Elsevier

Endocrine Practice

Volume 17, Issue 3, May–June 2011, Pages 395-403
Endocrine Practice

Original Article
A Stepwise Approach to Insulin Therapy in Patients with Type 2 Diabetes Mellitus and Basal Insulin Treatment Failure

https://doi.org/10.4158/EP10323.ORGet rights and content

ABSTRACT

Objective

To determine whether 1 or 2 preprandial injections before the meals of greatest glycemic impact can be as effective as 3 preprandial injections in patients with type 2 diabetes mellitus and basal insulin treatment failure.

Methods

This was an open-label, parallel-group, 1:1:1 randomized study of adults with type 2 diabetes mellitus on oral antidiabetic drugs with glycated hemoglobin (A1C) levels of 8.0% or greater. After a 14week run-in with insulin glargine, patients with an A1C level greater than 7.0% were randomly assigned to 1, 2, or 3 time(s) daily insulin glulisine for 24 weeks. Changes in A1C from randomization to study end; percentage of patients achieving an A1C level less than 7.0%; changes in A1C, fasting glucose concentrations, and weight at individual study points; and safety (adverse events and hypoglycemia) were assessed throughout the study.

Results

Three hundred forty-three of 631 patients (54%) completing the run-in phase with insulin glargine were randomly assigned to treatment arms. During the randomization phase, A1C reductions with insulin glulisine once or twice daily were noninferior to insulin glulisine 3 times daily (confidence intervals: -0.39 to 0.36 and -0.30 to 0.43; P > .5 for both). However, more patients met the target A1C with 3 preprandial injections (46 [46%]) than with 2 injections (34 [33%]) or 1 injection (30 [30%]). Severe hypoglycemia occurred in twice as many patients receiving 3 preprandial injections (16%) compared with those receiving 2 injections (8%) and 1 injection (7%), but these differences did not reach significance.

Conclusion

This study provides evidence that initiation of prandial insulin in a simplified stepwise approach is an effective alternative to the current routine 3 preprandial injection basal-bolus approach. (Endocr Pract. 2011;17:395-403)

Section snippets

INTRODUCTION

The American Diabetes Association (ADA) recommends a glycated hemoglobin A1c (A1C) target less than 7.0% (1), which, unfortunately, fewer than 60% of diabetic patients achieve (2, 3). Owing to the progressive nature of type 2 diabetes mellitus, insulin therapy is often required to achieve glycemic control (4, 5). When lifestyle modifications and treatment with metformin with or without other oral antidiabetic drugs (OADs) have failed to achieve normoglycemia, timely initiation of singledose

RESULTS

Patient Disposition, Demographics, and Characteristics at Randomization

A total of 1232 patients were screened, of which 785 (64%) participated in the 14-week run-in period and were treated with insulin glargine (Fig. 2). Among these, 288 achieved an A1C concentration of 7.0% or less at the end of the run-in period and were not eligible for randomization. A total of 154 of 785 patients (20%) withdrew during the run-in period; withdrawal reasons are listed in the Figure 2 legend. The remaining

Glycemic Control

Treatment with insulin glargine during the 14-week run-in phase reduced mean A1C levels from greater than 10.0% at screening to ~ 8.0%, with 37% of those starting the run-in and 46% of those completing the run-in achieving the target A1C level of 7.0% or less. The final glargine dosage was the same (0.55 units/kg) in those who achieved the target A1C level at the end of the run-in period and in those who did not. At study endpoint (week 24), participants in the 1 ×, 2 ×, and 3 × groups were taking

DISCUSSION

Nearly half of the patients who finished the run-in phase achieved the A1C target level of 7.0% or less after 14 weeks of treatment with insulin glargine. In patients not achieving goal A1C levels with basal insulin, intensification of insulin therapy by adding prandial insulin is a logical next step to minimize postprandial glycemic excursions (6). After the 14-week run-in period, during which insulin glargine was actively titrated to achieve fasting goals, insulin glulisine was added for

CONCLUSION

The clinical evidence in support of initiating prandial insulin via progressive increases in the number of preprandial injections as necessary, as an alternative treatment algorithm, may simplify intensification of insulin therapy, improve the willingness of physicians and patients to aggressively manage diabetes, and significantly improve glycemic control for patients with type 2 diabetes. Further studies are needed to prospectively evaluate the proportion of patients requiring 1, 2, or 3

DISCLOSURE

The authors have no multiplicity of interest to disclose.

ACKNOWLEDGMENT

Clinical Trial Registration: NCT00135083. Study and editorial support funded by sanofi-aventis U.S.

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