually at least as effective as MDI in both achieving glycemic control and preventing hypoglycemia, and may be superior. The skill, training, and patience of the healthcare team providing the treatment directly affect success with CSII as well as MDI. The proper selection of the patients who use CSII plays a significant role in the successful outcome. It is possible that studies that fail to show an improvement in outcome from using CSII suffer from excessively talented healthcare providers that are capable of achieving excellent outcomes with MDI.
In addition, these studies raise some additional questions: What is the optimal length of time to compare outcomes between CSII and MDI? Do outcomes differ between children and adults? How much of the observed differences can be explained by patient preference and motivation? Hopefully the answers to these questions and others will be addressed with ongoing research.