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Abstract
Objectives
To evaluate the efficacy and predictive factors of Dipeptidyl peptidase-4 (DPP-4) inhibitors in type 2 diabetes mellitus (T2DM) patients who were not well controlled with other oral antidiabetic drugs or insulin in real clinical practice.
Methods
From December 2012 to January 2014, retrospective longitudinal observation study was conducted for patients with T2DM who were not reached a glycemic target (glycated hemoglobin [HbA1c] > 6.5%) with other oral antidiabetic drugs or insulins. Type 1 diabetes or other types of diabetes were excluded. Responders were eligible with decreased HbA1c from baseline for more than 5% during follow up period.
Results
Of total 135 T2DM patients having an average 9.0 months follow-up period, 84 (62.2%) of patients were responder to DPP-4 inhibitors. After concomitant treatment with DPP-4 inhibitors, patients had a mean decrease in HbA1c of 0.69 ± 1.3%, fasting plasma glucose of 13 ± 52 ㎎/㎗, and postprandial plasma glucose of 29 ± 85 ㎎/㎗ from baseline (all P< 0.05). Independent predictive factor for an improvement of glycemic control with DPP-4 inhibitors was higher baseline HbA1c (odds ratio 2.07 with 95% confidence interval 1.15–3.72) compared with non-responders.
Conclusions
A clinical meaningful improvement in glycemic control was seen when DPP-4 inhibitors were added to other anti-diabetic medications in patients with T2DM regardless of age, duration of T2DM, type of combination treatment regimen. Patients who had higher HbA1c were more easily respond to DPP-4 inhibitors treatment in short-term follow-up period.
References
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Fig. 1.
The efficacy of glycemic control after add-on treatment with DPP-4 inhibitors stratified by concomitant combination treatment. Values in the box represent the mean HbA1c level. ∗ P – value < 0.005 by paired t-test.
Table 1.
Baseline characteristics of the study subjects and changes of glycemic control after add-on reatment with DPP-4 inhibitors (N=135)
| Parameters | n | Baseline | Follow-up | P – value† |
|---|---|---|---|---|
| Age (years) | 135 | 56.9 (10.0) | ||
| Sex (M, %) | 135 | 82 (60.7) | ||
| BMI (kg/m2) | 135 | 25.1 (3.3) | ||
| SBP (mmHg) | 131 | 125 (15) | ||
| DBP (mmHg) | 130 | 72 (10) | ||
| Duration of diabetes (years) | 135 | 8.6 (7.3) | ||
| Laboratory findings | ||||
| FPG (mg/dl) | 105 | 148 (42) | 134 (41) | 0.019 |
| PP1 (mg/dl) | 111 | 247 (72) | 218 (68) | 0.002 |
| HbA1c (%) | 135 | 8.1 (1.2) | 7.4 (1.3) | < 0.001 |
| C-peptide (ng/ml) ∗ | 118 | 2.20 (1.62–2.98) | 2.09 (1.59–3.03) | 0.423 |
| Total cholesterol (mg/dl) | 133 | 183 (43) | 157 (31) | < 0.001 |
| Triglyceride (mg/dl) | 133 | 154 (93) | 135 (69) | 0.014 |
| HDL (mg/dl) | 133 | 48 (22) | 47 (14) | 0.864 |
| LDL (mg/dl) | 133 | 105 (34) | 90 (28) | < 0.001 |
| Creatinine (mg/dl) ∗ | 132 | 0.80 (0.69–0.95) | 0.82 (0.68–0.96) | 0.406 |
| uACR (ug/mg) ∗ | 128 | 16.3 (4.4–51.3) | 19.7 (9.4–58.3) | 0.765 |
| HOMA2-IR | 95 | 2.07 (1.16) | 2.00 (1.16) | 0.962 |
| HOMA2%B | 95 | 68.49 (43.30) | 70.72 (31.81) | 0.323 |
| Combination therapy | ||||
| Biguanide (n, %) | 135 | 123 (91.1) | ||
| Sulfonylurea (n, %) | 135 | 72 (53.3) | ||
| TZD (n, %) | 135 | 14 (10.4) | ||
| AGI (n, %) | 135 | 18 (13.3) | ||
| Insulin (n, %) | 135 | 22 (16.3) | ||
| Diabetes-related complications | ||||
| Retinopathy (n, %) | 135 | 42 (31.1) | ||
| Nephropathy (n, %) | 132 | 18 (13.6) | ||
| Neuropathy (n, %) | 135 | 34 (25.2) |
† analyzed by the paired t-test for normally distributed variables, and by the Wilcoxon signed rank test for continuous variables with skewed distributions.
