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Continuous Subcutaneous Insulin Infusion Versus Multiple Daily Injections

The impact of baseline A1c

¹ Division of Endocrinology, University of Toronto, Toronto, Ontario, Canada
² Leadership Sinai Centre for Diabetes, Mount Sinai Hospital, Toronto, Ontario, Canada
³ Department of Medicine, University of Toronto, Toronto, Ontario, Canada
⁴ Department of Internal Medicine, Academic Medical Center, Amsterdam, the Netherlands
⁵ Service de Diabetologie, Hospital de Rangueil, CHU de Toulouse, Toulouse, France
⁶ Department of Endocrinology, Diabetes Center, VU University Medical Center, Amsterdam, the Netherlands

Address correspondence and reprint requests to Dr. Bernard Zinman, Leadership Sinai Centre for Diabetes, Mount Sinai Hospital, Lebovic Building, 5th Floor, Room L5-024, 600 University Ave., Toronto, Ontario, Canada M5G 1X5. E-mail: zinman{at}mshri.on.ca

OBJECTIVE—Rapid-acting insulin analogs (insulin lispro and insulin aspart) have emerged as the meal insulin of choice in both multiple daily insulin injection (MDII) therapy and continuous subcutaneous insulin infusion (CSII) for type 1 diabetes. Thus, a comparison of efficacy between CSII and MDII should be undertaken only in studies that used rapid-acting analogs for both intensive regimens.

RESEARCH DESIGN AND METHODS—We performed a pooled analysis of the randomized controlled trials that compared CSII and optimized MDII therapy using rapid-acting analogs in adults with type 1 diabetes.

RESULTS—The three studies that met inclusion criteria provided data on 139 patients, representing 596 patient-months for CSII and 529 patient-months for MDII. Mean age was 38.5 years, with duration of diabetes of 18.0 years. The studies differed significantly in mean baseline A1c (7.95, 8.20, and 9.27%). The pooled estimate of treatment effect comparing the percentage reduction in A1c by CSII with that by MDII (CSII – MDII) was 0.35% (95% CI –0.10 to 0.80, P = 0.08) using a random effect to account for heterogeneity between studies. Importantly, the interaction between baseline A1c and treatment modality emerged as an independent predictor of treatment effect (CSII – MDII) (P = 0.002). The relative benefit of CSII over MDII was found to increase with higher baseline A1c. A model derived from these data predicts that in a patient with a baseline A1c of 10%, CSII would reduce the A1c by an additional 0.65% compared with MDII. Conversely, there would be no A1c benefit of CSII compared with MDII if baseline A1c were 6.5%. There was no significant difference between CSII and MDII in the rate of hypoglycemic events.

CONCLUSIONS—When using rapid-acting insulin analogs in CSII and MDII regimens in adult patients with type 1 diabetes, insulin pump therapy is associated with better glycemic control, particularly in those individuals with higher baseline A1c. Thus, CSII emerges as an important modality for implementing intensive therapy and may be uniquely advantageous in patients with poor glycemic control.

Abbreviations: CSII, continuous subcutaneous insulin infusion • DCCT, Diabetes Control and Complications Trial • MDII, multiple daily insulin injection

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