Safety and Efficacy of D-Tagatose in Glycemic Control in Subjects with Type 2 Diabetes

Abstract

The primary objectives of this study were to evaluate the treatment effect of D-tagatose on glycemic control, determined by a statistically significant decrease in hemoglobin A1c (HbA1c), and safety profile of D-tagatose compared to placebo. The secondary objectives were to evaluate the treatment effects on fasting blood glucose, insulin, lipid profiles, changes in BMI, and the proportion of subjects achieving HbA1c targets of <7%. Type 2 diabetic patients not taking any blood glucose lowering medications were administered either 15 g of D-tagatose dissolved in 125-250 ml of water three times a day or placebo with meals. Reduction in HbA1c was statistically significant compared to placebo at all post-baseline time points in the ITT population. Additionally, secondary endpoints were achieved in the ITT population with regard to LDL, total cholesterol, fasting blood glucose, and proportion of subjects achieving HbA1c targets of <7%. D-tagatose was unable to lower triglycerides or raise HDL compared to placebo. A subgroup LOCF analysis on the ITT US population showed a greater and statistically significant LS mean reduction in HbA1c in the D-tagatose group at all post-baseline visits. Based on these results it is concluded that in the ITT population D-tagatose is an effective single agent at treating many of the therapy targets of type 2 diabetes including lowering fasting blood glucose and HbA1c, and lowering of LDL and total cholesterol.

Keywords: Blood glucose; Cholesterol; HDL; HbA1c; Insulin; LDL; Triglycerides.

Figure 1

(A) Change in HbA1c in ITT population after 2 months of treatment. The primary efficacy endpoint set at 2 months in the ITT population showed a significant difference between placebo and D-tagatose groups (p=0.0198) (placebo n=182, D-tagatose n=172). (B) Change in HbA1c in ITT population. Significant differences were seen at 2 (p=0.0198), 4 (p=0.0160), 6 (p=0.0015), 8 (p=0.0002), and 10 months (p=<0.0001). (C) Change in HbA1c in PP population. Significant differences were seen at 6 (p=0.0343), 8 (p=0.0148), and 10 months (p=0.0021). Zero time points plotted as means, remaining time points plotted as least squares means ±SEM.

Figure 2

(A) Results of analyses for the ITT subgroup with starting HbA1c baseline < 7.5%. Significant differences between D-tagatose and placebo were seen at 6 (p=0.0030), 8 (p=0.0004), and 10 months (p=<0.0001). (B) Change in HbA1c in ITT subgroup with baseline >7.5%. A significant difference between D-tagatose and placebo was seen at 10 months (p=0.0277). (C) Change in HbA1c in PP subgroup with baseline HbA1c <7.5%, (D) Change in HbA1c in PP subgroup with baseline >7.5%. Zero time points plotted as means, remaining time points plotted as least squares means ±SEM.

Figure 3

(A) Change in HbA1c U.S. subjects, ITT population. (B) Change in HbA1c, Indian subjects, ITT population. (C) Change in HbA1c U.S. subjects, PP population. p-values for 2, 4, 6, 8, and 10 months of treatment are 0.0435, 0.0016, <0.0001, <0.0001, and <0.0001, respectively. (D) Change in HbA1c, Indian subjects, PP population. Zero time points plotted as means, remaining time points plotted as least squares means ±SEM.

Figure 4

(A) Change in fasting blood glucose, ITT population. D-tagatose significantly decreased fasting blood glucose compared to placebo after 6 months of treatment. (B) Change in fasting blood glucose levels, PP population. No significant difference between placebo and D-tagatose groups was observed at any time point. Zero time points plotted as means, remaining time points plotted as least squares means ±SEM.

Figure 5

(A) Total cholesterol, ITT population. (B) Total cholesterol, PP population. (C) LDL, ITT population. (D) LDL, PP population. (E) HDL, ITT population. Significant differences between D-tagatose and placebo were seen at 2 (p=0.0126), 4 (p=0.00040, 6 (p=0.0002), 8 (p=0.0003), and 10 months (p=0.0008). (F) HDL, PP population. The only significant difference was at 4 months (p=0.0397). Zero time points plotted as means, remaining time points plotted as least squares means ±SEM.

Figure 6

Serum triglycerides. (A) ITT population. (B) PP population. Zero time points plotted as means, remaining time points plotted as least squares means ±SEM.