Achieving glycemic goal with initial versus sequential combination therapy using metformin and pioglitazone in type 2 diabetes mellitus

Abstract

Objective:

To compare glycemic goal achievement (HbA_1c < 7%) in type 2 diabetes patients receiving initial metformin plus pioglitazone combination therapy and initial metformin monotherapy augmented with pioglitazone in a cohort follow-up study.

Research design and methods:

Adult patients were identified from the Ingenix Impact database (01/01/99–03/31/07). Qualified patients had a baseline HbA_1c ≥ 7%; a second laboratory value within 9 months; no other anti-diabetic prescriptions 6 months before or 30 days after treatment initiation; and continuous enrollment during baseline. The index date was the date on which the second medication was initiated. Goal achievement was compared independently at 6, 12 and 18 months using a chi-square test. Logistic regression was used to control for baseline differences. Last observation carried forward was used to impute missing HbA_1c values. Sub-group analysis was conducted on patients with baseline HbA_1c values between 7% and 9%, and >9%.

Main outcome measures:

The proportion of patients achieving glycemic goal at each specified time point.

Results:

A total of 179 patients received initial combination therapy and 347 patients received sequential therapy. A greater proportion of initial combination patients achieved the glycemic goal compared to sequential patients at months 6, 12 and 18 (66.5 vs. 49.6%; 65.9 vs. 48.1%; 65.9 vs. 48.4%, respectively; p < 0.001 for all). Logistic regression confirmed these findings (odds ratios [OR]: 3.18–3.31). Sub-group analysis showed a more pronounced advantage for aggressive initial combination treatment among patients with HbA_1c > 9% (OR: 5.39–6.04) than among patients with HbA_1c between 7% and 9% (OR: 2.28–2.79).

Conclusions:

Initial combination therapy patients are more likely to achieve glycemic control than sequential therapy patients, especially for patients with baseline HbA_1c > 9%. This study is limited by the relatively small sample size and the frequency of HbA_1c reporting. Future research could examine goal achievement using a larger sample and more complete laboratory data to confirm these findings.

Key words::

• Combination therapy
• Diabetes mellitus
• Metformin
• Pioglitazone

Transparency

Declaration of funding

This study was supported by Takeda Pharmaceuticals International, Inc., Deerfield, IL, USA.

Declaration of financial/other relationships

B.J.P., M.B. and T.M. have disclosed that they are employees of Takeda. E.Q.W., K.S.C., A.P.Y. and M.E.M. have disclosed that they are employees of Analysis Group, Inc. which received funding from Takeda for consulting. B.J.P., M.B., T.M., E.Q.W., A.P.Y. and K.S.C. contributed to the discussion and reviewed/edited the manuscript. M.E.M. researched the data, contributed to the discussion and wrote and reviewed/edited the manuscript.

Acknowledgments

The authors thank Dr Robert R. Henry, Chief, VA Endocrinology & Metabolism and Professor of Medicine at the University of California, San Diego School of Medicine, San Diego, CA, USA for his invaluable assistance in reviewing the data described in this manuscript.

Data in this paper were presented in abstract form at the American Diabetes Association Annual Meeting June 6–10, 2008 in San Francisco, CA, USA and as a poster at the European Association for the Study of Diabetes September 7–11, 2008 in Rome, Italy.