Diabetes Metab J.  2013 Dec;37(6):465-474. 10.4093/dmj.2013.37.6.465.

Glycemic Effectiveness of Metformin-Based Dual-Combination Therapies with Sulphonylurea, Pioglitazone, or DPP4-Inhibitor in Drug-Naive Korean Type 2 Diabetic Patients

• Lee YK
• Song SO
• Kim KJ
• Cho Y
• Choi Y
• Yun Y
• Lee BW
• Kang ES
• Cha BS
• Lee HC

• KMID: 2174228
• DOI: http://doi.org/10.4093/dmj.2013.37.6.465

Abstract

BACKGROUND
This study compared the glycemic effectiveness of three metformin-based dual therapies according to baseline hemoglobin A1c (HbA1c) to evaluate the appropriateness of the guideline enforced by the National Health Insurance Corporation of Korea for initial medication of type 2 diabetes (T2D).
METHODS
This prospective observational study was conducted across 24 weeks for drug-naive Korean T2D patients with HbA1c greater than 7.5%. Subjects were first divided into three groups based on the agent combined with metformin (group 1, gliclazide-modified release or glimepiride; group 2, pioglitazone; group 3, sitagliptin). Subjects were also classified into three categories according to baseline HbA1c (category I, 7.5%< or =HbA1c<9.0%; category II, 9.0%< or =HbA1c<11.0%; category III, 11.0%< or =HbA1c).
RESULTS
Among 116 subjects, 99 subjects completed the study, with 88 subjects maintaining the initial medication. While each of the metformin-based dual therapies showed a significant decrease in HbA1c (group 1, 8.9% to 6.4%; group 2, 9.0% to 6.6%; group 3, 9.3% to 6.3%; P<0.001 for each), there was no significant difference in the magnitude of HbA1c change among the groups. While the three HbA1c categories showed significantly different baseline HbA1c levels (8.2% vs. 9.9% vs. 11.9%; P<0.001), endpoint HbA1c was not different (6.4% vs. 6.6% vs. 6.0%; P=0.051).
CONCLUSION
The three dual therapies using a combination of metformin and either sulfonylurea, pioglitazone, or sitagliptin showed similar glycemic effectiveness among drug-naive Korean T2D patients. In addition, these regimens were similarly effective across a wide range of baseline HbA1c levels.

Keyword

Diabetes mellitus, type 2; Metformin; Pioglitazone; Sitagliptin; Sulphonylurea

MeSH Terms

Diabetes Mellitus, Type 2
Humans
Korea
Metformin
National Health Programs
Prospective Studies
Sitagliptin Phosphate
Metformin

Figure

• 

  Fig. 1 Flow of the study. A total of 116 patients were enrolled, and 99 subjects were analyzed in the study. Of these patients, 28 in the glimepiride/metformin group, 27 in the pioglitazone/metformin group, and 33 in the sitagliptin/metformin group completed the study without medication change. GI, gastrointestinal.

• 

  Fig. 2 Change in hemoglobin A1c (HbA1c) from baseline to 24 weeks. Solid lines indicate the median HbA1c level, and broken lines indicate the median of individually assessed differences in HbA1c level from baseline. Multiple linear regression was used for statistical analysis, and group I was used as a reference group. The change of HbA1c was not statistically different among groups at 12 weeks (group II, P=0.101; group III, P=0.673) or 24 weeks (group II, P=0.066; group III, P=0.678) after adjustment for baseline age, sex, body mass index, and baseline HbA1c level.

• 

  Fig. 3 (A) The proportions of individuals who achieved hemoglobin A1c (HbA1c) level ≤7% at 24 weeks, and (B) the proportions of individuals with overall successful diabetes control according to medication. (A) Dark gray bar indicates the proportion of individuals who achieved an HbA1c level ≤7% among those who did not change medications by the end of the study. Fisher exact test was used to compare the three groups, and there was no significant difference (P=0.649). (B) Light gray bar indicates the proportion of individuals, among the total number of subjects who initially enrolled in the study, except for those who did not continue with follow-up observation, who achieved an HbA1c level ≤7% at 24 weeks or reduced medication during the study period because of a very good response. The Fisher exact test was used to compare the three groups, and there was no significant difference (P=0.593).

• 

  Fig. 4 Change in hemoglobin A1c (HbA1c) according to baseline HbA1c level. Dark gray bar indicates the level at baseline and light gray bar at 24 weeks. Bars represent medians (low quartile, high quartile). Despite different initial HbA1c levels (8.2% vs. 9.9% vs. 11.9%; P<0.001), HbA1c level in each category after 24 weeks of treatment demonstrated no statistical difference by Kruskal-Wallis test (6.4% vs. 6.6% vs. 6.0%; P=0.051).

• 

  Fig. 5 (A) The proportions of individuals who achieved an hemoglobin A1c (HbA1c) level ≤7% at 24 weeks, and (B) the proportions of individuals with overall successful diabetes control according to baseline HbA1c level. Category I, 7.5%≤HbA1c<9.0; category II, 9.0%≤HbA1c<11.0; category III, 11.0%≤ HbA1c. (A) Dark gray bar indicates the proportion of individuals who achieved an HbA1c level ≤7% among those who did not change medications by the end of the study. Fisher exact test was used to compare the three groups, and there was no significant difference (P=1.000). (B) Light gray bar indicates the proportion of individuals, among the total number subjects who initially enrolled in the study, except for those who did not continue with follow-up observation, who achieved an HbA1c level ≤7% at 24 weeks or reduced medication during the study period because of a very good response. Fisher exact test was used to compare the three groups, and there was no significant difference (P=0.819).

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