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Lee, Lee, Baik, Choi, Park, Song, Lee, Cha, Ahn, Lee, Chung, Nam, Baek, Kim, Rhim, and Son: Comparison of the Efficacy and Safety of Glimepiride/Metformin Fixed Combination Versus Free Combination in Patients with Type 2 Diabetes: Multicenter, Randomized, Controlled Trial
Original Article
The Journal of Korean Diabetes Association

The Journal of Korean Diabetes Association 2006; 30(6): 466-475.

Published online: 30 November 2006

DOI: https://doi.org/10.4093/jkda.2006.30.6.466

Comparison of the Efficacy and Safety of Glimepiride/Metformin Fixed Combination Versus Free Combination in Patients with Type 2 Diabetes: Multicenter, Randomized, Controlled Trial

Seung-Hwan Lee, In-Kyu Lee1, Sei-Hyun Baik2, Dong-Seop Choi3, Kyong-Soo Park4, Ki-Ho Song5, Kwan-Woo Lee6, Bong-Soo Cha7, Chul-Woo Ahn8, Hyoung-Woo Lee9, Choon-Hee Chung10, Moon-Suk Nam11, Hong-Sun Baek12, Yong-Ki Kim13, Hyo-Young Rhim14, Ho-Young Son

Kangnam St. Mary's hospital, The Catholic University of Korea, Korea.

1Keimyung University Medical Center, Korea.

2Korea University Guro Hospital, Korea.

3Korea University Anam Hospital, Korea.

4Seoul National University Hospital, Korea.

5St. Vincent Hospital, The Catholic University of Korea, Korea.

6Ajou University Hospital, Korea.

7Severance Hospital, Yonsei University, Korea.

8Yongdong Severance Hospital, Yonsei University, Korea.

9Yeongnam University Medical Center, Korea.

10Wonju Christian Hospital, Korea.

11Inha Universtiy Hospital, Korea.

12Chonbuk National University Hospital, Korea.

13Pusan National Universtiy Hospital, Korea.

14Handok Pharmaceuticals Co., LTD., Korea.

Received 29 May 2006       Accepted 20 November 2006

Copyright © 2006 Korean Diabetes Association

Abstract

Background

Failure to manage diabetes mellitus receiving monotherapy increases as the duration of the disease is protracted, and in many cases it becomes inevitable to introduce combined therapies. However, compliance of the patients tends to decrease. We conducted a clinical study to compare the efficacy and safety of preconstituted and fixed combination therapy of glimepiride plus metformin to those of free combination therapy.

Methods

Two hundred and thirteen patients with type 2 diabetes who had been diagnosed at least six months ago were randomly assigned either to a fixed group or a free group. The initial dosage was chosen according to the previous treatment history and then adjusted every two weeks following a predefined titration algorithm to meet the target mean fasting glucose levels (140 mg/dL). The medications were given for 16 weeks. The primary endpoint was the change in HbA1c level from baseline to week 16. Various parameters were checked as secondary outcome measures and safety criteria.

Results

HbA1c level of the fixed group and the free group decreased by 1.09% and 1.08%, respectively. The 95% CI of the changes' difference between the two groups (-0.21%, +0.19%) was within the predefined equivalence interval (-0.5%, +0.5%). Secondary outcome measures (the changes of fasting and postprandial plasma glucose level, response rate and compliance) and safety criteria (frequency of hypoglycemia and adverse reactions) were similar between the two groups.

Conclusion

Fixed combination of glimepiride/metformin is as effective and safe therapy as free combination in type 2 diabetes patients.

Keywords: Combination, Glimepiride, Metformin, Type 2 diabetes

Figures and Tables

Fig. 1
Flow of patients through the study.
ITT, intent-to-treat; PP, per protocol.
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Table 1
Decision of the Initial Dose
jkda-30-466-i001

1st step, Glimepiride 1 mg/ Metformin 250 mg bid; 2nd step, Glimepiride 2 mg/ Metformin 500 mg before breakfast & Glimepiride 1 mg/ Metformin 250 mg before dinner; 3rd step, Glimepiride 2 mg/ Metformin 500 mg bid.

*Glibenclamide 7.5 mg or gliclazide 120 mg.

†Initial dose according to the step.

Table 2
Patient Characteristics at Study Entry
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Table 3A
Initial dose
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Table 3B
Daily dose at Completion of the Study
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Table 4
Equivalence Analysis for the Change in HbA1c(%) in the PP and ITT Analysis Set
jkda-30-466-i005
Table 5
Fasting Plasma Glucose and Postprandial (2 hr) Glucose in the ITT Analysis Set
jkda-30-466-i006
Table 6
Response Rates at Study End in the ITT Analysis Set
jkda-30-466-i007

*HbA1c < 7.0% or FPG < 140 mg/dL

†HbA1c < 7.0% and FPG < 140 mg/dL

Table 7
Compliance (%) in the ITT Analysis Set
jkda-30-466-i008
Table 8
Frequency of Hypoglycemia
jkda-30-466-i009

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