Elsevier

Endocrine Practice

Volume 17, Issue 4, July–August 2011, Pages 563-567
Endocrine Practice

Original Article
Concomitant Oral Antihyperglycemic Agent Use and Associated Treatment Outcomes After Initiation of Insulin Therapy

https://doi.org/10.4158/EP10348.ORGet rights and content

ABSTRACT

Objective

To compare outcomes in patients with type 2 diabetes initiating insulin lispro mix 75/25 (75% insulin lispro protamine suspension and 25% lispro) or insulin glargine therapy, stratified by baseline oral antihyperglycemic agent (OHA) use.

Methods

We performed a post hoc analysis of 6-month data from the DURABLE clinical trial, which enrolled patients with hemoglobin A1c (A1C) levels > 7.0% treated with 2 or more OHAs (metformin, sulfonylurea, and thiazolidinedione), and randomly assigned them to treatment with twice-daily insulin lispro 75/25 or oncedaily glargine.

Results

In both insulin treatment groups, metformin/ thiazolidinedione-treated patients had significantly greater improvement in A1C levels (-2.19% to -2.36%), lower end point A1C values, and lower rates of occurrence of hypoglycemia in comparison with metformin/sulfonylurea-treated patients (all P < .05). Patients treated with sulfonylurea/thiazolidinedione or metformin/sulfonylurea/

thiazolidinedione did not differ significantly from metformin/sulfonylurea-treated patients in A1C change (-1.56% to -1.84%) or rates of occurrence of hypoglycemia.

Conclusion

In these post hoc analyses, patients with type 2 diabetes initiating premixed or basal insulin therapy and treated concomitantly with the OHA combination of metformin/thiazolidinedione at baseline demonstrated significantly greater A1C improvement with less hypoglycemia in comparison with patients treated with metformin/ sulfonylurea. (Endocr Pract. 2011;17:563-567)

Section snippets

INTRODUCTION

Type 2 diabetes mellitus is a progressive disorder, often requiring treatment intensification to achieve and maintain hemoglobin A1c (A1C) goals. Algorithms have been published to help guide clinicians regarding appropriate steps for treatment intensification (1,2). Recent controversy surrounding the thiazolidinedione class of oral antihyperglycemic agents (OHAs) has led to questions about the appropriate role for thiazolidinedione therapy within type 2 diabetes treatment algorithms (2, 3, 4, 5

RESEARCH DESIGN AND METHODS

Six-month data from the DURABLE clinical trial (6) were used in these analyses. The DURABLE trial was a 30-month, multinational, open-label, 2-arm, parallel study conducted in accordance with the Declaration of Helsinki and approved by site institutional review boards (6). All patients provided written informed consent. Patients were 30 to 80 years of age with type 2 diabetes and A1C levels > 7.0% and were treated with a combination of 2 or more OHAs, including metformin, sulfonylurea, and a

STATISTICAL ANALYSES

We performed statistical analyses on the intent-totreat population of 1,961 patients with at least one postbaseline A1C assessment using the last observation carried forward method. All analyses were conducted within each insulin treatment group (insulin lispro mix 75/25 or insulin glargine). Continuous baseline characteristics were compared between the largest cohort (metformin/sulfonylurea) and other OHA groups by using analysis of variance. End point A1C, A1C change, mean plasma glucose

RESULTS

The largest OHA subgroup was the metformin/sulfonylurea group, accounting for approximately 65% of patients. Baseline characteristics in the 4 OHA groups were similar, except that patients in the metformin/thiazolidinedione groups were younger and had higher BMI in comparison with the metformin/sulfonylurea groups (Table 1).

The baseline A1C level did not differ significantly between metformin/thiazolidinedione and metformin/sulfonylurea groups. Within each insulin cohort, after 24 weeks, the

DISCUSSION

In comparison with the metformin/sulfonylurea group, patients in the metformin/thiazolidinedione group who initiated insulin treatment had significantly lower end point A1C and greater A1C improvement with less hypoglycemia, even though baseline A1C levels were similar in these 2 subgroups for each insulin treatment. After adjustment for factors that might affect glycemia, the metformin/ thiazolidinedione group continued to demonstrate greater A1C improvement after initiation of insulin

CONCLUSION

Despite the aforementioned limitation, our results suggest that metformin/thiazolidinedione treatment is associated with better short-term glycemic outcomes in patients with type 2 diabetes initiating insulin therapy and that OHA combination therapies including sulfonylurea are associated with worse glycemic outcomes. Although thiazolidinedione therapy is often discontinued when insulin treatment is initiated (2), this post hoc analysis suggests that continuing thiazolidinedione in conjunction

DISCLOSURE

Dr. Kathleen M. Dungan has performed consulting for AstraZeneca and Cangene Corporation and has received research support from Novo Nordisk Inc. Dr. John B. Buse is a consultant or investigator under contract with the University of North Carolina with multiple companies, which provide no direct financial benefit to him. They include the following: Amylin Pharmaceuticals, Bayhill Therapeutics, BD Research Laboratories, Bristol- Myers Squibb, Hoffmann-La Roche Inc., Intuity Medical, Johnson &

ACKNOWLEDGMENT

The DURABLE study was funded by Lilly USA, LLC.

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