BMI, body mass index; FPG, fasting plasma glucose; PP1, post-prandial 1-hr glucose; HbA1c, glycated hemoglobin;SBP, systolic blood pressure; DBP, diastolic blood pressure; HDL, high-density lipoprotein; LDL, low-density lipoprotein; uACR, spot urine albumin/creatinine ratio; TZD, thiazolidinedione; AGI, alpha-glucosidase inhibitor; HOMA2%B, homeostasis model assessment of pancreatic beta-cell function; HOMA2-IR, homeostasis model assessment of insulin resistance.
Table 2.
Baseline characteristics according to therapeutic response of DPP-4 inhibitor
| Characteristics | Responder | Non-responder | P – value† |
|---|---|---|---|
| n | 84 | 51 | |
| Age (years) | 57.1 (10.7) | 56.6 (8.9) | 0.792 |
| Sex (M/F) | |||
| BMI (kg/m2) | 24.9 (3.0) | 25.5 (3.8) | 0.267 |
| SBP (mmHg) | 123 (15) | 128 (16) | 0.069 |
| DBP (mmHg) | 72 (10) | 73 (10) | 0.640 |
| Duration of diabetes (months) | 7.8 (7.2) | 9.8 (7.3) | 0.118 |
| Follow-up duration (months) | 9.2 (1.8) | 8.6 (1.9) | 0.080 |
| FPG (mg/dl) | 154 (41) | 137 (41) | 0.047 |
| PP1 (mg/dl) | 245 (67) | 250 (79) | 0.700 |
| HbA1c (%) | 8.4 (1.2) | 7.7 (0.9) | 0.001 |
| C-peptide (ng/ml) ∗ | 2.33 (1.71–3.11) | 2.11 (1.54–2.73) | 0.172 |
| Total cholesterol (mg/dl) | 177 (39) | 194 (47) | 0.028 |
| TG (mg/dl) | 155 (92) | 152 (95) | 0.816 |
| HDL (mg/dl) | 46 (21) | 51 (23) | 0.259 |
| LDL (mg/dl) | 101 (35) | 112 (34) | 0.073 |
| Creatinine (mg/dl) ∗ | 0.81 (0.70–0.96) | 0.78 (0.65–0.95) | 0.112 |
| HOMA2%B | 66.15 (48.12) | 72.69 (33.20) | 0.437 |
| HOMA2-IR | 2.18 (1.27) | 1.88 (0.90) | 0.177 |
| Combination therapy | |||
| Metformin (n, %) | 76 (90.5) | 47 (92.2) | > 0.999 |
| Sulfonylurea (n, %) | 41 (48.8) | 31 (60.8) | 0.214 |
| TZD (n, %) | 11 (13.1) | 3 (5.9) | 0.249 |
| AGI (n, %) | 13 (15.5) | 5 (9.8) | > 0.999 |
| Insulin (n, %) | 8 (9.5) | 14 (27.5) | 0.008 |
† analyzed by the two-sample t-test for normally distributed variables, and by the Mann Whitney U-test for continuous variables with skewed distributions.
BMI, body mass index;SBP, systolic blood pressure; DBP, diastolic blood pressure; FPG, fasting plasma glucose; PP1, postprandial 1-hr glucose; HbA1c, glycated hemoglobin; TG, triglyceride; HDL, high-dense lipoprotein, HOMA2%B, homeostasis model assessment of pancreatic beta-cell function; HOMA2-IR, homeostasis model assessment of insulin resistance; TZD, thiazolidinedione; AGI, alpha-glucosidase inhibitor.
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